Category Archives: Original Research

Persistent Ductus Arteriosus in Critically Ill Preterm Infants

Maria Livia Ognean1*, Oana Boantă1, Simona Kovacs2, Corina Zgârcea1, Raluca Dumitra1, Ecaterina Olariu1, Doina Andreicuţ2

1 Neonatology I, Clinical County Emergency Hospital Sibiu, Romania
2 Neonatology II-Premature Infants, Clinical County Emergency Hospital Sibiu, Romania

DOI: 10.1515/jccm-2016-0026

Introduction: Persistent ductus arteriosus (PDA) is found with increased incidence in preterm infants, significantly affecting neonatal morbidity and mortality rates.
Aim: To evaluate the association between the presence of PDA and the severity of clinical condition at birth in critically ill preterm infants, with gestational ages (GA) ≤ 32 weeks and severe respiratory distress.
Methods: All preterm infants with GA ≤ 32 weeks admitted to the neonatal intensive care unit (NICU) of the Clinical County Emergency Hospital, Sibiu between 1 January 2010 and 31 December 2015 were included in the study. These were categorized as Group 1 [Preterm infants with PDA; n=154] and Group 2 [Preterm infants without PDA; n=186]. Epidemiological and clinical data were collected in the National Registry for Respiratory Distress Syndrome for all children, and data related to prenatal period, clinical characteristics at birth i.e GA, weight, gender, Apgar scores, and clinical features such as resuscitation at birth, surfactant administration, need and duration of respiratory support, neonatal sepsis, complications associated with prematurity, and death, were analyzed.
Results: Group 1 infants had significantly lower GA and birth weights, were more often out born (p=0.049, HR 1.69), and had significantly lower Apgar scores at 1 and 10 minutes (p=0.022, p=0.000). They presented a significantly higher need for surfactant administration (42.9% vs 24.7%, p<0.0001) and respiratory support (96.8% vs 90.3%, HR 3.19, p=0.019 for need of CPAP and 22.1% vs 10.8%, HR 2.35, p=0.004 for mechanical ventilation). Duration of respiratory support was also significantly higher in the Group 1 (7.6%±7.5 vs. 5.1±3.8 days, p<0.0001 for CPAP and 20.1±22.5 vs. 12.0±15.7 days, p<0.0001 for mechanical ventilation).
Conclusion: In very preterm infants, PDA may be associated with a critical clinical condition leading to serious complications. The presence of PDA after the seventh day of life was associated with an increased need for respiratory support, both CPAP and mechanical ventilation, increased severity of the respiratory distress syndrome, requiring a longer duration of respiratory support, and increased the hospitalization length. In very preterm infants, PDA presence was also associated with a higher rate of severe complications and death, indicating the need for a careful and proper management of these critical cases in neonatal intensive care units.

Keywords: , , , ,
Full text: PDF

Can APACHE II, SOFA, ISS, and RTS Severity Scores be Used to Predict Septic Complications in Multiple Trauma Patients?

Sebastian Trancă1, Cristina Petrișor1, Natalia Hagău1, Constantin Ciuce2

1 Department of Anaesthesia and Intensive Care II, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Romania
2 Surgical Department I, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Romania

DOI: 10.1515/jccm-2016-0019

Background: Physiological composite scores are used to predict mortality in multiple trauma patients. Sepsis is the leading cause of late mortality in trauma victims brought about by immune suppression due to homeostasis dysregulation.
Objective: To determine whether APACHE II, SOFA, ISS and RTS scores can predict the occurrence of sepsis in multiple trauma patients.
Methods: APACHE II, SOFA, ISS, and RTS scores were calculated during the first twenty-four hours after the injury for sixty-four adult poly-traumatic patients. The occurrence of infectious complications was investigated over a fourteen-day period. The infection-free rates for the multiple trauma patients were considered as end-points in the Kaplan-Meier plot analysis.
Results: For SOFA, a cutoff score of 4 points was identified as a predictor of the occurrence of sepsis, with 89% of the patients with SOFA<4 being infection-free, while 37% of those with SOFA>4 were infection-free (p<0.01). None of the patients with APACHE II≤5 points developed infections. Eighty-four percent of patients with APACHE II scores of 5-10 did not develop sepsis, while 49% with APACHE II≥11 were infection-free (p<0.01).  A cutoff of 7 points was found to be most discriminative for RTS. Eighty-eight percent of the patients with RTS≥7 and 43% of those with RTS<7 were infection-free (p<0.01). Eighty-eight percent of patients with ISS<22 did not develop sepsis and 56% with ISS≥22 did not develop sepsis (p<0.01).
Conclusion: APACHE II, SOFA, ISS, and RTS functional severity scores can predict mortality as well as the occurrence of sepsis in multiple trauma patients.

