Syndrome de Cogan : à propos d'un cas et brève revue de la littérature [Cogan's Syndrome]

We report the case of a 20-year-old woman, with no medical history, who in a short period of time developed the association of a bilateral vestibulocochlear deficit and a nonsyphilitic interstitial keratitis, the usual clinical presentation of Cogan's syndrome. This rare disease was named after David Cogan, the ophthalmologist to whom we owe the description of the first series of cases. The precise aetiology of Cogan's syndrome has yet to be defined, but clinical and biological evidence point toward an immunopathological process. Some authors distinguish between a typical and an atypical form of Cogan's syndrome, the former being associated with interstitial keratitis, the latter with other forms of ocular involvement. The diagnosis of Cogan's syndrome is mainly a clinical one, the association of a bilateral vestibulocochlear deficit and a non-syphilitic keratitis being almost specific. Cogan's syndrome is frequently associated with general signs and cardiovascular, neurological, rheumathological and digestive involvement. Laboratory data usually show nonspecific inflammatory signs (elevation of the white cell count and of the erythrocyte sedimentation rate). The mortality of the disease is essentially determined by its cardiovascular involvement, mostly aortic insufficiency, which should therefore actively be sought for in every patient. It is useful to emphasise that the typical form of Cogan's syndrome carries a higher risk regarding the development of aortic insufficiency, whereas the atypical form is more often associated with a systemic vasculitis. Treatment is mandatory, based upon corticosteroids, and must sometimes be intensified by the administration of a steroid-sparing immunosuppressive drug. Although our patient perfectly met the diagnostic criteria of Cogan's syndrome, the vestibular symptoms preceded the visual complaints, the reverse temporal sequence being more often reported in the literature. Systemic signs and cardiovascular involvement are frequently seen in Cogan's syndrome, but were notably absent in our patient. Blood samples showed inflammatory signs, whereas both lumbar puncture and cerebral MRI were normal, which is the usual pattern encountered in Cogan's syndrome. Following the rapid initiation of immunosuppressive therapy (Prednisone), the visual symptoms due to the bilateral keratitis resolved in a matter of days, whereas the vestibulocochlear deficit was only partly - but dramatically - reduced. This is in accordance with literature data, showing that a severe and permanent auditory deficit occurs at some time in the majority of patients suffering from Cogan's syndrome. Tapering off Prednisone unfortunately reactivated the audiovestibular and ocular symptoms of the disease in our patient so that a steroid-sparing immunosuppressive drug had to be added (azathioprine, followed by mycophenolate mofetil because the patient developed hepatic intolerance). Only after these therapeutic measures could the disease be stabilised. With this case report, we would like to emphasise the importance of rapidly identifying the clinical picture of Cogan's syndrome, so that immunosuppressive therapy can be started without delay, which may significantly reduce both morbidity and mortality of this disease.

A tennis player with hand claudication.

The case of a professional tennis player presenting exercise-induced hand pain with late appearance of digital blanching is reported. A bilateral hypothenar hammer syndrome and stenosis of the common palmar digital arteries close to the head of the metacarpals where the racket handle exerts its maximal force was observed with arteriography. As the patient decided to stop tennis practice, the condition improved without any medication. Six months after stopping tennis he was symptom free. Three conclusions can be drawn from this case report: 1) arteries of both hands can be injured by intense tennis practice, 2) pain in the dominant hand during tennis practice can be due to arterial insufficiency even in the absence of digital blanching which is a sign of severity, 3) hypothenar hammer syndrome is the main cause but stenosis of the common palmar digital arteries can possibly contribute to the ischemic phenomenon. Early recognition is important to avoid ineffective treatment and permanent symptoms. Therefore, we recommend an arterial examination in tennis players suffering from exercise-induced hand pain even in the absence of digital blanching which can be only a late manifestation.

Transcatheter aortic valve replacement for degenerative bioprosthetic surgical valves: results from the global valve-in-valve registry.

