Author’s reply to ‘Letter to the Editor’: Use of Almelo Hip Fracture Score to predict early mortality following hip fracture surgery

Publication date: Available online 4 May 2017
Source:Injury
Author(s): W.S. Nijmeijer, E.C. Folbert, J.H. Hegeman




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Insertion-related pain with intramedullary nailing

Publication date: Available online 5 May 2017
Source:Injury
Author(s): Yohan Jang, Laurence B. Kempton, Todd O. Mckinley, Anthony T. Sorkin
The use of intramedullary nails for the treatment of long bone fractures has become increasingly frequent over the last decade with gradually expanding indications and technological advances. Improved biomechanics relative to plates and less direct fracture exposure are some of the potential benefits of intramedullary nails. However, persistent insertion-related pain is common and may limit satisfactory long term outcomes. The etiologies of this phenomenon remain unclear. Proposed theories for which there is a growing body of supporting evidence include hardware prominence, suboptimal nail entry points leading to soft tissue irritation and structural compromise, local heterotrophic ossification, implant instability with persistent fracture micromotion, and poorly defined insertional strain. Many factors that lead to insertion-related pain are iatrogenic, and careful attention to detail and refined surgical techniques will optimize outcomes.



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Integration of radiotherapy and chemotherapy for abdominal lymph node recurrence in gastric cancer

Abstract

Purpose

Abdominal lymph node (ALN) recurrence in gastric cancer (GC) is rare and usually unresectable. We investigated the effects of integration of radiotherapy (RT) and chemotherapy against ALN recurrence in GC.

Methods

We retrospectively categorized GC patients with ALN recurrence treated between 2005 and 2013 into two groups: those treated with integration of RT and chemotherapy (RCT) and those who received systemic chemotherapy only (CT). The median follow-up period after ALN recurrence for all patients was 20 months.

Results

Of 53 patients, 31 and 22 were in the RCT and CT groups, respectively. Isolated distant failure (DF; 35.5%) without local progression (LP) was the dominant pattern of failure (POF) in the RCT group (median DF-free period, 26 months). LP followed by DF (31.8%) was the dominant POF in the CT group; LP (median LP-free period, 8 months) occurred 10 months earlier than DF (median DF-free period, 18 months). RCT patients had significantly longer median progression-free survival (PFS) compared to CT patients (25 vs. 8 months; P = 0.021). On multivariate analysis, treatment (CT vs. RCT) was an independent prognostic factor for PFS (hazard ratio 2.085; 95% confidence interval 1.073–4.050; P = 0.013).

Conclusions

Integration of RT and chemotherapy achieved long-term local control and prolonged PFS in GC patients with ALN recurrence. Local RT is feasible for treating isolated ALN recurrences.

http://ift.tt/2qAxfz6

Calif. community paramedicine project results in continued success

UCSF Healthforce Center MODESTO, Calif. — A new independent study of California's Community Paramedicine pilot projects shows encouraging results, demonstrating how specially trained paramedics can safely help improve patient care, reduce unnecessary emergency department transports, and lower health care costs. The study by the University of California, San Francisco (UCSF) Healthforce Center ...

http://ift.tt/2pIQtla

Epigenetic down regulation of G protein-coupled estrogen receptor (GPER) functions as a tumor suppressor in colorectal cancer

Abstract

Background

Estrogenic signals are suggested to have protection roles in the development of colorectal cancer (CRC). The G protein-coupled estrogen receptor (GPER) has been reported to mediate non-genomic effects of estrogen in hormone related cancers except CRC. Its expression and functions in CRC were investigated.

Methods

The expression of GPER and its associations with clinicopathological features were examined. The mechanisms were further investigated using cells, mouse xenograft models, and clinical human samples.

Results

GPER was significantly (p < 0.01) down regulated in CRC tissues compared with their matched adjacent normal tissues in our two cohorts and three independent investigations from Oncomine database. Patients whose tumors expressing less (n = 36) GPER showed significant (p < 0.01) poorer survival rate as compared with those with greater levels of GPER (n = 54). Promoter methylation and histone H3 deacetylation were involved in the down regulation of GPER in CRC cell lines and clinical tissues. Activation of GPER by its specific agonist G-1 inhibited proliferation, induced cell cycle arrest, mitochondrial-related apoptosis and endoplasmic reticulum (ER) stress of CRC cells. The upregulation of reactive oxygen species (ROS) induced sustained ERK1/2 activation participated in G-1 induced cell growth arrest. Further, G-1 can inhibit the phosphorylation, nuclear localization, and transcriptional activities of NF-κB via both canonical IKKα/ IκBα pathways and phosphorylation of GSK-3β. Xenograft model based on HCT-116 cells confirmed that G-1 can suppress the in vivo progression of CRC.

Conclusions

Epigenetic down regulation of GPER acts as a tumor suppressor in colorectal cancer and its specific activation might be a potential approach for CRC treatment.

http://ift.tt/2q7tUrt

A phase I study of cilengitide and paclitaxel in patients with advanced solid tumors

Abstract

Purpose

Cilengitide is a potent and selective inhibitor of the integrins αvβ3 and αvβ5. The primary objective of this phase I clinical trial was to establish the maximum tolerated dose and determine safety/tolerability of cilengitide in combination with paclitaxel in patients with advanced solid tumors. Secondary objectives included the evaluation of the preliminary clinical outcomes.

Patients and methods

Patients with advanced solid tumors experiencing disease progression on standard treatment were assigned to two different dose levels of cilengitide (2000 mg intravenously once or twice weekly) in combination with fixed-dose, weekly paclitaxel (90 mg/m² intravenously).

Results

Twelve evaluable patients were treated per protocol. A single dose limiting toxicity (DLT) of grade 4 neutropenia was observed at the starting dose level of once weekly cilengitide. There were no grade ≥3 adverse events that occurred with >10% frequency. One patient achieved a partial response to therapy. Five patients experienced stable disease as best response, 3 of which discontinued study participation due to progressive, peripheral neuropathy.

Conclusions

Cilengitide in combination with paclitaxel was well tolerated. Antitumor activity was observed. The recommended phase II dose is twice weekly cilengitide (2000 mg) with weekly paclitaxel (90 mg/m²). Further studies evaluating drugs that target this pathway are warranted.

http://ift.tt/2pIIlRu

Phase Separation and Single-Chain Compactness of Charged Disordered Proteins Are Strongly Correlated

Liquid-liquid phase separation of intrinsically disordered proteins (IDPs) is a major undergirding factor in the regulated formation of membraneless organelles in the cell. The phase behavior of an IDP is sensitive to its amino acid sequence. Here we apply a recent random-phase-approximation polymer theory to investigate how the tendency for multiple chains of a protein to phase-separate, as characterized by the critical temperature T∗cr, is related to the protein's single-chain average radius of gyration 〈Rg〉.

http://ift.tt/2p51UVt