BACKGROUND
Etoricoxib is a selective inhibitor of cyclooxygenase 2 used mainly to treat osteoarticular pain. Here, we report the case of a patient who developed acute kidney failure and immune ...hemolytic anemia after the use of etoricoxib.
STUDY DESIGN AND METHODS
An 83‐year‐old female patient developed immune hemolytic anemia and acute kidney failure after treatment with etoricoxib for articular pain. Given the acute kidney failure, she required five hemodialysis sessions. She was discharged after 17 days. The case of immune hemolytic anemia and kidney failure was fully resolved.
RESULTS
The direct antiglobulin test was not only positive for IgG but also for C3b and C3d, showing a very intense reactivity (+++). The eluate's reactivity was weaker (++) and showed no defined specificity. The investigation of unexpected antibodies in the serum of the patient showed a reactivity pattern similar to the eluate's: weak reactivity without specificity. The serum of the patient was compared to urine and plasma samples of two groups of volunteers. The indirect antiglobulin test showed only a very strong reactivity with the urine samples of the volunteers who had received etoricoxib.
DISCUSSION
Considering that positive eluate is not the typical serologic profile of drug‐induced immune hemolytic anemia, developing in‐house techniques to show the causal link between them may be of interest to guide the treatment and avoid the empirical use of drugs.
CONCLUSION
Etoricoxib must be considered as a possible cause of acute kidney failure in cases of immune hemolytic anemia.
Background
A growing body of research shows a reciprocal regulation between the neural and immune systems. Acetylcholine (ACh) is the most important parasympathetic neurotransmitter, and increasing ...evidence indicates that it is able to modulate the immune response. Interestingly, in recent years, it has become clear that immune cells express a non‐neuronal cholinergic system, which is stimulated in the course of inflammatory processes. We have previously shown that dendritic cells (DC) express muscarinic receptors, as well as the enzymes responsible for the synthesis and degradation of ACh. Here, we analyzed whether ACh could also modulate the functional profile of DC.
Methods
Dendritic cells were obtained from monocytes cultured for 5 days with GM‐CSF+IL‐4 or isolated from peripheral blood (CD1c+ DC). The phenotype of DC was evaluated by flow cytometry, the production of cytokines was analyzed by ELISA or intracellular staining and flow cytometry, and the expression of muscarinic and nicotinic receptors was evaluated by flow cytometry or qRT‐PCR.
Results
Treatment of DC with ACh stimulated the expression of the Th2‐promoter OX40L, the production of the Th2‐chemokines MDC (macrophage‐derived chemokine/CCL22) and TARC (thymus and activation‐regulated chemokine/CCL17), and the synthesis of IL‐4, IL‐5, and IL‐13 by T cells, in the course of the mixed lymphocyte reaction (MLR). Moreover, we found that the stimulation of OX40L, HLA‐DR, and CD83 expressions in DC induced by the Th2‐promoting cytokine TSLP, as well as the production of IL‐13, IL‐4, and IL‐5 by T cells in the course of the MLR, was further enhanced when DC were treated with TSLP plus ACh, instead of TSLP or ACh alone.
Conclusions
Our observations suggest that ACh polarizes DC toward a Th2‐promoting profile.
Background
Maternal antigen‐presenting cells attracted to the pregnant uterus interact with trophoblast cells and modulate their functional profile to favour immunosuppressant responses. Non‐neuronal ...cholinergic system is expressed in human cytotrophoblast cells and in immune cells with homeostatic regulatory functions.
Aim
The aim of this work was to evaluate whether non‐neuronal acetylcholine conditions maternal monocyte and DC migration and activation profiles.
Methods
We used an in vitro model resembling maternal–placental interface represented by the co‐culture of human trophoblast cells (Swan‐71 cell line) and monocytes or DC.