Keywords: , ,
Full text: PDF

Influence of Ventilation Parameters on Intraabdominal Pressure

Claudiu Puiac1, Janos Szederjesi1*, Alexandra Lazar1, Emoke Almasy1, Paul Rad1, Lucian Puscasiu2

1 Anesthesiology Department, University of Medicine and Pharmacy of Tirgu Mures, Romania
2 Gynecology and Obstetrics Department, University of Medicine and Pharmacy of Tirgu Mures, Romania

DOI: 10.1515/jccm-2016-0016

Introduction: Intraabdominal pressure monitoring is not routinely performed because the procedure assumes some invasiveness and, like other invasive procedures, it needs to have a clear indication to be performed. The causes of IAH are various. Mechanically ventilated patients have numerous parameters set in order to be optimally ventilated and it is important to identify the ones with the biggest interference in abdominal pressure. Although it was stated that mechanical ventilation is a potential factor of high intraabdominal pressure the set parameters which may lead to this diagnostic are not clearly named.
Objectives: To evaluate the relation between intraabdominal pressure and ventilator parameters in patients with mechanical ventilation and to determine the correlation between intraabdominal pressure and body mass index.
Material and method: This is an observational study which enrolled 16 invasive ventilated patients from which we obtained 61 record sheets. The following parameters were recorded twice daily: ventilator parameters, intraabdominal pressure, SpO2, Partial Oxygen pressure of arterial blood. We calculated the Body Mass Index (BMI) for each patient and the volume tidal/body weight ratio for every recorded data point.
Results: We observed a significant correlation between intraabdominal pressure (IAP) and the value of PEEP (p=0.0006). A significant statistical correlation was noted regarding the tidal volumes used for patient ventilation. The mean tidal volume was 5.18 ml/kg. Another significant correlation was noted between IAP and tidal volume per kilogram (p=0.0022). A positive correlation was found between BMI and IAP (p=0.0049), and another one related to the age of the enrolled patients. (p=0.0045).
Conclusions: The use of positive end-expiratory pressures and high tidal volumes during mechanical ventilation may lead to the elevation of intraabdominal pressure, a possible way of reducing this risk would be using low values of PEEP and also low volumes for the setting of ventilation parameters. There is a close positive correlation between the intraabdominal pressure levels and body mass index.

Keywords: , ,
Full text: PDF

Intubation-Surfactant: Extubation on Continuous Positive Pressure Ventilation. Who Are the Best Candidates?

Maria Livia Ognean1*, Silvia-Maria Stoicescu2, Oana Boantă1, Leonard Năstase2,
Carmen Gliga3, Manuela Cucerea3,4

1 Clinical County Emergency Hospital Sibiu, Neonatology Department
2 University of Medicine and Pharmacy Carol Davila Bucuresti, Institute of Mother and Child Care – Polizu, Neonatology Department
3 Clinical County Emergency Hospital Târgu Mureș, Regional Neonatal Intensive Care Center
4 University of Medicine and Pharmacy Târgu Mureș