BACKGROUND: Transcatheter aortic valve-in-valve implantation is an emerging therapeutic alternative for patients with a failed surgical bioprosthesis and may obviate the need for reoperation. We evaluated the clinical results of this technique using a large, worldwide registry. METHODS AND RESULTS: The Global Valve-in-Valve Registry included 202 patients with degenerated bioprosthetic valves (aged 77.7±10.4 years; 52.5% men) from 38 cardiac centers. Bioprosthesis mode of failure was stenosis (n=85; 42%), regurgitation (n=68; 34%), or combined stenosis and regurgitation (n=49; 24%). Implanted devices included CoreValve (n=124) and Edwards SAPIEN (n=78). Procedural success was achieved in 93.1% of cases. Adverse procedural outcomes included initial device malposition in 15.3% of cases and ostial coronary obstruction in 3.5%. After the procedure, valve maximum/mean gradients were 28.4±14.1/15.9±8.6 mm Hg, and 95% of patients had ≤+1 degree of aortic regurgitation. At 30-day follow-up, all-cause mortality was 8.4%, and 84.1% of patients were at New York Heart Association functional class I/II. One-year follow-up was obtained in 87 patients, with 85.8% survival of treated patients. CONCLUSIONS: The valve-in-valve procedure is clinically effective in the vast majority of patients with degenerated bioprosthetic valves. Safety and efficacy concerns include device malposition, ostial coronary obstruction, and high gradients after the procedure.

Intrauterine growth restriction is associated with structural alterations in human umbilical cord and decreased nitric oxide-induced relaxation of umbilical vein.

INTRODUCTION: Intrauterine growth restriction (IUGR) affects ∼8% of all pregnancies and is associated with major perinatal mortality and morbidity, and with an increased risk to develop cardiovascular diseases in adulthood. Despite identification of several risk factors, the mechanisms implicated in the development of IUGR remain poorly understood. In case of placental insufficiency, reduced delivery of oxygen and/or nutrients to the fetus could be associated with alterations in the umbilical circulation, contributing further to the impairment of maternal-fetal exchanges. We compared the structural and functional properties of umbilical cords from growth-restricted and appropriate for gestational age (AGA) term newborns, with particular attention to the umbilical vein (UV). METHODS: Human umbilical cords were collected at delivery. Morphological changes were investigated by histomorphometry, and UV's reactivity by pharmacological studies. RESULTS: Growth-restricted newborns displayed significantly lower growth parameters, placental weight and umbilical cord diameter than AGA controls. Total cross-section and smooth muscle areas were significantly smaller in UV of growth-restricted neonates than in controls. Maximal vasoconstriction achieved in isolated UV was lower in growth-restricted boys than in controls, whereas nitric oxide-induced relaxation was significantly reduced in UV of growth-restricted girls compared to controls. CONCLUSION: IUGR is associated with structural alterations of the UV in both genders, and with a decreased nitric oxide-induced relaxation in UV of newborn girls, whereas boys display impaired vasoconstriction. Further investigations will allow to better understand the regulation of umbilical circulation in growth-restricted neonates, which could contribute to devise potential novel therapeutic strategies to prevent or limit the development of IUGR.

Amyloïdose rénale [Renal amyloidosis].

Amyloidosis is defined as the extracellular deposition of proteins that have the capacity to form beta-pleated sheets and become insoluble. More than 17 types of amyloidosis have been described. Systemic light chain amyloid (AL) and AA amyloid (secondary to chronic inflammatory process) are by far the most frequent forms of amyloidosis. In these systemic forms, organs involved are the kidneys, the heart and the gastrointestinal tract in AL amyloidosis. The diagnostic can be established only by tissue biopsy. Treatment of primary amyloidosis (AL) aims at suppressing the responsible clone whereas treatment of secondary amyloidosis relies on controlling the underlying inflammatory process. Prognosis is globally poor and depends on the extend of organs involvement particularly cardiac and renal. The prognosis is even worse in patients requiring dialysis.

Péritonite infectieuse en dialyse péritonéale: une complication trop redoutée [Infectious peritonitis in peritoneal dialysis: an over-emphasized complication].

Peritoneal dialysis is an extrarenal epuration modality which uses physiological properties of peritoneum as a dialysis membrane. Despite the improvement of peritoneal dialysis techniques in the last ten years, peritonitis remains one of the most redoubt complications. Peritonitis may sometimes lead to technical failures, which need catheter removing, but rarely lead to death. Our retrospective study at the dialysis center of CHUV has analyzed factors which can predict this kind of complication. It calculates peritonitis rate and median peritonitis free-survival for different groups of patients. It also describes causatives organisms and their sensitivity to antibiotics.

