Impact of graft preservation solutions for liver transplantation on early cytokine release and postoperative organ dysfunctions. A pilot study.

INTRODUCTION: During liver transplantation, graft ischemia-reperfusion injury leads to a systemic inflammatory response producing postoperative organ dysfunctions. The aim of this observational and prospective study was to compare the impact of Solution de conservation des organes et tissus (SCOT) 15 and University of Wisconsin (UW) preservation solutions on early cytokine release, postreperfusion syndrome and postoperative organ dysfunctions. METHODS: Thirty-seven liver transplantations were included: 21 in UW Group and 16 in SCOT 15 group. Five cytokines were measured in systemic blood after anesthetic induction, 30minutes after unclamping portal vein and on postoperative day 1. RESULTS: Following unclamping portal vein, cytokines were released in systemic circulation. Systemic cytokine concentrations were higher in UW than in SCOT 15 group: Interleukin-10, Interleukine-6. In SCOT 15 group, significant reduction of postreperfusion syndrome incidence and acute kidney injury were observed. Alanine and aspartate aminotransferase peak concentrations were higher in SCOT 15 group than in UW group. However, from postoperative day 1 to day 10, aminotransferase returned to normal values and did not differ between groups. CONCLUSIONS: Compared to UW, SCOT 15 decreases systemic cytokine release resulting from graft ischemia-reperfusion injury and reduces incidence of postreperfusion syndrome and postoperative renal failure.

Discontinuation of echinocandin and azole treatments led to the disappearance of an FKS alteration but not azole resistance during clonal Candida glabrata persistent candidaemia.

To give an indication of a fitness cost conferred by FKS mutation-associated echinocandin resistance in Candida glabrata during human infection. Six C. glabrata clinical strains sequentially isolated from blood and a hepatic abscess in a solid organ transplant recipient were analysed. The patient had received long-term azole and echinocandin therapy for invasive aspergillosis and persistent candidaemia. Minimal inhibitory concentrations were determined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) broth microdilution method. Molecular mechanisms of antifungal resistance were determined by sequencing hot spots of the FKS. Strain relatedness was determined using a microsatellite-based typing method. Typing analysis revealed an identical microsatellite pattern for all isolates, supporting a close relation. The first C. glabrata isolate showed wild-type phenotype (i.e. susceptibility to echinocandins and low level of azole resistance). After voriconazole therapy, the C. glabrata quickly acquired pan-azole resistance. Later, echinocandin treatment led to the emergence of a FKS2 S663P alteration and echinocandin resistance. After disruption of both azole and echinocandin therapy in favour of liposomal amphotericin B, C. glabrata isolates regained full susceptibility to echinocandin and lost the FKS2 S663P alteration while nonetheless maintaining their pan-azole resistance. Our clinical report supports the potential existence of a fitness cost conferred by FKS mutation in C. glabrata, as disruption of treatment led to a rapid disappearance of the resistant clone. This suggests that a more restricted use and/or a discontinuous administration of echinocandins may limit the spread of clinical resistance to this class.

Passive transient transfer of peanut allergy by liver transplantation.

We report a case of transient symptomatic transferred IgE-mediated peanut allergy after elective blood-group compatible liver transplantation. We show that the allergy was transient and therefore passive, authorizing further uneventful peanut consumption. Skin tests with commercial peanut extract and native peanut were performed in the recipient. Circulating specific IgE against peanut and recombinant peanut allergens (rArah1, rArah2, rArah3) was measured in stored serum samples collected from the recipient between 6 months before and 8 months after liver transplantation. Specific IgE levels in the donor were measured at the time of multiorgan donation. In the recipient, diagnosis of IgE-mediated peanut anaphylaxis was based on the clinical history and detection of specific IgE against peanut and recombinant major peanut allergens (rArah1, rArah2 and rArah3). Skin tests were negative and specific IgE undetectable 6 months after the clinical reaction. Oral peanut challenge was negative excluding persistent peanut allergy. This case confirms that IgE-mediated peanut allergy can be transferred by liver transplantation and shows that it may be transient and therefore passively acquired.

Fusidic acid induced acute immunologic thrombocytopenia.

Fusidic acid is used in hospitals as second-line therapy for multidrug-resistant staphylococcal infections. We report the first fully documented case of fusidic acid induced thrombocytopenia, in a 48-year-old patient. The thrombocytopenia was abrupt and severe but resolved spontaneously 7 d after drug withdrawal. The thrombocytopenia transiently relapsed 6 d later, when fusidic acid was reintroduced. Haemorrhagic signs were observed, but no severe bleeding occurred. Platelet transfusions failed to increase the platelet count. We detected an IgG platelet antibody in the patient's serum, that specifically recognized platelet glycoprotein IIb/IIIa only in the presence of fusidic acid. Fusidic acid induced thrombocytopenia should be considered as a possible cause for the thrombocytopenia frequently seen in the intensive care setting.