DOI: 10.1515/jccm-2016-0010

Introduction: Respiratory distress syndrome (RDS) continues to be the leading cause of illness and death in preterm infants. Studies indicate that INSURE strategy (INtubate-SURfactant administration and Extubate to nasal continuous positive airway pressure [nCPAP]) is better than mechanical ventilation (MV) with rescue surfactant, for the management of respiratory distress syndrome (RDS) in very low birth weight (VLBW) neonates, as it has a synergistic effect on alveolar stability.
Aim of the study: To identify the factors associated with INSURE strategy failure in preterm infants with gestational age (GA) ≤ 32 weeks.
Materials and Methods: This was a retrospective cohort study, based on data collected in the Romanian National Registry for RDS patients by three regional (level III) centers between 01.01.2010 and 31.12.2011. All preterm infants of ≤ 32 weeks GA were included. Prenatal and neonatal information were compared between (Group 1), the preterm infants successfully treated using INtubation-SURfactant-Extubation on nasal CPAP (INSURE) strategy and (Group 2 ), those who needed mechanical ventilation within seventy-two hours after INSURE.
Results: A total of 637 preterm infants with GA ≤ 32 weeks were included in the study. INSURE strategy was performed in fifty-seven cases (8.9%) [ Group 1] and was successful in thirty-one patients (54.4%). No differences were found as regards the studied prenatal and intranatal characteristics between (Group 1) and Group 2 who needed mechanical ventilation. Group 2 preterm infants who needed mechanical ventilation within 72 hours after INSURE had significantly lower mean Apgar scores at 1 and 5 minutes and lower peripheral oxygen saturation (SpO2) during resuscitation at birth (p<0.05). Successful INSURE strategy was associated with greater GA, birth weight (BW), fraction of inspired oxygen (FiO2) during resuscitation, and an increased mean dose of surfactant but these associations were not statistically significant (p>0.5).
Conclusion: In preterm infants ≤ 32 weeks gestation, increased INSURE failure rates are associated with complicated pregnancies, significantly lower Apgar scores at 1 and 5 minutes, and lower peripheral oxygen saturation during resuscitation.

Keywords: , , ,
Full text: PDF

Total Intravenous Versus Inhalation Anesthesia in Patients Undergoing Laparoscopic Cholecystectomies. Effects on Two Proinflammatory Cytokines Serum Levels: Il-32 and TNF-Alfa.

Adina Hadade1*, Daniela Ionescu1, Teodora Mocan2, Alexandru Necula3, Victor Cristea4

1 Department of Anesthesia and Intensive Care, “IuliuHatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
2 Department of Physiology, “IuliuHatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
3 Department of Surgery, Regional Institute for Gastroenterology and Hepatology “Prof dr Octavian Fodor”, Cluj-Napoca, Romania
4 Department of Clinical Immunology, “IuliuHatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

DOI: 10.1515/jccm-2016-0008

Introduction: It has been reported that as compared with total intravenous anesthesia (TIVA), inhalation anesthesia is increasing the postoperative level of proinflammatory interleukins.
The aim of the study is to investigate if there is an in-vivo relationship between proinflammatory cytokines, Interleukin-32 (IL-32) and Tumour necrosis factor – α (TNF- α), in patients undergoing laparoscopic cholecystectomies with two different anesthetic techniques, TIVA or inhalation anesthesia.
Material and Methods: Twenty two consecutive patients undergoing laparoscopic cholecystectomies were prospectively randomized into two groups: Group 1: TIVA with target-controlled infusion (TIVA-TCI) (n=11) and Group 2: isoflurane anesthesia (ISO) (n=11). IL-32 and TNF-α were determined before the induction of anesthesia (T1), before incision (T2) and at 2h (T3) and 24h (T4) postoperatively. Our primary outcome was to compare plasma levels of IL-32 and TNF- α concentrations (expressed as area-under-the-curve) over 24 hours between study groups. Our secondary outcome was to establish whether there is a correlation between plasma levels of IL-32 and of TNF-α at each time point between the two groups.
Results: Area-under-the-curve (AUC) of IL-32 plasma concentration was 7.53 in Group 1 (TIVA) versus 3.80 in Group 2 (ISO), p= 1. For TNF-α, AUC of plasma concentration was 733.9 in Group 1 (TIVA) and 668.7 in Group 2 (ISO), p= 0.066. There were no significant differences in plasma concentrations of both IL-32 and TNF- α between the groups.
Conclusions: IL-32 expression in response to minor surgery is very low. There were no significant difference between plasma levels ofTNF- α and IL-32 after TIVA versus inhalation anesthesia during the first 24 hours postoperatively. Further studies are needed on larger groups to investigate whether there can be a correlation between these interleukins after 2 different anesthetic techniques and the impact of this correlation on postoperative outcome.