Results
When cytotrophoblast cells were treated with neostigmine (Neo) to concentrate endogenous acetylcholine levels, monocyte migration was increased. In parallel, high levels of IL‐10 and decreased levels of TNF‐α were observed upon interaction of maternal monocytes with trophoblast cells. This effect was synergized by Neo and was prevented by atropine, a muscarinic acetylcholine receptor antagonist. Similarly, trophoblast cells increased the migration of DC independently of Neo treatment; however, enhanced IL‐10 and MCP‐1 synthesis in trophoblast–DC co‐cultures with no changes in TNF‐α and IL‐6 was observed. In fact, there were no changes in HLA‐DR, CD86 or CD83 expression. Finally, trophoblast cells treated with Neo increased the expression of two antigen‐presenting cells attracting chemokines, MCP‐1, MIP‐1α and RANTES through muscarinic receptors, and it was prevented by atropine.
Conclusions
Our present results support a novel role of acetylcholine synthesized by trophoblast cells to modulate antigen‐presenting cell migration and activation favouring an immunosuppressant profile that contributes to immune homeostasis maintenance at the maternal–foetal interface.
Introduction
To determine the effects of tranexamic acid (TXA) on transfusions in patients undergoing hip replacement with a hybrid or cementless prosthesis.
Methods
A group of 172 consecutive ...patients aged 18 years or older who underwent elective hip replacement with uncemented or hybrid prostheses, undergoing surgery between January 2012 and January 2014 by the same primary surgeon and anesthesiologist, were retrospectively included. TXA (1 g) was administered immediately before incision in the TXA group. Primary variables included number of red blood cell transfusions and the influence of TXA for each type of prosthesis. Secondary variables included hematocrit at discharge, length of hospital stay, thrombosis or pulmonary embolism, seizures, and death.
Results
Average transfusion was 1.53 units/patient in the control group compared to 0.6 units/patient in the TXA group (z = 6.29; U = 1640.5;
p
< 0.0001). TXA use was significantly correlated with the number of units transfused (
p
< 0.0001, 95% CI −1.24 to −0.68). Odds risk reduction for transfusion was observed during surgery (OR: 0.14; CI 0.06–0.29;
p
< 0.0001) and during the rest of hospital stay (OR: 0.11; CI 0.01–0.96;
p
= 0.046). Both hybrid and cementless prostheses that received TXA were transfused less than control groups (0.57 ± 1 vs. 1.7 ± 1
p
< 0.01 and 0.65 ± 1 vs. 1.24 ± 1
p
< 0.01). No difference was observed between the groups regarding adverse effects. Hematocrit values at discharge and length of hospital stay were similar between groups. No deaths were observed during hospital stay.
Conclusions
TXA reduced transfusions without increasing the prevalence of adverse effects. This reduction was observed during surgery and the following days of hospital stay for both for hybrid and cementless prosthesis.
BACKGROUNDEtoricoxib is a selective inhibitor of cyclooxygenase 2 used mainly to treat osteoarticular pain. Here, we report the case of a patient who developed acute kidney failure and immune ...hemolytic anemia after the use of etoricoxib. STUDY DESIGN AND METHODSAn 83-year-old female patient developed immune hemolytic anemia and acute kidney failure after treatment with etoricoxib for articular pain. Given the acute kidney failure, she required five hemodialysis sessions. She was discharged after 17 days. The case of immune hemolytic anemia and kidney failure was fully resolved. RESULTSThe direct antiglobulin test was not only positive for IgG but also for C3b and C3d, showing a very intense reactivity (+++). The eluate's reactivity was weaker (++) and showed no defined specificity. The investigation of unexpected antibodies in the serum of the patient showed a reactivity pattern similar to the eluate's: weak reactivity without specificity. The serum of the patient was compared to urine and plasma samples of two groups of volunteers. The indirect antiglobulin test showed only a very strong reactivity with the urine samples of the volunteers who had received etoricoxib. DISCUSSIONConsidering that positive eluate is not the typical serologic profile of drug-induced immune hemolytic anemia, developing in-house techniques to show the causal link between them may be of interest to guide the treatment and avoid the empirical use of drugs. CONCLUSIONEtoricoxib must be considered as a possible cause of acute kidney failure in cases of immune hemolytic anemia.
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