The expression of Mirc1/Mir17–92 cluster in sputum samples correlates with pulmonary exacerbations in cystic fibrosis patients

Introduction

Cystic fibrosis (CF) is a multi-organ disorder characterized by chronic sino-pulmonary infections and inflammation. Many patients with CF suffer from repeated pulmonary exacerbations that are predictors of worsened long-term morbidity and mortality. There are no reliable markers that associate with the onset or progression of an exacerbation or pulmonary deterioration. Previously, we found that the Mirc1/Mir17–92a cluster which is comprised of 6 microRNAs (Mirs) is highly expressed in CF mice and negatively regulates autophagy which in turn improves CF transmembrane conductance regulator (CFTR) function. Therefore, here we sought to examine the expression of individual Mirs within the Mirc1/Mir17–92 cluster in human cells and biological fluids and determine their role as biomarkers of pulmonary exacerbations and response to treatment.

Loss of SMARCE1 expression is a specific diagnostic marker of clear cell meningioma: a comprehensive immunophenotypical and molecular analysis

Clear cell meningioma (CCM) is a rare grade II histopathological subtype that usually occurs in young patients and displays high recurrence rate. Germline SMARCE1 mutations have been described in hereditary forms of this disease and more recently in small syndromic and sporadic CCM series. The diagnostic value of SMARCE1 in distinguishing between CCM and other meningioma variants has not been yet established. The aim of our study was to investigate the status of SMARCE1 in a series of CCMs and its morphological mimickers. We compared the performance of an anti‐SMARCE1 antibody and the molecular analysis of the SMARCE1 gene in a retrospective multicenter series of CCMs. All CCMs lossed SMARCE1 immunoexpression. Bi‐allelic inactivating events were found by NGS‐based sequencing in all of these cases, except for one, which was incompletely explored, but had a wild‐type sequence. We then validated the anti‐SMARCE1 antibody specificity by analyzing additional 305 pediatric and adult meningiomas of various subtypes and 15 non‐meningioma clear cell tumors by SMARCE1 immunohistochemistry. A nuclear immunostaining was preserved in all other meningioma variants, as well as non‐meningioma clear cell tumors. In conclusion, our series showed, for the first time, that SMARCE1 immunostaining is a highly sensitive biomarker for CCM, useful as a routine diagnostic biomarker.     

Fistules urétéro-vaginales : A propos de 15 cas

Objectives

To evaluate the epidemiological, etiopathogenic, diagnostic and prognostic aspects, as well as the treatment of uretero-vaginal fistulas based on a review of 15 cases.

Patients and Methods

Between September 1989 and January 2006 we treated and followed 15 patients admitted for uretero-vaginal fistulas. We analyzed the circumstances of diagnosis, the etiology of the fistulas, the treatment chosen and the results.

Results

The patients’ mean age was 43.8 years. In most of the cases (93%) the fistulas were caused during gyneco-obstetric surgery. Diagnosis was based on physical examination, a continence test and gynecological speculum examination. Ureteral injury and upper urinary tract lesions were assessed by intravenous urography. Treatment consisted of insertion of a double-J catheter in 2, ureterovesical reimplantation in 6, resection with end-to-end anastomosis in 6 (one of them after failure of double-J insertion) and nephrectomy in one case. Treatment was successful in 83% of the patients treated with resection and end-to-end anastomosis and in 67% of the patients treated with ureterovesical reimplantation. One patient who was not operated due to a neoplastic fistula was lost to follow-up.

Conclusion

Uretero-vaginal fistulas are rare and may occur in the setting of gynecologic surgery. Several treatment modalities have been described for their repair. In our series, resection with end-to-end anastomosis after pre-operative ureteroscopy has shown the most satisfactory results.     