Keywords: , , ,
Full text: PDF

Factors Favouring the Development of Clostridium Difficile Infection in Critically Ill Patients

Bianca-Liana Grigorescu1, Raluca Ştefania Fodor1*, Adrian Dan Cioc2, Mihaly Veres2, Monica Orlandea2, Bogdan Lăzescu2, Emoke Almasy2

1 University of Medicine and Pharmacy of Tîrgu Mureş, 38 Gheorghe Marinescu street Tîrgu Mureş, 540139, Romania
2 County Clinical Emergency Hospital Tîrgu Mureş, Romania, 50 Gheorghe Marinescu street Tîrgu Mureş, 540139, Romania

DOI: 10.1515/jccm-2016-0006

Clostridium difficile, an anaerobic, spore-forming, toxin-forming, gram-positive bacillus present in the bacterial flora of the colon is the principal cause of nosocomial diarrhoea in adults.
Aim: Assessment of favouring factors of Clostridium difficile infections as well as the interactions between them, in critically ill hospitalized patients undergoing complex medical and surgical treatments.
Material and Methods: A retrospective case-control study involving eighty patients admitted in the Intensive Care Unit (ICU) of the County Clinical Emergency Hospital Tîrgu-Mureş was conducted between January and October 2014. Patients aged eighteen years and over, who had undergone complex medical and surgical treatment, were divided into two subgroups. Group 1 included patients who developed diarrhoea but were not diagnosed as having a Clostridium difficile infection (CDI). Group 2 included patients who developed diarrhoea due to CDI as indicated by a positive culture and the expression of exotoxin. The assessed parameters were age, length of stay (LOS), antibiotic spectrum, association with proton pump inhibitors (PPI) or H2-receptor antagonists, immunological status, the presence or lack of gastrointestinal tract surgery.
Results: The mean age was 64.6 years with an average LOS of 10 days. Fifty-six percent of patients came to the ICU from internal medicine wards and forty-three percent from surgical wards. 20.5% of them were immunosuppressed. Co-association of ceftriaxone and pantoprazole significantly increased the risk of CDI compared to co-administration of any other antibiotic or pantoprazole (p=0.01). The odds ratio for Pantoprazole together with any antibiotic versus antibiotic therapy alone was significantly higher (p=0.018) with a sevenfold increase in the risk of positive exotoxin increase.
Conclusions: Antibiotic use is associated with “no risk to develop CDI” in the first five days of administration. PPIs associated therapy increased the risk of CDI in first seventy-two hours regardless of the antibiotic type, and contributes to an active expression of CD exotoxin.

Keywords: , , ,
Full text: PDF

Recent Advances Of Mucosal Capnometry And The Perspectives Of Gastrointestinal Monitoring In The Critically Ill. A Pilot Study

Péter Palágyi1*, Sándor Barna2, Péter Csábi3, Péter Lorencz1, Ildikó László1, Zsolt Molnár1

1 Department of Anaesthesiology and Intensive Therapy, University of Szeged, Hungary
2 Department of Anaesthesiology and Intensive Therapy, Bács-Kiskun County Hospital, Teaching Hospital of the University of Szeged, Hungary
3 Department of Anaesthesia and Intensive Care, Wexham Park Hospital, United Kingdom

DOI: 10.1515/jccm-2016-0002

Mucosal capnometry involves the monitoring of partial pressure of carbon dioxide (PCO2) in mucous membranes. Different techniques have been developed and applied for this purpose, including sublingual or buccal sensors, or special gastrointestinal tonometric devices. The primary use of these procedures is to detect compensated shock in critically ill patients or patients undergoing major surgery. Compensatory mechanisms, in the early phases of shock, lead to the redistribution of blood flow towards the vital organs, within ostensibly typical macro-haemodynamic parameters. Unfortunately, this may result in microcirculatory disturbances, which can play a pivotal role in the development of organ failure. In such circumstances mucosal capnometry monitoring, at different gastrointestinal sites, can provide a sensitive method for the early diagnosis of shock. The special PCO2 monitoring methods assess the severity of ischaemia and help to define the necessary therapeutic interventions and testing of these monitors have justified their prognostic value. Gastrointestinal mucosal capnometry monitoring also helps in determining the severity of ischaemia and is a useful adjunctive in the diagnosis of occlusive splanchnic arterial diseases. The supplementary functional information increases the diagnostic accuracy of radiological techniques, assists in creating individualized treatment plans, and helps in follow-up the results of interventions. The results of a pilot study focusing on the interrelation of splanchnic perfusion and gastrointestinal function are given and discussed concerning recent advances in mucosal capnometry.