Dose-response curves of inhaled nitric oxide with and without intravenous almitrine in nitric oxide-responding patients with acute respiratory distress syndrome.

BACKGROUND: Inhaled nitric oxide, a selective pulmonary vasodilator, in combination with intravenous almitrine, a selective pulmonary vasoconstrictor, markedly improves arterial oxygenation in 50-60% of patients with acute lung injury. The goal of this study was to assess dose response of inhaled nitric oxide with and without almitrine in patients with acute respiratory distress syndrome responding to nitric oxide. METHODS: Six critically ill patients (aged 44 +/- 7 yr) were studied during early stage of their acute respiratory failure (Murray score: 2.6 +/- 0.1). All responded to 15 parts per million (ppm) of inhaled nitric oxide by an increase in Pao2 of at least 40 mmHg at FIo2 1. Hemodynamic and respiratory parameters were recorded continuously from pulmonary artery and systemic catheters. Inspiratory, expiratory, and mean intratracheal nitric oxide concentrations were monitored continuously using a fast response time chemiluminescence apparatus (NOX 4000, Sérès, Aix-en-provence, France). On day 1, 6 inspiratory concentrations of nitric oxide were randomly administered: 0.15, 0.45, 1.5, 4.5, 15, and 45 ppm to determine the dose response of inhaled nitric oxide on Pao2, pulmonary shunt, mean pulmonary artery pressure, and pulmonary vascular resistance index. On day 2, a continuous intravenous infusion of almitrine at a dose of 16 micrograms.kg-1.min-1 was administered and dose response to inhaled nitrix oxide was repeated according to the same protocol as during day 1. A constant FIo2 of 0.85 was used throughout the study. RESULTS: Nitric oxide induced a dose-dependent increase in Pao2 for inspiratory nitric oxide concentrations ranging between 0.15 and 1.5 ppm. Almitrine increased Pao2/FIo2 from 161 +/- 30 to 251 +/- 45 mmHg (P < 0.001) and pulmonary vascular resistance index from 455 +/- 185 to 527 +/- 176 dyn.s.cm-5.m2 (P < 0.05), and decreased pulmonary shunt (Qs/QT) from 35 +/- 2 to 33 +/- 3% (P < 0.001). During almitrine combined with nitric oxide, a dose-dependent increase in Pao2 was observed for inspiratory nitric oxide concentrations ranging between 0.15 and 1.5 ppm. Almitrine plus nitric oxide 1.5 ppm increased Pao2/FIo2 from 161 +/- 30 to 355 +/- 36 mmHg (P < 0.001), decreased Qs/QT from 35 +/- 2 to 24 +/- 2% (P < 0.001), pulmonary vascular resistance index from 455 +/- 185 to 385 +/- 138 dyn.s.cm-5.m2 (P < 0.05), and mean pulmonary artery pressure from 31 +/- 4 to 28 +/- 4 mmHg (P < 0.001). CONCLUSIONS: In 6 patients with early acute respiratory distress syndrome and highly responsive to inhaled nitrix oxide, the administration of intravenous almitrine at a concentration of 16 micrograms.kg-1.min-1 induced an additional increase in Pao2. Dose response of nitric oxide was not changed by the administration of almitrine and a plateau effect was observed at inspiratory nitric oxide concentrations of 1.5 ppm.

[Digestive manifestations of the acquired immunodeficiency syndrome (AIDS): study in 26 patients]. / Manifestations digestives du syndrome d'immunodéficience acquise (SIDA): étude chez 26 patients.

We studied the gastrointestinal manifestations in 26 cases of AIDS. The patients belonged to two different epidemiological groups: the first group included thirteen french homosexual men, the second group included 6 Haitians, 6 Africans and a Pakistanian, none of them admit homosexual activity. The clinical manifestations were: chronic watery diarrhea in 17 cases, bloody diarrhea in 2 cases; loss of weight in the 26 cases; dysphagia in five cases; jaundice in one patient (due to Kaposi sarcoma of the ampulla of Vater). The digestive lesions found, alone or associated, were necrotizing enteritis (2), ulcerative colitis (1), pseudomembranous colitis (1), Candida esophagitis (10), erythematous duodenitis (6), proctitis (4), Kaposi sarcoma (3), diffuse (2) or localized (1). Thirteen patients out of the 26 presented opportunistic digestive infections due to one or several germs. These were 10 cases of esophageal infection (due to Candida albicans) and 8 cases of enterocolonic infection due to Cytomegalovirus (3 cases), Cryptosporidium (3 cases), Mycobacterium avium intracellulare (1 case), Cryptococcus neoformans (1 case). The other digestive infections cases were due to non-opportunistic pathogens: Entamoeba histolytica (3 cases); Giardia lamblia (3 cases); Strongyloides stercoralis (2 cases); Salmonella typhi (2 cases); Shigella (1 case); Herpes simplex virus (1 case). No difference was noticed between the homosexual and the heterosexual groups with respect to the nature and the frequency of the digestive infections.