High expression of estrogen receptor alpha and aromatase in glial tumor cells is associated with gender-independent survival benefits in glioblastoma patients

Journal of Neuro-Oncology - Glioblastoma multiforme (GBM) is a highly malignant glial tumor, affecting men more often than women. The reason for this gender-specific predominance remains unclear,...     

Lithium decreases secretion of Abeta1-42 and C-truncated species Abeta1-37/38/39/40 in chicken telencephalic cultures but specifically increases intracellular Abeta1-38

We studied endogenous amyloid precursor protein (APP) processing and amyloid beta (Abeta) peptide formation in primary chicken telencephalic neurons, because their Abeta peptide sequence is identical to humans. As detected by quantitative Abeta-SDS-PAGE/immunoblot, Abeta peptides 1-40/42 and three additional C-truncated species, namely Abeta1-37/38/39 were regularly released into the supernatant. The highly conserved Abeta quintet strongly resembles the pattern of Abeta peptides found in human cerebrospinal fluid. Furthermore, the C-terminally shorter Abeta peptides 1-33/34 could be readily detected. Recent evidence indicates that lithium specifically inhibits secretion of the amyloidogenic Abeta1-42 peptide in cultured permanent cells transfected with human APP. We therefore investigated the effect of lithium on Abeta peptide secretion as well as intracellular Abeta peptides in our untransfected primary cell culture system. Our data shows that lithium leads to a dose-dependent reduction of Abeta1-37/38/39/40/42 secretion. Surprisingly, intracellular analysis revealed that lithium specifically increases a band comigrating with synthetic Abeta1-38 while Abeta1-40 and Abeta1-42 remained almost unaffected. These results demonstrate for the first time that lithium treatment decreases Abeta peptide secretion in primary chicken neuronal cells but specifically elevates intracellular Abeta1-38. Therefore, we conclude that there are two independent mechanisms of lithium in intra- and extracellular Abeta peptide production.     

Comparison of wound healing and patient comfort in partial‐thickness burn wounds treated with SUPRATHEL and epictehydro wound dressings

Among the available dressings for partial‐thickness burn wound treatment, SUPRATHEL has shown good usability and effectiveness for wound healing and patient comfort and has been used in many burn centres in the last decade. Recently, bacterial nanocellulose (BNC) has become popular for the treatment of wounds, and many studies have demonstrated its efficacy. epicite^hydro, consisting of BNC and 95% water, is a promising product and has recently been introduced in numerous burn centres. To date, no studies including direct comparisons to existing products like SUPRATHEL have been conducted. Therefore, we aimed to compare epicite^hydro to SUPRATHEL in the treatment of partial‐thickness burns. Twenty patients with partial‐thickness burns affecting more than 0.5% of their total body surface area (TBSA) were enrolled in this prospective, unicentric, open, comparative, intra‐individual clinical study. After debridement, the wounds were divided into two areas: one was treated with SUPRATHEL and the other with epicite^hydro. Wound healing, infection, bleeding, exudation, dressing changes, and pain were documented. The quality of the scar tissue was assessed subjectively using the Patient and Observer Scar Scale. Wound healing in patients with a mean TBSA of 9.2% took 15 to 16 days for both treatments without dressing changes. All wounds showed minimal exudation, and patients reported decreased pain with the only significant difference between the two dressings on day 1. No infection or bleeding occurred in any of the wounds. Regarding scar evaluation, SUPRATHEL and epicite^hydro did not differ significantly. Both wound dressings were easy to use, were highly flexible, created a safe healing environment, had similar effects on pain reduction, and showed good cosmetic and functional results without necessary dressing changes. Therefore, epicite^hydro can be used as an alternative to SUPRATHEL for the treatment of partial‐thickness burn wounds.     

