Category Archives: Original Research

New Targets for End-Stage Chronic Kidney Disease Therapy

Niki Prakoura, Panos Kavvadas, Christos Chatziantoniou

Inserm UMR S 1155 and University Pierre et Marie Curie, Paris,  France

DOI: 10.1515/jccm-2015-0015

Severe forms of chronic kidney disease can lead to a critical, end-stage condition, requiring renal replacement therapy, which may involve a form of dialysis or renal transplantation. Identification and characterization of novel markers and/or targets of therapy that could be applied in these critically ill patients remains the focus of the current research in the field of critical care medicine and has been the objective of our studies for some years past. To this end, we used models of renal vascular disease, Ang II, L-NAME or mice overexpressing renin, treated with AT1 antagonists at different stages of progression, to create cohorts of animals during progression, reversal or escape from therapy. Transcriptomic analysis and comparisons were performed and genes were selected according to the following criteria: a) not previously described in the kidney, b) highly upregulated during progression and returning to the normal levels during reversal, and c) producing proteins that are either circulating or membrane receptors.
The involvement of the selected genes in the mechanisms of renal disease was confirmed in additional models of renal disease, initiated in other compartments of the kidney such as glomeruli (administration of nephrotoxic serum) or the tubular interstitium (unilateral ureteral obstruction). The potential of the therapy was tested using mice lacking the expression of these genes and by in vivo administration of antisense oligonucleotides which blocked the transcription of the targeted genes. This strategy allowed the identification of periostin, an extracellular matrix protein normally involved in bone and tooth development, in addition to the discoidin domain receptor1 (DDR1) as potential targets of therapy against renal inflammation and fibrosis.

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Residual Curarization and Postoperative Respiratory Complications Following Laparoscopic Sleeve Gastrectomy. The Effect of Reversal Agents: Sugammadex vs. Neostigmine

Tiberiu Ezri1,4, Shmuel Evron1,4, Irina Petrov1, Pinhas Schechter2, Yitzhak Berlovich3, Mordechai Shimonov2

The Departments of Anesthesia1, Surgery2 and Management3, The Edith Wolfson Medical Center, Holon, Israel and Outcomes Research Consortium,4 Holon, Israel

DOI: 10.1515/jccm-2015-0009

Background: Incomplete muscle relaxant reversal or re-curarization may be associated with postoperative respiratory complications. In this retrospective study we compared the incidence of postoperative residual curarization and respiratory complications in association with the type of muscle relaxant reversal agent, sugammadex or neostigmine, in patients undergoing laparoscopic sleeve gastrectomy.
Material and methods: We reviewed the charts of all patients (179) undergoing laparoscopic sleeve gastrectomy from July 2012 to July 2013 at Wolfson Medical Center. Sugammadex 1.5-2 mg/kg (112 patients) or neostigmine 2.5 mg (67 patients) were used as reversal agents. Results were compared by the type of reversal agent employed. Compared parameters included demographic and anaesthetic data, residual curarization, oxyhemoglobin saturation (SpO2) in the recovery room (PACU), episodes of SpO2 lower than 90% in PACU, unexpected intensive care (ICU) admissions, incidence of atelectasis and pneumonia, re-intubation and duration of hospitalization.
Results: Obstructive sleep apnea syndrome (OSAS) was more frequent in the sugammadex group (19% vs. 8%; p = 0.026). Total intravenous anesthesia (TIVA) was more frequently associated with sugammadex (33% vs. 16%; p = 0.007). There were no differences in postoperative residual curarization, SpO2 < 90% episodes, reintubation, ICU admissions, pulmonary complications and duration of hospitalization.
Conclusion: With the inherent limitations of a retrospective study, the use of sugammadex following laparoscopic sleeve gastrectomy showed no advantage over neostigmine in terms of residual curarization and respiratory complications.

