Preoperative use of epoietin beta in total hip replacement: a prospective study

Objective

Epoietin (EPO) effectively decreases perioperative blood transfusion requirements. We evaluated the feasibility of using EPO beta to increase haemoglobin levels before total hip replacement (THR) and reduce transfusion.

Materials and methods

One hundred and seventy-one patients undergoing primary THR were included in this prospective observational study. Patients with initial haemoglobin level <130 g l^?1 received EPO beta subcutaneously in a four-dose regimen. Haemoglobin levels were measured at baseline, before surgery, and at postoperative days 1 and 5.

Results

Twenty-eight patients received EPO beta preoperatively, 143 were not treated including 42 with initial haemoglobin level <130 g l^?1. Haemoglobin increased by 29 ± 9 g l^?1 in the low Hb + EPO group versus 2 ± 1 g l^?1 for the other patients. In the low Hb + EPO group 3.6% were transfused, in the low HB group 45.2% (P = 0.001) and in the normal Hb group 11.9% (P = 0.2).

Conclusions

Preoperative EPO beta increases haemoglobin level and reduces transfusion frequency in anaemic patients before total joint replacement. It could play a major role in the management of perioperative blood loss in orthopaedic surgery.     

Interscalene brachial plexus block for glenohumeral luxation in prehospital medicine

We report the case of a successful interscalene block for the pain management of a glenohumeral luxation in prehospital care. Interscalene block is an attractive technique in prehospital pain management. However, this regional anaesthesia technique must be performed only by a skilled anaesthesiologist.     

Assessment of renal function in clinical practice at the bedside of burn patients

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * In burn patients it has been shown ([2]), that there is a correlation between the creatinine clearance (CL(CR)) and the clearance of inulin. * The CL(CR) has never been studied in burn patients who have normal serum creatinine. * The Robert, Kirkpatrick and sMDRD formulae have never been evaluated in burn patients. WHAT THIS STUDY ADDS: * Despite burn patients having normal serum creatinine concentrations, the study showed that there are large variations in CL(CR) which cannot be detected by single serum creatinine measurements, and which have important implications for drug therapy. * It showed that the formulae currently used to calculate creatinine clearance on the basis of serum creatinine are inadequate for use in burn patients, and they should be abandoned in favour of direct measurement from a 24 h urine collection. AIMS: The aim of this study was to evaluate whether the renal function of burn patients could be correctly assessed using a single serum creatinine measurement, within normal limits, and three prediction equations of glomerular filtration taking into account, serum creatinine, age, weight and sex. METHODS: This was a prospective study comprising 36 adult burn patients with a serum creatinine <120 micromol l(-1), within the second or third week following the burn injury. Renal function was assessed using serum creatinine, 24 h urinary CL(CR), and the Cockcroft-Gault, Robert, Kirkpatrick and simplified MDRD equations. RESULTS: Despite normal serum creatinine concentrations in all patients, a significant number had a decreased CL(CR). The urinary CL(CR) was <80 ml(-1) min(-1) 1.73 m(-2) in nine patients (25%), and <60 ml(-1) min(-1) 1.73 m(-2) in five patients (14%). Between the groups having a CL(CR) lower or greater than 80 ml(-1) min(-1) 1.73 m(-2) there were no differences in gender, burn indices, percentage of mechanically ventilated patients or length of hospital stay, but a difference in age. The highest CL(CR) (>140 ml(-1) min(-1) 1.73 m(-2)) was found in 13 patients younger than 40 years. Regression analysis, residual and Bland-Altman plots revealed that neither the Cockcroft-Gault, Robert, Kirkpatrick nor sMDRD equations were specific enough for the assessment of renal function. CONCLUSIONS: In burn patients with normal serum creatinine during the hypermetabolic phase, serum creatinine and creatine based predictive equations are imprecise in assessing renal function.     

Intermittent administration of ceftazidime to burns patients: influence of glomerular filtration