Inadequate Timing Limits the Benefit of Antenatal Corticosteroids on Neonatal Outcome: Retrospective Analysis of a High-Risk Cohort of Preterm Infants in a Tertiary Center in Germany

Introduction A common problem in the treatment of threatened preterm birth is the timing and the unrestricted use of antenatal corticosteroids (ACS). This study was performed to evaluate the independent effects of the distinct timing of antenatal corticosteroids on neonatal outcome parameters in a cohort of very low (VLBW; 1000 – 1500 g) and extreme low birth weight infants (ELBW; < 1000 g). We hypothesize that a prolonged ACS-to-delivery interval leads to an increase in respiratory complications. Materials and Methods Main data source was the prospectively collected single center data for the German nosocomial infection surveillance system (KISS) between 2015 and 2018. Multivariate regression analysis was performed to determine independent effects of the ACS-to-delivery interval on the need for ventilation, surfactant or the occurrence of bronchopulmonary dysplasia, neonatal sepsis or necrotizing enterocolitis. Subgroup analysis was performed for ELBW and VLBW neonates. Results A total of 239 neonates were included. We demonstrate a significantly increased risk of respiratory distress characterized by the need for ventilation (OR 1.045; CI 1.011 – 1.080) and surfactant administration (OR 1.050, CI 1.018 – 1.083) depending on the ACS-to-delivery interval irrespective of other confounders. Every additional day between ACS and delivery increased the risk for ventilation by 4.5% and for surfactant administration by 5%. Subgroup analysis revealed significant differences of respiratory complications in VLBW infants. Conclusions Our data strongly support the deliberate use and timing of antenatal corticosteroids in pregnancies with threatened preterm birth versus a liberal strategy. When given more than 7 days before birth, each day between application and delivery increases is relevant concerning major effects on the infant. Especially VLBW preterm neonates benefit from optimal timing. Key words: antenatal corticosteroids, preterm birth, VLWB, perinatal outcome, respiratory distress syndrome     

A Multi-institutional Analysis of Duodenal Neuroendocrine Tumors: Tumor Biology Rather than Extent of Resection Dictates Prognosis

Introduction

Duodenal neuroendocrine tumors (NETs) are rare neoplasms with poorly defined management. We sought to evaluate the outcomes of patients undergoing resection of duodenal NETs.

Methods

Using a multi-institutional database, 146 patients who underwent resection for duodenal NETs between 1993 and 2015 were identified. Data on clinicopathologic characteristics and outcomes were collected and analyzed.

Results

Local surgical resection (LR) was performed in 57 (39.0 %) patients, while 50 (34.3 %) patients underwent pancreaticoduodenectomy (PD) and 39 (26.7 %) patients an endoscopic resection (ER). Factors associated with worse RFS included advanced tumor grade and metastasis at diagnosis (both P?<?0.05) but not procedure type (P?>?0.05). Among patients who had at least one lymph node examined (n?=?85), 50 (58.8 %) had a metastatic lymph node; lymph node metastasis (P?=?0.04) and advanced tumor grade (P?=?0.04) were more common among patients with tumors >1.5 cm. Median length-of-stay was longer for PD versus LR (P?<?0.001). PD patients were at increased risk for severe postoperative complications (P?=?0.01).

Conclusion

Recurrence of duodenal NETs was dependent on tumor biology rather than procedure type. PD was associated with a longer hospital stay and higher risk of perioperative complications. For patients with tumors ≤1.5 cm, LR or ER may be appropriate with PD reserved for larger lesions and those not amenable to a more local approach.

     

Pancreatic Neuroendocrine Tumors: Radiographic Calcifications Correlate with Grade and Metastasis

Background

Studies to identify preoperative prognostic variables for pancreatic neuroendocrine tumor (PNET) have been inconclusive. Specifically, the prevalence and prognostic significance of radiographic calcifications in these tumors remains unclear.

Methods

From 1998 to 2009, a total of 110 patients with well-differentiated PNET underwent surgical resection at our institution. Synchronous liver metastases present in 31 patients (28%) were addressed surgically with curative intent. Patients with high-grade PNET were excluded. The presence of calcifications in the primary tumor on preoperative computed tomography was recorded and correlated with clinicopathologic variables and overall survival.

Results

Calcifications were present in 16% of patients and were more common in gastrinomas and glucagonomas (50%), but never encountered in insulinomas. Calcified tumors were larger (median size 4.5 vs. 2.3?cm, P?=?0.04) and more commonly associated with lymph node metastasis (75 vs. 35%, P?=?0.01), synchronous liver metastasis (62 vs. 21%, P?P?P?=?0.01) and size (P?P?=?0.04), but not in the presence of radiographic calcifications.

Conclusions

Calcifications on preoperative computed tomography correlate with intermediate grade and lymph node metastasis in well-differentiated PNET. This information is available preoperatively and supports the routine dissection of regional lymph nodes through formal pancreatectomy rather than enucleation in calcified PNET.