Ovarian Sertoli–Leydig cell tumours: How typical is their typical presentation?

Ovarian Sertoli–Leydig cell tumours (OSLCT) are rare and typically present with androgenic manifestations in women of the 2nd–3rd decade. Out of 228 diagnoses of ovarian sex cord-stromal tumours recorded at an academic institution during a 14-year period, eight women were surgically treated for OSLCT. Patient mean age was 54.8 years (range 19–81), five women being in the postmenopausal stage (62.5%). Only one woman presented with androgenic manifestations (12.5%), four with abnormal/postmenopausal uterine bleeding (50%), and three with abdominal pain (37.5%). Fertility sparing or radical surgery was performed depending on patient age and stage of disease. The only patient with an advanced disease (FIGO stage IV) was referred to palliative care postoperatively. The other seven were at FIGO stage I. Five of them were free from disease at a mean follow-up of 67 months, while the remaining two were lost at follow-up. The youngest woman of the series, treated with fertility-preserving unilateral salpingo-oophorectomy at the age of 19, had two spontaneous pregnancies and deliveries of healthy babies during a 10-year follow-up period. In conclusion, our single institution 14-year experience demonstrates that the diagnosis of OSLCT is particularly challenging since many patients are older than expected and lack androgenic manifestations.Impact statement • What is already known on this subjectOvarian Sertoli–Leydig cell tumours (OSLCT) are rare and are thought to typically present with androgenic manifestations in women of the 2nd–3rd decade. • What the results of this study addOur single institution 14-year experience shows that a high proportion of women with ovarian Sertoli–Leydig cell tumours may not present with androgenic manifestations, and many of them also are in the postmenopausal stage. Most patients have a good prognosis and fertility-preserving surgery in younger women can lead to spontaneous pregnancies and deliveries of healthy children after treatment. • What are the implications of these findings for clinical practice and/or further researchThe diagnosis of OSLCT is particularly challenging and therefore not reached before surgery in most of the cases. However, while hysterectomy with bilateral salpingo-oophorectomy and surgical staging are recommended for women with higher stage or no fertility wish, fertility-sparing surgery should be considered in younger women with early disease. Therefore, further research should focus on non-invasive diagnosis possibly by means of laboratory or imaging techniques

Assessment of plasma chitotriosidase activity, CCL18/PARC concentration and NP-C suspicion index in the diagnosis of Niemann-Pick disease type C : A prospective observational study

Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. The diagnosis of NP-C remains challenging due to the non-specific, heterogeneous nature of signs/symptoms. This study assessed the utility of plasma chitotriosidase (ChT) and Chemokine (C-C motif) ligand 18 (CCL18)/pulmonary and activation-regulated chemokine (PARC) in conjunction with the NP-C suspicion index (NP-C SI) for guiding confirmatory laboratory testing in patients with suspected NP-C. In a prospective observational cohort study, incorporating a retrospective determination of NP-C SI scores, two different diagnostic approaches were applied in two separate groups of unrelated patients from 51 Spanish medical centers (n = 118 in both groups). From Jan 2010 to Apr 2012 (Period 1), patients with ≥2 clinical signs/symptoms of NP-C were considered 'suspected NP-C' cases, and NPC1/NPC2 sequencing, plasma chitotriosidase (ChT), CCL18/PARC and sphingomyelinase levels were assessed. Based on findings in Period 1, plasma ChT and CCL18/PARC, and NP-C SI prediction scores were determined in a second group of patients between May 2012 and Apr 2014 (Period 2), and NPC1 and NPC2 were sequenced only in those with elevated ChT and/or elevated CCL18/PARC and/or NP-C SI ≥70. Filipin staining and 7-ketocholesterol (7-KC) measurements were performed in all patients with NP-C gene mutations, where possible. In total across Periods 1 and 2, 10/236 (4%) patients had a confirmed diagnosis o NP-C based on gene sequencing (5/118 [4.2%] in each Period): all of these patients had two causal NPC1 mutations. Single mutant NPC1 alleles were detected in 8/236 (3%) patients, overall. Positive filipin staining results comprised three classical and five variant biochemical phenotypes. No NPC2 mutations were detected. All patients with NPC1 mutations had high ChT activity, high CCL18/PARC concentrations and/or NP-C SI scores ≥70. Plasma 7-KC was higher than control cut-off values in all patients with two NPC1 mutations, and in the majority of patients with single mutations. Family studies identified three further NP-C patients. This approach may be very useful for laboratories that do not have mass spectrometry facilities and therefore, they cannot use other NP-C biomarkers for diagnosis

Evolution over Time of Ventilatory Management and Outcome of Patients with Neurologic Disease∗

OBJECTIVES: To describe the changes in ventilator management over time in patients with neurologic disease at ICU admission and to estimate factors associated with 28-day hospital mortality. DESIGN: Secondary analysis of three prospective, observational, multicenter studies. SETTING: Cohort studies conducted in 2004, 2010, and 2016. PATIENTS: Adult patients who received mechanical ventilation for more than 12 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 20,929 patients enrolled, we included 4,152 (20%) mechanically ventilated patients due to different neurologic diseases. Hemorrhagic stroke and brain trauma were the most common pathologies associated with the need for mechanical ventilation. Although volume-cycled ventilation remained the preferred ventilation mode, there was a significant (p < 0.001) increment in the use of pressure support ventilation. The proportion of patients receiving a protective lung ventilation strategy was increased over time: 47% in 2004, 63% in 2010, and 65% in 2016 (p < 0.001), as well as the duration of protective ventilation strategies: 406 days per 1,000 mechanical ventilation days in 2004, 523 days per 1,000 mechanical ventilation days in 2010, and 585 days per 1,000 mechanical ventilation days in 2016 (p < 0.001). There were no differences in the length of stay in the ICU, mortality in the ICU, and mortality in hospital from 2004 to 2016. Independent risk factors for 28-day mortality were age greater than 75 years, Simplified Acute Physiology Score II greater than 50, the occurrence of organ dysfunction within first 48 hours after brain injury, and specific neurologic diseases such as hemorrhagic stroke, ischemic stroke, and brain trauma. CONCLUSIONS: More lung-protective ventilatory strategies have been implemented over years in neurologic patients with no effect on pulmonary complications or on survival. We found several prognostic factors on mortality such as advanced age, the severity of the disease, organ dysfunctions, and the etiology of neurologic disease