OBJECTIVE: The pharmacokinetics of ceftazidime, the antibiotic of choice for treating acute P. aeruginosa infections, may be modified in burns patients. The aim of this study was to identify the factors causing variations in the serum antibiotic concentrations in bums patients. METHODS: 30 patients with serious burns were randomly divided into two groups. Group 1 received a dose of ceftazidime of 2 x 3 g/24 hours. The second group received the same dose but divided into 6 administrations. Blood samples were taken at 24 (M1) and 48 hours (M2) after the start of treatment and the peak and trough serum concentrations of ceftazidime measured by HPLC. Depending on the results, frequency and/or dose was modified to obtain trough concentrations (Cmin) equal to 16 mg/l, i.e. 4 times the MIC. Either the same dose was maintained, but mostly divided up, or it was increased to 1 g x 8 administrations or it was decreased to 1 g x 4 or 1 g x 3. The serum concentrations of ceftazidime obtained were analyzed taking into account the characteristics of the burns patients (multivariate correlation). RESULTS: From the first sample (M1) Cmin was lower than the target concentration in 50% of the patients in Group 1 and 20% in Group 2. The modification of the dosing regimen put into place after the first analysis, led to the patients being further divided into four groups before the second blood sampling. Finally, 5 patients ended up in Group 1. In all patients and for all administration times, a negative correlation was found between Cmin and the creatinine clearance, calculated by using Cockcroft's formula. CONCLUSION: This study highlights the peculiarities of ceftazidime pharmacokinetics seen in burns patients with high interindividual variability. Based on Cmin monitoring and a predefined therapeutic range, dose adjustment was often required. Ceftazidime clearance is correlated with creatinine clearance (Cockcroft's formula), suggesting that this parameter could be used for a priori or a posteriori dose individualization. To respect the summary of the product characteristics (SPC) and reduce the variability in trough concentrations, the dose should be fractionated (1 g x 6) over a 24-hour period or even given as a continuous infusion. Trough concentrations must be evaluated to adapt the dosage regimen to attain target concentrations of 4 x the MIC.     

CD8(+) T cells specific for tumor antigens can be rendered dysfunctional by the tumor microenvironment through upregulation of the inhibitory receptors BTLA and PD-1

Cytotoxic T cells that are present in tumors and capable of recognizing tumor epitopes are nevertheless generally impotent in eliciting tumor rejection. Thus, identifying the immune escape mechanisms responsible for inducing tumor-specific CD8(+) T-cell dysfunction may reveal effective strategies for immune therapy. The inhibitory receptors PD-1 and Tim-3 are known to negatively regulate CD8(+) T-cell responses directed against the well-characterized tumor antigen NY-ESO-1. Here, we report that the upregulation of the inhibitory molecule BTLA also plays a critical role in restricting NY-ESO-1-specific CD8(+) T-cell expansion and function in melanoma. BTLA-expressing PD-1(+)Tim-3(-) CD8(+) T cells represented the largest subset of NY-ESO-1-specific CD8(+) T cells in patients with melanoma. These cells were partially dysfunctional, producing less IFN-γ than BTLA(-) T cells but more IFN-γ, TNF, and interleukin-2 than the highly dysfunctional subset expressing all three receptors. Expression of BTLA did not increase with higher T-cell dysfunction or upon cognate antigen stimulation, as it does with PD-1, suggesting that BTLA upregulation occurs independently of functional exhaustion driven by high antigen load. Added with PD-1 and Tim-3 blockades, BTLA blockade enhanced the expansion, proliferation, and cytokine production of NY-ESO-1-specific CD8(+) T cells. Collectively, our findings indicate that targeting BTLA along with the PD-1 and Tim-3 pathways is critical to reverse an important mechanism of immune escape in patients with advanced melanoma.     

Left Ventricular-Right Atrial Communication with Third-degree Atrioventricular Block after Thoracic Trauma

Background

Intracardiac shunts are rare but very serious lesions after non-penetrating chest trauma. Their diagnosis is difficult. This pathology often goes unrecognized in the context of multiple trauma.

Case Report

We report the case of a 21-year-old man involved in a motor vehicle crash who presented with multiple injuries including myocardial contusion, severe brain injury, multiple pelvic fractures, closed femur fracture, bilateral lung contusion with a right pneumothorax, and intra-abdominal injuries. Three days after the initial event, a new cardiac murmur and complete heart block appeared. Transthoracic echocardiography (echo) followed by transesophageal echo revealed a high-velocity flow communication between the left ventricle and the right atrium. The patient underwent delayed cardiac surgery due to other unstable injuries. The hospital course was prolonged but favorable, and the patient left the hospital 1 month later without any neurologic or cardiologic after-effect.

Conclusion

This case highlights the potential for cardiac complications to occur in any patient with serious thoracic trauma. Transesophageal echo should be performed on any trauma patient with electrocardiographic abnormalities.     

Sustained stimulation and expansion of Tregs by IL2 control autoimmunity without impairing immune responses to infection,vaccination and cancer

Interleukin 2 (IL2) is the key cytokine supporting survival and function of regulatory T cells (Tregs). We recently reported that low-dose IL2 safely expands/stimulates Tregs and improves autoimmune conditions in humans. Further development of IL2 in autoimmune diseases will require chronic IL2 administration, which could affect beneficial effector immune responses regulated by Tregs. We used recombinant adeno-associated viral vector (rAAV)-mediated gene transfer to continuously release IL2 in mice and assessed its long-term effects on immune responses. A single rAAV-IL2 injection enabled sustained stimulation and expansion of Tregs without inducing Teff activation and prevented diabetes in NOD mice. After several weeks of IL2 production, mice responded normally to a viral challenge and to vaccination, and had pregnancies with offspring that developed normally. They showed no change in the occurrence and growth of chemically-induced tumors. Altogether, chronic low-dose IL2 treatment does not affect beneficial effector immune responses at doses that prevent autoimmune diabetes.