[Dyspnea and cardia cancer, an unusual etiology]. / Epanchement péricardiaque : une cause peu ordinaire de dyspnée dans le décours d'une néoplasie du cardia.

CASE REPORT: a 63-year old man, followed for a metastatic cardia cancer, develop a pericardial effusion with sign of pre-tamponade. A CT scanner suggests the presence of a gastro- esophageal-pericardial fistula. A surgical drainage brings a purulent fluid, infected by a polymicrobial flora. Despite early antibiotics with vancomycin and piperacillin-tazobactam, the patient dies five days after the drainage. DISCUSSION: purulent pericarditis associated with gastrointestinal neoplasia may be due to sepsis or a proximity invasion . The diagnosis is based on ultrasound and pericardiocentesis. The most commonly involved organism is Streptococcus pneumoniae. The treatment involves intravenous antibiotics, pericardial drainage and intrapericardial instillation of antibiotics. The mortality rate remains high, especially in cases associated with gastrointestinal neoplasia.

Cas clinique : un patient de 63 ans, suivi pour une néoplasie du cardia généralisée, développe un épanchement péricardique associé à des signes de pré-tamponnade. Le CT scanner suggère la présence d'une fistule oeso- péricardique. Le drainage ramène un liquide purulent, et les analyses montrent une flore polymicrobienne. Malgré une antibiothérapie intraveineuse précoce par vancomycine et pipéracilline-tazobactam, le patient décède cinq jours après le drainage. DISCUSSION: les péricardites purulentes associées aux néoplasies digestives peuvent être secondaires à une septicémie ou à une atteinte de proximité. Le diagnostic est basé sur l'échographie cardiaque et la ponction du liquide péricardique. Le germe le plus fréquemment impliqué est le Streptococcus pneumoniae. Le traitement associe une antibiothérapie intra- veineuse, le drainage péricardique et l'instillation intrapéricardique d'antibiotiques. Le taux de mortalité reste élevé, particulièrement dans les cas associés aux néoplasies digestives.

Secukinumab: IL-17A inhibition to treat psoriatic arthritis.

Interleukin-17A is an important cytokine in the pathogenesis of psoriatic arthritis. Secukinumab is a recombinant, high-affinity, fully human immunoglobulin G1kappa monoclonal antibody with a selective binding and neutralization of interleukin-17A. By providing an alternative mechanism of action to current treatments, secukinumab has shown efficacy in the key clinical domains of psoriatic arthritis. In the present paper, we discuss the role of interleukin-17A as a clinically relevant target in the treatment of psoriatic arthritis, based on preclinical findings, dose-ranging and regimen-finding, randomized, placebo-controlled clinical trials.

Orbital wall infarction in child with sickle cell disease.

We present the case of a 17-year-old boy, known with homozygous sickle cell disease, who was admitted because of generalised pain. He developed bilateral periorbital oedema and proptosis, without pain or visual disturbances. In addition to hyperhydration, oxygen and analgesia IV antibiotics were started, to cover a possible osteomyelitis. Patients with sickle cell disease are at risk for vaso-occlusive crises, when the abnormally shaped red blood cells aggregate and block the capillaries. Such a crisis typically presents at a location with high bone marrow activity, as the vertebrae and long bones. At an early age, the bone marrow is still active at other sites, for example the orbital wall, and thus infarction can also occur there. Thus, in young persons with sickle cell disease, it is important to consider orbital wall infarction in the differential diagnosis, since the approach is different from osteomyelitis. If the disease is complicated by an orbital compression syndrome, corticosteroids or surgical intervention may be necessary to preserve the vision. In our patient, an MRI of the orbitae demonstrated periorbital oedema with bone anomalies in the orbital and frontal bones, confirming orbital wall infarction. Ophthalmological examination revealed no signs of pressure on the nervus opticus. The patient recovered gradually with conservative treatment.

The haptoglobin phenotype influences the risk of cutaneous squamous cell carcinoma in kidney transplant patients.

