Spontaneous mediastinal haemorrhage linked with thymic carcinoma and myelodysplasia: a case report

We report an unusual sequence of clinico-pathological manifestations of myelodysplastic syndrome and thymic squamous cell carcinoma. A 77-year-old man with a two-month history of myelodysplastic syndrome was admitted with acute chest pain and shortness of breath. Radiological investigations revealed an anterior mediastinal mass, associated with mediastinal haemorrhage. The mass was excised via a standard median sternotomy and was found to be an infiltrating squamous cell carcinoma, which arose from a multilocular thymic cyst

The role of Solobacterium moorei in oral malodour.

peer reviewedThis study aims to analyze the correlation between Solobacterium moorei (S. moorei), both on the tongue and in saliva, and several oral malodour- and clinical parameters. Data from 193 patients visiting a halitosis clinic were used for analysis. A questionnaire assessed their general health, allergies, medication, smoking habits and oral hygiene. Following halitosis parameters were recorded: organoleptic score (OLS) (0-5), total concentration of volatile sulfur compounds (VSC) (Halimeter), individual concentrations of VSC (Oral Chroma), tongue coating (MTCI, WTCI and mWTCI), salivary parameters (flow rate and pH), oral hygiene, tonsil health and periodontal health. In all subjects, microbiological samples were collected from the tongue coating and from the saliva, and a quantitative polymerase chain reaction was performed to detect S. moorei. A significant correlation could be established between S. moorei, from both tongue and saliva, and several breath parameters (OLS, H2S, CH3SH, (CH3)2S and total VSCs), tongue coating indices and periodontal indices (gingivitis, periodontitis and oral hygiene). This study suggests a strong association between the presence of S. moorei and oral malodour (s54747)

Detected troponin elevation is associated with high early mortality after lung resection for cancer

BACKGROUND: Myocardial infarction can be difficult to diagnose after lung surgery. As recent diagnostic criteria emphasize serum cardiac markers (in particular serum troponin) we set out to evaluate its clinical utility and to establish the long term prognostic impact of detected abnormal postoperative troponin levels after lung resection. METHODS: We studied a historic cohort of patients with primary lung cancer who underwent intended surgical resection. Patients were grouped according to known postoperative troponin status and survival calculated by Kaplan Meier method and compared using log rank. Parametric survival analysis was used to ascertain independent predictors of mortality. RESULTS: From 2001 to 2004, a total of 207 patients underwent lung resection for primary lung cancer of which 14 (7%) were identified with elevated serum troponin levels within 30 days of surgery, with 9 (64%) having classical features of myocardial infarction. The median time to follow up (interquartile range) was 22 (1 to 52) months, and the one and five year survival probabilities (95% CI) for patients without and with postoperative troponin elevation were 92% (85 to 96) versus 60% (31 to 80) and 61% (51 to 71) versus 18% (3 to 43) respectively (p < 0.001). T stage and postoperative troponin elevation remained independent predictors of mortality in the final multivariable model. The acceleration factor for death of elevated serum troponin after adjusting for tumour stage was 9.19 (95% CI 3.75 to 22.54). CONCLUSION: Patients with detected serum troponin elevation are at high risk of early mortality with or without symptoms of myocardial infarction after lung resection

phase 2 study evaluating intermittent and continuous linsitinib and weekly paclitaxel in patients with recurrent platinum resistant ovarian epithelial cancer

Abstract Background Linsitinib, an oral, dual inhibitor of insulin-like growth factor-1 receptor and insulin receptor, in combination with weekly paclitaxel, may improve clinical outcomes compared with paclitaxel alone in patients with refractory or platinum-resistant ovarian cancer. Patients and methods This open-label phase 1/2 clinical trial (NCT00889382) randomized patients with refractory or platinum-resistant ovarian cancer (1:1:1) to receive either oral intermittent linsitinib (600mg once daily on Days 1–3 per week) combined with paclitaxel (80mg/m 2 on Days 1, 8, and 15; Arm A) or continuous linsitinib (150mg twice daily) in combination with paclitaxel (Arm B), or paclitaxel alone (Arm C). Primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), overall response rate (ORR), disease control rate (DCR), and safety/tolerability. Results A total of 152 women were randomized to treatment (n=51 Arm A; n=51 Arm B, n=50 Arm C). In combination with paclitaxel, neither intermittent linsitinib (median PFS 2.8months; 95% confidence interval [CI]:2.5–4.4) nor continuous linsitinib (median PFS 4.2months; 95% CI:2.8–5.1) improved PFS over weekly paclitaxel alone (median PFS 5.6months; 95% CI:3.2–6.9). No improvement in ORR, DCR, or OS in either linsitinib dosing schedule was observed compared with paclitaxel alone. Adverse event (AE) rates, including all-grade and grade 3/4 treatment-related AEs, and treatment-related AEs leading to discontinuation, were higher among patients receiving intermittent linsitinib compared with the other treatment arms. Conclusion Addition of intermittent or continuous linsitinib with paclitaxel did not improve outcomes in patients with platinum-resistant/refractory ovarian cancer compared with paclitaxel alone