Aortic valve lesion after coronary angiography.

A 56-year-old patient admitted to hospital for the suspicion of an acute coronary syndrome underwent coronary angiography without detection of significant lesions. Seven days later the echocardiography showed acute severe aortic valve insufficiency. Intraoperatively we found a perforated leaflet probably due to lesion during transcatheter procedure.

Hyponatrémie: une histoire en deux temps... [Hyponatremia: an unusual case report]

Hyponatremia is a frequent finding and asks for a rapid diagnostic evaluation. We report a case of recurrent hyponatremia secondary to an adrenal insufficiency of medicamentous and tuberculous origin. This case illustrates the importance of a rapid etiologic diagnosis of hyponatremia and allows us to review adrenal insufficiency of tuberculous origin. It also stresses the danger of potential drug interactions in case of corticosteroid substitution.

A Prognostic Score to Identify Low-risk Outpatients with Acute Deep Vein Thrombosis in the Lower Limbs.

BACKGROUND: No prior studies have identified which patients with deep vein thrombosis in the lower limbs are at a low risk for adverse events within the first week of therapy. METHODS: We used data from the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) to identify patients at low risk for the composite outcome of pulmonary embolism, major bleeding, or death within the first week. We built a prognostic score and compared it with the decision to treat patients at home. RESULTS: As of December 2013, 15,280 outpatients with deep vein thrombosis had been enrolled. Overall, 5164 patients (34%) were treated at home. Of these, 12 (0.23%) had pulmonary embolism, 8 (0.15%) bled, and 4 (0.08%) died. On multivariable analysis, chronic heart failure, recent immobility, recent bleeding, cancer, renal insufficiency, and abnormal platelet count independently predicted the risk for the composite outcome. Among 11,430 patients (75%) considered to be at low risk, 15 (0.13%) suffered pulmonary embolism, 22 (0.19%) bled, and 8 (0.07%) died. The C-statistic was 0.61 (95% confidence interval [CI], 0.57-0.65) for the decision to treat patients at home and 0.76 (95% CI, 0.72-0.79) for the score (P = .003). Net reclassification improvement was 41% (P < .001). Integrated discrimination improvement was 0.034 for the score and 0.015 for the clinical decision (P < .001). CONCLUSIONS: Using 6 easily available variables, we identified outpatients with deep vein thrombosis at low risk for adverse events within the first week. These data may help to safely treat more patients at home. This score, however, should be validated.

Exposition aux immunosuppresseurs in utero [Exposure in utero to immunosuppressives]

The number of pregnant women receiving immunosuppressive therapy is increasing. Use of immunosuppressants during pregnancy is indicated for anti-rejection therapy in transplantation patients and treatment of autoimmune diseases. Despite the maternal and fetal risks of these pregnancies, the proportion of surviving infants is improving and the possibility that a pregnancy could occur in these women during their childbearing years should be considered. All immunosuppressant drugs and their metabolites cross the placenta, raising questions about the long-term outcome of the children exposed to these agents in utera. There is no increased risk of congenital anomalies. However, there is an elevated incidence of prematurity, intrauterine growth retardation (IUGR) and therefore low birthweight, as well as maternal hypertension and preeclampsia. The most frequent neonatal complications are those associated with prematurity and IUGR, as well as adrenal insufficiency with corticosteroids, immunological disturbances with azathioprine and cyclosporin, and hyperkalemia with tacrolimus. The long-term follow-up of infants exposed to immunosuppressants in utero is still limited and experimental studies raise the question whether there could be an increased incidence at adult age of some pathologies including renal insufficiency, hypertension and diabetes. The follow-up of these infants should be carefully organized and multidisciplinary, taking the perinatal context into account.

Portal vein embolization: what do we know?

Portal vein embolization (PVE) has been developed to increase the size of the future remnant liver (FRL) left in place after major hepatectomy, thus reducing the risk of postoperative liver insufficiency. PVE consist in embolizing preoperatively portal branches of the segments that will be resected. Indication is based on preoperative measurements of the FRL by computed tomography and its ratio with either the theoretical liver volume or by direct measurement of the functional liver volume. After PVE, the volume and function of the FRL increases in 3 to 6 weeks, permitting extensive resections in patients otherwise contraindicated for liver resection. The PVE technique is variable from one center to another; however n-butyl-cyano-acrylate provides an interesting compromise between hypertrophy rate and procedure risk.