Keywords: , , , , ,
Full text: PDF

Predictors Of Mortality In Patients With ST-Segment Elevation Acute Myocardial Infarction And Resuscitated Out-Of-Hospital Cardiac Arrest

Andreea Bărcan, Monica Chițu*, Edvin Benedek, Nora Rat, Szilamer Korodi, Mirabela Morariu, Istvan Kovacs

University of Medicine and Pharmacy of Tirgu Mureș, Romania, Department of Internal Medicine, Clinic of Cardiology

DOI: 10.1515/jccm-2016-0001

Introduction: In patients with out-of-hospital cardiac arrest (OHCA) complicating an ST-segment elevation myocardial infarction (STEMI), the survival depends largely on the restoration of coronary flow in the infarct related artery. The aim of this study was to determine clinical and angiographic predictors of in-hospital mortality in patients with OHCA and STEMI, successfully resuscitated and undergoing primary percutaneous intervention (PCI).
Methods: From January 2013 to July 2015, 78 patients with STEMI presenting OHCA, successfully resuscitated, transferred immediately to the catheterization unit and treated with primary PCI, were analyzed. Clinical, laboratory and angiographic data were compared in 28 non-survivors and 50 survivors.
Results: The clinical baseline characteristics of the study population showed no significant differences between the survivors and non-survivors in respect to age (p=0.06), gender (p=0.8), the presence of hypertension (p=0.4), dyslipidemia (p=0.09) obesity (p=1), smoking status (p=0.2), presence of diabetes (p=0.2), a clinical history of acute myocardial infarction (p=0.7) or stroke (p=0.17). Compared to survivors, the non-survivor group exhibited a significantly higher incidence of cardiogenic shock (50% vs 24%, p=0.02), renal failure (64.3% vs 30.0%, p=0.004) and anaemia (35.7% vs 12.0%, p=0.02). Three-vessel disease was significantly higher in the non-survivor group (42.8% vs. 20.0%, p=0.03), while there was a significantly higher percentage of TIMI 3 flow postPCI in the infarct-related artery in the survivor group (80.% vs. 57.1%, p=0.03). The time from the onset of symptoms to revascularization was significantly higher in patients who died compared to those who survived (387.5 +/- 211.3 minutes vs 300.8 +/- 166.1 minutes, p=0.04), as was the time from the onset of cardiac arrest to revascularization (103.0 +/- 56.34 minutes vs 67.0 +/- 44.4 minutes, p=0.002). Multivariate analysis identified the presence of cardiogenic shock (odds ratio [OR]: 3.17, p=0.02), multivessel disease (OR: 3.0, p=0.03), renal failure (OR: 4.2, p=0.004), anaemia (OR: 4.07, p=0.02), need for mechanical ventilation >48 hours (OR: 8.07, p=0.0002) and a duration of stay in the ICU longer than 5 days (OR: 9.96, p=0.0002) as the most significant independent predictors for mortality in patients with OHCA and STEMI.
Conclusion: In patients surviving an OHCA in the early phase of a myocardial infarction, the presence of cardiogenic shock, renal failure, anaemia or multivessel disease, as well as a longer time from the onset of symptoms or of cardiac arrest to revascularization, are independent predictors of mortality. However, the most powerful predictor of death is the duration of stay in the ICU and the requirement of mechanical ventilation for more than forty-eight hours.

Keywords: , , ,
Full text: PDF

Plasma Neutrophil Gelatinase Associated Lipocalin (NGAL) – Early Biomarker for Acute Kidney Injury in Critically Ill Patients

Raluca Fodor1, Bianca Grigorescu2*, Mihaly Veres2, Monica Orlandea2, Judita Badea2, Katalin Hlavathy2, Adrian Cioc2

1 Department of Anaesthesiology and Intensive Care, University of Medicine and Pharmacy, Tirgu Mures, Romania
2 Department of Anaesthesiology and Intensive Care, Emergency County Hospital, Tirgu Mures, Romania