Traitement conservateur dans les formes localisées des tumeurs de la voie excrétrice supérieure: Une nouvelle observation et revue de la littérature

Radical nephroureterectomy with a bladder cuff remains the treatment of choice of transitional cell carcinoma of the upper urinary tract. Conservative treatment mainly presents an alternative for patients at risk of developing terminal renal insufficiency after nephroureterectomy and may be indicated for localized tumors of low grade and stage requiring regular, relatively non-invasive monitoring. We report the case of a patient who presented with a localized transitional cell carcinoma of the left pelvic ureter, which was managed by conservative treatment yielding successful results after a follow-up of 10 years. Based on this observation and a review of the literature we discuss the various aspects of conservative treatment of localized transitional cell carcinoma of the ureter.     

Clinical picture of Pneumocystis jiroveci pneumonia in cancer patients

BACKGROUND: Pneumocystis pneumonia (PCP) is common in patients with HIV infection but may also occur in patients with other causes of immunodeficiency, including hematologic and solid malignancies. METHODS: To better describe the clinical picture of PCP as to maintain a high level of suspicion in adequate cases, we studied 56 cancer patients with PCP and compared them to 56 cancer patients with bacterial pneumonia. RESULTS: Among 56 PCP patients, 44 patients (78.6%) had hematologic malignancies (18 recipients of bone marrow transplantation) and 12 patients had solid tumors. The time since diagnosis was 24 months (range, 4 to 49 months). All patients with solid tumors and 20 patients (45.4%) with hematologic malignancies were receiving steroids. Only six patients were receiving PCP prophylaxis. The main symptoms were fever (85.7%), dyspnea (78.6%), and cough (57.1%). Time from symptom onset was 7 days (range, 3 to 14 days). PCP presented as severe pneumonia (Pao(2), 58 mm Hg [range, 50 to 70 mm Hg]) with bilateral interstitial infiltrates (80.4%) and bilateral ground-glass attenuation (89.3%) by CT. Of the 24 ICU patients (42.9%), 16 patients (19.6%) required mechanical ventilation. Eleven patients (19.6%) died. Compared to 56 patients with bacterial pneumonia, PCP patients were more likely to have non-Hodgkin lymphoma and be receiving long-term steroids; they had longer times since diagnosis, longer symptom duration, higher frequencies of fever and of diffuse lung disease (diffuse crackles, bilateral infiltrates, and hypoxemia), higher frequency of ground-glass opacities, and lower frequency of pleural involvement. CONCLUSIONS: PCP presents as subacute, febrile, hypoxemic, and diffuse pulmonary involvement in patients with solid tumors or hematologic malignancies receiving long-term steroids.     

Discrepant effects of inducible nitric oxide synthase modulation on systemic and splanchnic endothelial nitric oxide synthase activity and expression in cirrhotic rats

BACKGROUND: Arterial vasodilatation, which is a major factor in the pathogenesis of the hyperkinetic circulatory state and portal hypertension in cirrhosis, is due to arterial nitric oxide (NO) overproduction secondary to endothelial NO synthase (eNOS) and inducible NOS (iNOS) upregulation. However, in cirrhosis, the respective roles of eNOS and iNOS isoforms in NO overproduction are still unknown and the effect of iNOS modulation on eNOS activity and expression has not been evaluated in the systemic or splanchnic vessels. The aim of this study was to evaluate the effects of modulating aortic and superior mesenteric arteries (SMA) iNOS on arterial eNOS activity and expression in rats with cirrhosis. METHODS: eNOS and iNOS protein expression and eNOS activity (assessed by its phosphorylation at serine 1177) were measured in the aortas and SMA in untreated and treated cirrhotic rats with lipopolysaccharide (LPS), N-iminoethyl-L-lysine (L-NIL), a selective iNOS inhibitor, and LPS plus L-NIL. RESULTS: LPS administration significantly increased eNOS and iNOS protein expression and eNOS activity in the aortas of both sham-operated and cirrhotic rats. However, in SMA, LPS administration induced a decrease in eNOS protein expression and activity and an increase in iNOS protein expression. CONCLUSION: The results of this study may explain the worsening of the hyperdynamic state in cirrhosis during septic shock by direct LPS-induced eNOS activation in large systemic vessels, and its inhibition in concomitant small splanchnic vasculature by iNOS synthesized NO.