BACKGROUND: Cutaneous squamous cell carcinoma (SCC) is the most frequent skin cancer after organ transplantation. Currently, the pre-identification of transplant patients at increased risk for non-melanoma skin cancer remains difficult. OBJECTIVE: To investigate the Hp polymorphism as a marker for the identification of a subset of patients with an increased susceptibility to develop SCC/Bowen's disease. METHODS: Haptoglobin phenotyping was performed with haemoglobin-supplemented starch gel electrophoresis in 300 kidney transplant patients. High-performance gel permeation chromatography was used in case of low serum haptoglobin concentration. RESULTS: Cox regression analysis (adjusted for age, gender and Mediterranean origin) showed a significant association of the Hp 1-1 phenotype with a higher risk of SCC/Bowen's disease (P = 0.035) and multiple primary SCCs (P = 0.002). No significant difference between the Hp phenotypes was found for the development of Bowen's disease and SCCs in the first 10 years following renal transplantation. However, after a follow-up of >10 years, a significant association between the Hp 1-1 phenotype and the occurrence of Bowen's disease and SCC was reported (P = 0.002 and P = 0.001 respectively). CONCLUSIONS: This study shows an increased risk for the development of (multiple) SCCs in kidney transplant patients with the Hp 1-1 phenotype. This finding points to the role of Hp 1-1 phenotype as an important predictor in identifying a subset of patients with an increased need for preventive measures and is in agreement with the decreased anti-inflammatory capacity of this phenotype.

Spinal cord stimulation in the treatment of chronic critical limb ischemia.

This paper reviews the clinical experience and proposed working mechanisms of spinal cord stimulation (SCS) in the treatment of chronic critical limb ischemia (CCLI). SCS appears to provide a significant long-term relief of ischemic pain and to improve healing of small ulcers, most likely due to effects on the nutritional skin blood flow. Despite these observations, randomized trials were not able to show limb salvage. Assessment of the microcirculatory skin blood flow, by means of transcutaneous oxygen pressure measurements and videocapillaromicroscopy, is necessary to evaluate the remaining microcirculatory reserve capacity likely to be exploited by SCS and to help identify patients that will benefit most from this treatment and in whom stimulation could lead to limb salvage.

Systemic and local antibiotic prophylaxis in the prevention of prosthetic vascular graft infection: an experimental study.

AIM: to determine if local, in addition to systemic antibiotic prophylaxis (compared to that provided by systemic prophylaxis alone) provides additional benefit in terms of reducing graft infection. METHODS: gelatin-sealed Dacron grafts were interposed in the infrarenal aorta of 36 mongrels and inoculated with 1 ml of a S. aureus suspension. Group 1 (control group) received no prophylaxis and were inoculated with 1 ml containing 10(9)cfu/ml. Group 2 (n=6) received systemic prophylaxis (1 g cephamandole) and were inoculated with 10(5) cfu/ml (n=3) or 10(7) cfu/ml (n=3). Group 3 received systemic prophylaxis (1 g cephamandole) and were inoculated with 109 cfu/ml. Group 4 received systemic prophylaxis (2 g cephamandole) and were inoculated with 10(9)cfu/ml. In group 5 and 6 grafts were soaked in a rifampicin solution before use and inoculated with 10(9) cfu/ml. Group 5 received no systemic prophylaxis and group 6 received systemic prophylaxis (1 g cephamandole). Grafts were harvested at 2 weeks, and peritonitis, perigraft abscess, anastomotic disruption and graft occlusion recorded. Swabs were taken of the graft, the perigraft tissues and the peritoneal fluid. Graft segments were incubated in broth medium. RESULTS: inoculation with 10(9) cfu/ml ensured graft infection. Systemic or local prophylaxis alone failed to prevent graft infection. Only systemic and local antibiotic prophylaxis provided significant better results than no prophylaxis at all (p<0.01) and local prophylaxis alone (p<0.05). However, total "graft sterility" was not achieved as bacteriologic analysis of the graft segments showed low bacterial counts (<10 bacteria/graft) in 5 of 6 grafts. CONCLUSION: local and systemic prophylaxis provided more protection as demonstrated by the significant decrease in the incidence of "overt" graft infection. Total "graft sterility" cannot be expected in the case of an overwhelming bacterial challenge.