DOI: 10.1515/jccm-2015-0023

Introduction: NGAL (Neutrophil Gelatinase Associated Lipocalin) is a biomarker recently introduced into clinical practice for the early diagnosis of acute kidney injury (AKI). The aim of this study was to correlate the plasmatic NGAL value determined at admission with clinical progression and severity of AKI in critically ill patients.
Material and method: Thirty two consecutive critically ill adult patients at risk of developing AKI (trauma, sepsis), admitted in Intensive Care Unit of the Clinical County Emergency Hospital Mures, between January to March 2015 were enrolled in the study. For each patient included in the study plasma NGAL levels were determined on admission, and these were correlated with the degree of AKI development (according to AKIN criteria) at 48 hours and 5 days post admission. The discriminatory power of NGAL, creatinine, creatinine clearance and corrected creatinine (depending on water balance) were determined using the ROC (receiver-operating characteristic) and likelihood ratios.
Results: ROC curve analysis showed a better discriminatory capacity in terms of early diagnosis of AKI for NGAL (AUC=0.81 for NGAL, AUC=0.59 for creatinine, AUC=0.62 for corrected creatinine, AUC=0.29 for creatinine clearance). The value of likelihood ratio was also significantly higher for NGAL (3.01±2.73 for NGAL, 1.27±1.14 for creatinine, 1.78±1.81 for corrected creatinine, and 0.48±0.33 for creatinine clearance).
Conclusions: NGAL biomarker has a better discrimination capacity for early prediction of acute kidney injury compared to previously used markers.

Keywords: , , ,
Full text: PDF

An Evaluation of Serum Procalcitonin and C-Reactive Protein Levels as Diagnostic and Prognostic Biomarkers of Severe Sepsis

Janos Szederjesi1*, Emoke Almasy1, Alexandra Lazar1, Adina Huțanu2, Iudita Badea1, Anca Georgescu3

1 Department of Anesthesiology and Intensive Care, University of Medicine and Pharmacy Tirgu Mures, Romania
2 County Clinical Emergency Hospital Tirgu Mures, Romania
3 Department of Infectious Diseases, University of Medicine and Pharmacy Tirgu Mures, Romania

DOI: 10.1515/jccm-2015-0022

Background: Recommendations have been made, following the multicenter Surviving Sepsis Campaign study, to standardize the definition of severe sepsis with reference to several parameters such as haemodynamic stability, acid-base balance, bilirubin, creatinine, International Normalized Ratio (INR), urine output and pulmonary functional value of the ratio between arterial oxigen partial pressure and inspiratory oxigen concentration. Procalcitonin (PCT) is considered to be a gold standard biomarker for the inflammatory response, and recent studies have shown that it may help to discover whether a seriously ill person is developing sepsis. C-reactive protein (CRP) is also used as a marker of inflammation in the body, as its blood levels increase if there is any inflammation in the body.
The aim of this study was to evaluate serum procalcitonin and C-reactive protein levels as diagnostic and prognostic biomarkers of severe sepsis.
Material and method: Sixty patients, diagnosed as being “septic”, were admitted to the intensive care unit (ICU). Based on laboratory results and clinical findings a diagnosis of “severe sepsis“ was made, and correlated with PCT and CRP values. The APACHE II, SAPS II and SOFA severity scores were calculated, analyzed and correlated with PCT and CRP.
Results: Fifty two patients (86.67%) presented with criteria for severe sepsis. Multivariate correlation analysis indicated a significant positive association between procalcitonin and all severity scores (APACHEII p<0.0001, SOFA p<0.0001, SAPS II p<0.0001). CRP proved to be significantly correlated only with the SAPS II score (p=0.0145). Mortality rate was high, with 48 patients (80%) dying. There was no significant correlation between the levels of the PCT and CRP biomarkers and severe sepsis (p=0.2059 for PCT, p=0.6059 for CRP).
Conclusions: The procalcitonin levels are highly correlated with the severity scores (APACHE II, SAPS II, SOFA) regularly used in ICUs and therefore can be used for determining the severity of the septic process. Quantitive procalcitonin and C-reactive protein analysis was not shown to be useful in diagnosing severe sepsis. However, PCT and CRP can be used to predict the fatal progression of the septic patient.

Keywords: , , ,
Full text: PDF