Feasibility of non-invasive pressure support ventilation in infants with respiratory failure after extubation: a pilot study.

OBJECTIVE: To evaluate the feasibility and effects of non-invasive pressure support ventilation (NIV) on the breathing pattern in infants developing respiratory failure after extubation. DESIGN: Prospective pilot clinical study; each patient served as their own control. SETTING: A nine-bed paediatric intensive care unit of a tertiary university hospital. PATIENTS: Six patients (median age 5 months, range 0.5-7 months; median weight 4.2 kg, range 3.8-5.1 kg) who developed respiratory failure after extubation. INTERVENTIONS: After a period of spontaneous breathing (SB), children who developed respiratory failure were treated with NIV. MEASUREMENTS AND RESULTS: Measurements included clinical dyspnoea score (DS), blood gases and oesophageal pressure recordings, which were analysed for respiratory rate (RR), oesophageal inspiratory pressure swing (dPes) and oesophageal pressure-time product (PTPes). All data were collected during both periods (SB and NIV). When comparing NIV with SB, DS was reduced by 44% (P < 0.001), RR by 32% (P < 0.001), dPes by 45% (P < 0.01) and PTPes by 57% (P < 0.001). A non-significant trend for decrease in PaCO(2) was observed. CONCLUSION: In these infants, non-invasive pressure support ventilation with turbine flow generator induced a reduction of breathing frequency, dPes and PTPes, indicating reduced load of the inspiratory muscles. NIV can be used with some benefits in infants with respiratory failure after extubation.

Human metabolic individuality in biomedical and pharmaceutical research.

Genome-wide association studies (GWAS) have identified many risk loci for complex diseases, but effect sizes are typically small and information on the underlying biological processes is often lacking. Associations with metabolic traits as functional intermediates can overcome these problems and potentially inform individualized therapy. Here we report a comprehensive analysis of genotype-dependent metabolic phenotypes using a GWAS with non-targeted metabolomics. We identified 37 genetic loci associated with blood metabolite concentrations, of which 25 show effect sizes that are unusually high for GWAS and account for 10-60% differences in metabolite levels per allele copy. Our associations provide new functional insights for many disease-related associations that have been reported in previous studies, including those for cardiovascular and kidney disorders, type 2 diabetes, cancer, gout, venous thromboembolism and Crohn's disease. The study advances our knowledge of the genetic basis of metabolic individuality in humans and generates many new hypotheses for biomedical and pharmaceutical research.

Home versus in-hospital treatment of outpatients with acute deep venous thrombosis of the lower limbs.

BACKGROUND: Some physicians are still concerned about the safety of treatment at home of patients with acute deep venous thrombosis (DVT). METHODS: We used data from the RIETE (Registro Informatizado de la Enfermedad TromboEmbólica) registry to compare the outcomes in consecutive outpatients with acute lower limb DVT according to initial treatment at home or in the hospital. A propensity score-matching analysis was carried out with a logistic regression model. RESULTS: As of December 2012, 13,493 patients had been enrolled. Of these, 4456 (31%) were treated at home. Patients treated at home were more likely to be male and younger and to weigh more; they were less likely than those treated in the hospital to have chronic heart failure, lung disease, renal insufficiency, anemia, recent bleeding, immobilization, or cancer. During the first week of anticoagulation, 27 patients (0.20%) suffered pulmonary embolism (PE), 12 (0.09%) recurrent DVT, and 51 (0.38%) major bleeding; 80 (0.59%) died. When only patients treated at home were considered, 12 (0.27%) had PE, 4 (0.09%) had recurrent DVT, 6 (0.13%) bled, and 4 (0.09%) died (no fatal PE, 3 fatal bleeds). After propensity analysis, patients treated at home had a similar rate of venous thromboembolism recurrences and a lower rate of major bleeding (odds ratio, 0.4; 95% confidence interval, 0.1-1.0) or death (odds ratio, 0.2; 95% confidence interval, 0.1-0.7) within the first week compared with those treated in the hospital. CONCLUSIONS: In outpatients with DVT, home treatment was associated with a better outcome than treatment in the hospital. These data may help safely treat more DVT patients at home.