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The Role of Angiopoietine-2 in the Diagnosis and Prognosis of Sepsis

Janos Szederjesi1, Emoke Almasy1, Alexandra Lazar1, Adina Huțanu2, Anca Georgescu3

1 University of Medicine and Pharmacy Tîrgu Mureş, Romania, Discipline of Intensive Care, 38 Gheorghe Marinescu street, Tirgu Mures, 540139, Romania
2 County Clinical Emergency Hospital Tirgu Mures, Romania, 50 Gheorghe Marinescu street Tirgu Mures, 540139, Romania
3 University of Medicine and Pharmacy Tîrgu Mureş, Romania, Discipline of Infectious Diseases, 38 Gheorghe Marinescu street, Tirgu Mures, 540139, Romania

DOI: 10.1515/jccm-2015-0004

Introduction: Angiopoietin-2 (ANG-2) is a new biomarker whose blood-serum values increase in sepsis and its expression is elevated in line with the severity of the degree of inflammation. The aim of this study was to identify the diagnostic role of ANG-2 in patients with non-surgical sepsis addmitted to an intensive care unit.
Material and methods: This was a prospective randomized study including 74 patients admitted in the Clinic of Intensive Care of the County Clinical Emergency Hospital Tirgu Mureș, divided into two groups: Group S: patients with sepsis (n=40, 54%) and Group C: control, without sepsis (n=34, 46%). ANG-2 levels were determined in both groups.
Results: From the Group S, 14 patients (35%) had positive haemocultures. ANG-2 values varied between 1 and 43 ng/mL, with an average of 6.0 ng/mL in patients without sepsis and 10.38 ng/mL in patients with sepsis (p=0.021). A positive correlation between ANG-2 and SAPS II, SOFA and APACHE II severity scores was demonstrated, as was a positive correlation between serum levels of ANG-2 and procalcitonine. ANG-2 had a 5.71% specificity and 74.36% sensitivity for diagnosis of sepsis.
Conclusions: ANG-2 serum levels were elevated in sepsis, being well correlated with PCT values and prognostic scores. ANG-2 should be considered as a useful biomarker for the diagnosis and the prognosis of this pathology.

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The Value of the “Lab-Score” Method in Identifying Febrile Infants at Risk for Serious Bacterial Infections

Diana Aniela Moldovan1,2, Maria Despina Baghiu1,3, Alina Balas2, Sorana Teodora Truta1,2

1 University of Medicine and Pharmacy of Tirgu Mures, Gheorghe Marinescu street no.38, Tirgu Mures, 540139, Romania

2 Tîrgu Mures County Clinical Emergency Hospital, Emergency Department, Gheorghe Marinescu street no.50, Tirgu Mures, 540136, Romania

3 Tîrgu Mures Emergency Clinical County Hospital, Paediatric Clinic, Gheorghe Marinescu street no.50, Tirgu Mures, 540136, Romania

DOI: 10.1515/jccm-2015-0003

Introduction: Most children with fever without source will have a self limited viral infection though a small percent will develop a serious bacterial infection (SBI) like urinary tract infection, pneumonia, bacteraemia, meningitis or sepsis. The challenge facing practitioners is to distinguish between these two groups and currently biomarkers, like C-reactive protein (CRP) and Procalcitonin (PCT), are available for this purpose.
The aim of the current study was to identify SBI in infants with fever without an identifiable cause using the recently introduced “Lab-score” combining C-reactive protein, procalcitonin and urine dipstick results.
Methods: This survey is part of an observational study aimed at identifying children with fever without source at risk of SBI. Patients were recruited from the Emergency Department of Tîrgu Mures Emergency Clinical County Hospital, Romania, during 2013. SBI diagnosis was based on urine, blood and cerebrospinal fluid cultures and chest radiographs. For infants, aged 7 days to 12 months, CRP and PCT were determined and the “Lab-score” was calculated. Positive and negative likelihood ratios and post test probabilities were calculated for each parameter and score.
Results: Of the ninety infants included in the study, SBI was diagnosed in nineteen (21.11%). Ten had a urinary tract infection, seven had pneumonia, one had a urinary tract infection and bacteraemia, and one had sepsis. Positive and negative likelihood ratios for CRP (≥40.0 mg/L) and PCT (≥0.5 ng/mL) were 10.27/0.45 and 7.07/0.24 and post-test probabilities 73%/65%. For a “Lab-score” (≥3), positive and negative likelihood ratios were 10.43/0.28, and the post-test probability was 73%.
Conclusions: In our survey the “Lab-score” proved a strong predictor for the identification of febrile infants at risk of SBI, but showed no significant difference compared with CRP and PCT which both proved equally good predictors for SBI.

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