A randomized phase II study of SM-88 plus methoxsalen, phenytoin, and sirolimus in patients with metastatic pancreatic cancer treated in the second line and beyond

BACKGROUND: This trial explores SM-88 used with methoxsalen, phenytoin, and sirolimus (MPS) in pretreated metastatic pancreatic ductal adenocarcinoma (mPDAC) METHODS: Forty-nine patients were randomized to daily 460 or 920 mg oral SM-88 with MPS (SM-88 Regimen). The primary endpoint was objective response rate (RECIST 1.1). RESULTS: Thirty-seven patients completed ≥ one cycle of SM-88 Regimen (response evaluable population). Disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) did not differ significantly between dose levels. Stable disease was achieved in 9/37 patients (DCR, 24.3%); there were no complete or partial responses. Quality-of-life (QOL) was maintained and trended in favor of 920 mg. SM-88 Regimen was well tolerated; a single patient (1/49) had related grade 3 and 4 adverse events, which later resolved. In the intention-to-treat population of 49 patients, the median overall survival (mOS) was 3.4 months (95% CI: 2.7-4.9 months). Those treated in the second line had an mOS of 8.1 months and a median PFS of 3.8 months. Survival was higher for patients with stable versus progressive disease (any line; mOS: 10.6 months vs. 3.9 months; p = 0.01). CONCLUSIONS: SM-88 Regimen has a favorable safety profile with encouraging QOL effects, disease control, and survival trends. This regimen should be explored in the second-line treatment of patients with mPDAC. CLINICALTRIALS: gov Identifier: NCT03512756

A first in man, dose-finding study of the mTORC1/mTORC2 inhibitor OSI-027 in patients with advanced solid malignancies.

Background The kinase activity of mTOR involves 2 multiprotein complexes, (mTORC1-mTORC2). Targeting mTORC1 with rapalogues induces compensatory feedback loops resulting in AKT/ERK activation, which may be abrogated by mTORC2 inhibition. A first-in-human trial evaluating tolerability, pharmacokinetics and pharmacodynamics of the dual TORC1/TORC2 inhibitor OSI-027 was conducted.Methods Dose escalation was pursued for three schedules of administration (three consecutive days per week (S1), once a week (S2) and daily dosing (S3)), until dose-limiting toxicities (DLT) were identified. Expansion cohorts with paired tumour biopsies were initiated based on tolerability and pharmacodynamics.Results One hundred and twenty eight patients with advanced cancer were enrolled. DLT consisted predominantly of fatigue, renal function disturbances and cardiac events. OSI-027 exposure was dose proportional, with Tmax within 4 h and a half-life of ∼14 h. Expansion cohorts were initiated for S1 and S2, as MTD for S3 was overall considered suboptimal. Target modulation in peripheral blood mononuclear cells were observed from 30 mg, but in tumour biopsies 120 mg QD were needed, which was a non-tolerable dose due to renal toxicity. No RECIST responses were recorded, with stable disease >6 months in six (5%) patients.Conclusions OSI-027 inhibits mTORC1/2 in patients with advanced tumour s in a dose-dependent manner but doses above the tolerable levels in S1 and S3 are required for a sustained biological effect in tumour biopsies

Spontaneous remodeling of HDL particles at acidic pH enhances their capacity to induce cholesterol efflux from human macrophage foam cells

Peer reviewe

Clinical Significance of Serum Biomarkers in Pediatric Solid Mediastinal and Abdominal Tumors

Childhood cancer is the leading cause of death by disease among U.S. children between infancy and age 15. Despite successes in treating solid tumors such as Wilms tumor, disappointments in the outcomes of high-risk solid tumors like neuroblastoma have precipitated efforts towards the early and accurate detection of these malignancies. This review summarizes available solid tumor serum biomarkers with a special focus on mediastinal and abdominal cancers in children

Tongue coating: related factors

AIM: A clear relationship between tongue coating and oral malodour has been observed in many clinical trials. Why or when this coating is formed remains an open question. The aim of this study was to analyse possible factors related to the presence of tongue coating in a population complaining from oral malodour. MATERIALS AND METHODS: Patients were recruited from a halitosis clinic (UZ Leuven). Medical history, dietary and oral hygiene habits were retrieved via a questionnaire. Data were recorded on organoleptic score and level of sulphur compounds in breath, anatomical features of the tongue dorsum, amount of tongue coating (according to three indices: Miyazaki, Winkel and modified Winkel), tongue coating wet weight and salivary flow. The correlation between the presence of tongue coating and a series of parameters was analysed. RESULTS: The level of oral hygiene was the strongest determinant factor for the presence of tongue coating. Smoking, presence of a denture, periodontal status and dietary habits also correlated although less obvious. CONCLUSION: The presence of tongue coating appears to be related to several factors of which oral hygiene is the strongest.status: publishe