Fast determination of haptoglobin phenotype and calculation of hemoglobin binding capacity using high pressure gel permeation chromatography.

A new and fast method for haptoglobin (Hp) phenotyping was developed based on high pressure gel permeation chromatography of hemoglobin-supplemented serum. Haptoglobin phenotypes 1-1, 2-1, and 2-2 are resolved on the difference in size of their hemoglobin-haptoglobin complexes. Results are available in less than 15 min. Results of the chromatographic typing correspond to those obtained by conventional starch gel electrophoresis. Next to the phenotyping of haptoglobin, the method allows reproducible calculation of the hemoglobin binding capacity (HBC) of human serum. Using this methodology, reference values for HBC were found to be 0. 75+/-0.25 g/l, with the lowest HBC in Hp 2-2 subjects and the highest in Hp 1-1 subjects (P<0.05). In contrast to earlier findings, the ratio HBC:Hp concentration was found to be comparable for the three Hp types. In conclusion, this method allows a rapid phenotyping in critical clinical conditions where Hp phenotyping can be useful, e.g. determining the donor's phenotype in liver transplantation.

Associations between haptoglobin polymorphism, lipids, lipoproteins and inflammatory variables.

The haptoglobin allele frequencies and the phenotype distribution were determined in 741 male Caucasian workers, aged 35 to 59 years. The association of the haptoglobin polymorphism with various clinical and biochemical parameters was investigated. Furthermore a possible interaction with the apo E polymorphism on lipid and lipoprotein traits was analysed. The frequency of Hp1 and Hp2 was found to be 0.401 and 0.599, respectively. The observed distribution of Hp types (Hp 1-1, 15.5%; Hp 2-1, 49.3%; Hp 2-2, 35.2%) was in Hardy-Weinberg equilibrium. Age, body mass index, smoking, alcohol intake and blood pressure were comparable between the three Hp groups. Subjects with Hp 2-2 had significantly higher serum total and free cholesterol concentration compared to those in other haptoglobin types (P = 0.006 and P = 0.003). Similarly, apo B levels were significantly higher among Hp 2-2 individuals (P = 0.02). No significant differences were demonstrated between the Hp phenotypes in HDL cholesterol, apo A-I, apo E, Lp(a), cholesteryl esters, fibrinogen and C-reactive protein concentrations, although for the latter an increase was noticed in Hp 2-2. The effects of Hp type and apo E type on Lp(a) and on free cholesterol levels were found to be significantly multiplicative, with the highest free cholesterol values observed in subjects having Hp 2-2 and the apo epsilon4 allele. Significantly lower Lp(a) levels were observed in individuals carrying Hp 1-1 and an epsilon2 allele than in subjects without the epsilon2 allele. In conclusion, haptoglobin polymorphism may play an important role in the regulation of lipoprotein metabolism and could contribute to the risk of coronary heart disease. Larger samples are needed to clarify the clinical relevance of the gene-gene (Hp-apo E) interaction on lipids and lipoproteins.

Monitoring of median nerve somatosensory evoked potentials in carotid surgery.

The purpose of this study was to compare median somatosensory evoked potentials (SEP) in patients undergoing carotid endarterectomy (CEA) with routine shunting and nonshunting (excluding the option of selective shunting) and to evaluate the significance of a decrease in the amplitude of the cortically generated waveforms of the SEP and/or an increase in the central conduction time (CCT) on the one hand, and that of a loss of the cortical SEP, on the other. Somatosensory evoked potentials were recorded in 32 patients before, during, and after CEA with routine shunting or nonshunting. The N13 and N20 latency, the CCT, and the N20/P25 amplitude were evaluated. In addition, a meta-analysis of 15 previous studies was performed comprising a total of 3,136 patients. The intraoperative cortical SEP showed no differences between shunted and nonshunted patients, apart from the preclamping value of the N20/P25 amplitude which was lower in the nonshunted subjects. The number of patients with decreased and/or delayed cortical SEP (findings frequently used as criterion for selective shunting) was similar in the two study groups. A loss of the cortical SEP occurred in one patient operated on without an indwelling shunt. None of these patients had a new neurologic deficit after surgery. In the meta-analysis, the positive predictive value of decreased and/or delayed cortical SEP was extremely poor, that of absent cortical SEP was poor to moderate and the prevalence of new neurologic deficits was similar in patients undergoing CEA with routine shunting-nonshunting and those with selective shunting-nonshunting. Our study suggests that decreased and/or delayed cortical SEP are unreliable predictors of the neurological outcome of CEA patients and consequently an unsuitable criterion for selective shunting. The meta-analysis confirms this finding and shows that the neurologic outcome is not improved by using an indwelling shunt selectively based on SEP monitoring.

Improvement of microcirculatory blood flow under epidural spinal cord stimulation in patients with nonreconstructible peripheral arterial occlusive disease.

Epidural spinal cord stimulation (ESCS) has been suggested as a method to improve microcirculatory blood flow and to reduce the amputation rate in vascular patients. We studied the effects of ESCS on microcirculatory blood flow in 237 patients with nonreconstructible peripheral arterial occlusive disease. Clinical status was classified as Fontaine Stage 3 (ischemic rest pain) in 169 patients and as Fontaine Stage 4 (ulcers/gangrene) in 68 patients. After a mean follow-up period of 31.2 months, major pain relief (> 75%) was noticed in patients who retained their limbs. Sixty-four patients underwent major amputation despite ESCS. Clinical improvement was confirmed by the increase in transcutaneous oxygen (TcPO2).

Thromboembolic complications in a patient with heparin-induced thrombocytopenia (HIT) showing cross-reactivity to a low molecular weight heparin-treatment with Org 10172 (Lomoparan).

Heparin-induced thrombocytopenia is an immuno-mediated life-threatening side effect of heparin therapy which poses difficulties in diagnosis and major therapeutic problems. Heparin must be instantly discontinued. We describe the case of a 60-year-old male patient with type II heparin-induced thrombocytopenia, complicated by progressive deep venous thrombosis and pulmonary embolism. He failed to improve when therapy was continued with a low molecular weight heparin (Fragmin) and high doses of intravenous immunoglobulins were administered. The test for heparin-dependent platelet aggregation was positive for unfractionated heparin and low molecular weight heparin, but negative for the heparinoid Org 10172. During subsequent anticoagulant therapy with Org 10172 for seven days the number of platelets increased rapidly and the patient recovered. Nine months later Org 10172 was used again in this patient for thrombosis prophylaxis without any adverse effects. In patients with heparin-induced thrombocytopenia requiring immediately acting anticoagulant therapy, Org 10172 can be considered as an effective alternative drug to unfractionated and low molecular weight heparins.

[Abdominal aortic aneurysm: surgery, indications, technique, outcome]. / Das abdominelle Aortenaneurysma: Operation, Indikation, Technik, Ergebnisse.

The fate of a patient with an abdominal aortic aneurysm] (AAA) is influenced by the risk of rupture and embolism. When the indication for operation is considered, individual associated risk factors have to be taken into account. With regard to the literature, the following recommendations concerning indication for surgery can be given: emergency surgery for symptomatic or ruptured aneurysm; elective surgery: aneurysms 5 cm diameter or growing AAA 5 mm/year, patient with acceptable individual risk for operation; asymptomatic aneurysms less than 5 cm in diameter, without growth in patients aged over 75 years and/or considerable perioperative risk should not be operated on: sonography should be done 3-monthly as a continuing control. Finally the results in our institution are presented for elective surgery: 30-day mortality 3.5%, AAA with rupture, no shock: 20%, ruptured AAA with shock 47%, respectively.