Implanted adipose progenitor cells as physicochemical regulators of breast cancer

Multipotent adipose-derived stem cells (ASCs) are increasingly used for regenerative purposes such as soft tissue reconstruction following mastectomy; however, the ability of tumors to commandeer ASC functions to advance tumor progression is not well understood. Through the integration of physical sciences and oncology approaches we investigated the capability of tumor-derived chemical and mechanical cues to enhance ASC-mediated contributions to tumor stroma formation. Our results indicate that soluble factors from breast cancer cells inhibit adipogenic differentiation while increasing proliferation, proangiogenic factor secretion, and myofibroblastic differentiation of ASCs. This altered ASC phenotype led to varied extracellular matrix (ECM) deposition and contraction thereby enhancing tissue stiffness, a characteristic feature of breast tumors. Increased stiffness, in turn, facilitated changes in ASC behavior similar to those observed with tumor-derived chemical cues. Orthotopic mouse studies further confirmed the pathological relevance of ASCs in tumor progression and stiffness in vivo. In summary, altered ASC behavior can promote tumorigenesis and, thus, their implementation for regenerative therapy should be carefully considered in patients previously treated for cancer.     

Pericytes promote selective vessel regression to regulate vascular patterning

Blood vessel networks form in a 2-step process of sprouting angiogenesis followed by selective branch regression and stabilization of remaining vessels. Pericytes are known to function in stabilizing blood vessels, but their role in vascular sprouting and selective vessel regression is poorly understood. The endosialin (CD248) receptor is expressed by pericytes associated with newly forming but not stable quiescent vessels. In the present study, we used the Endosialin(-/-) mouse as a means to uncover novel roles for pericytes during the process of vascular network formation. We demonstrate in a postnatal retina model that Endosialin(-/-) mice have normal vascular sprouting but are defective in selective vessel regression, leading to increased vessel density. Examination of the Endosialin(-/-) mouse tumor vasculature revealed an equivalent phenotype, indicating that pericytes perform a hitherto unidentified function to promote vessel destabilization and regression in vivo in both physiologic and pathologic angiogenesis. Mechanistically, Endosialin(-/-) mice have no defect in pericyte recruitment. Rather, endosialin binding to an endothelial associated, but not a pericyte associated, basement membrane component induces endothelial cell apoptosis and detachment. The results of the present study advance our understanding of pericyte biology and pericyte/endothelial cell cooperation during vascular patterning and have implications for the design of both pro- and antiangiogenic therapies.     

A multicentre,prospective, randomised comparison of the sliding hip screw with the Medoff sliding screw and side plate for unstable intertrochanteric hip fractures

Objective

This study aimed to compare the dynamic hip screw (DHS) and Medoff sliding plate (MSP) for unstable intertrochanteric hip fractures.

Design

A randomised, prospective trial design was used.

Setting

The study was undertaken in two level-1 trauma centres and one community hospital.

Patients/participants

A total of 163 patients with unstable intertrochanteric hip fractures (Orthopaedic Trauma Association (OTA) 31-A2) were randomised to DHS or MSP. Inclusion and exclusion criteria were designed to focus on isolated unstable intertrochanteric hip fractures in ambulatory patients.

Intervention

Randomisation was performed intra-operatively, after placement of a 135° guide wire. Follow-up assessments were performed at regular intervals for a minimum of 6 months.

Main outcome measurements

The primary outcome measure was re-operation rate. The secondary outcome was patient function, evaluated using a validated outcome measure, the Hip Fracture Functional Recovery Score. Tertiary outcomes included: mortality, hospital stay, quality of reduction and malunion rate.

Results

A total of 86 patients were randomised to DHS and 77 to MSP. The groups had similar patient demographics, pre-fracture status and in-hospital course. The quality of reduction was the same for each group, but the operative time was longer in the MSP group (61.6 vs. 50.1 min, P = 0.01). The rate of re-operation was low (3/86 in DHS and 2/77 in MSP) with no statistically significant difference. The functional outcomes were the same for both groups, with functional recovery scores at 6 months of 51.0% in the DHS arm and 49.7% in the MSP arm.

Conclusions

The two techniques produced similar results for the clinically important outcomes of the need for further surgery and functional status of the patients at 6 months’ follow-up.     

Enhancing Care for Hospitalized Older Adults with Cognitive Impairment: A Randomized Controlled Trial

Background

Approximately 40% of hospitalized older adults have cognitive impairment (CI) and are more prone to hospital-acquired complications. The Institute of Medicine suggests using health information technology to improve the overall safety and quality of the health care system.

Objective

Evaluate the efficacy of a clinical decision support system (CDSS) to improve the quality of care for hospitalized older adults with CI.

Design

A randomized controlled clinical trial.

Setting

A public hospital in Indianapolis.

Population

A total of 998 hospitalized older adults were screened for CI, and 424 patients (225 intervention, 199 control) with CI were enrolled in the trial with a mean age of 74.8, 59% African Americans, and 68% female.

Intervention

A CDSS alerts the physicians of the presence of CI, recommends early referral into a geriatric consult, and suggests discontinuation of the use of Foley catheterization, physical restraints, and anticholinergic drugs.

Measurements

Orders of a geriatric consult and discontinuation orders of Foley catheterization, physical restraints, or anticholinergic drugs.

Results

Using intent-to-treat analyses, there were no differences between the intervention and the control groups in geriatric consult orders (56% vs 49%, P = 0.21); discontinuation orders for Foley catheterization (61.7% vs 64.6%, P = 0.86); physical restraints (4.8% vs 0%, P = 0.86), or anticholinergic drugs (48.9% vs 31.2%, P = 0.11).

Conclusion

A simple screening program for CI followed by a CDSS did not change physician prescribing behaviors or improve the process of care for hospitalized older adults with CI.

Electronic supplementary material

The online version of this article (doi:10.1007/s11606-012-1994-8) contains supplementary material, which is available to authorized users.KEY WORDS: cognitive impairment, clinical trial, decision support, hospitalized elders     

Intraoperative Diagnosis Using Sentinel Node Biopsy with Indocyanine Green Dye in Gastric Cancer Surgery: An Institutional Trial by Experienced Surgeons

Background

Reliable indicators that can intraoperatively determine the absence of nodal metastasis are in great demand to avoid unnecessary lymphadenectomy. However, little has been reported about the intraoperative diagnostic performance of sentinel node (SN) biopsy.

Methods

Sentinel node biopsy by subserosal or submucosal injection of indocyanine green (ICG) was performed in 241 patients with American Joint Committee on Cancer tumor, node, metastasis staging system, 7th edition, clinical T1 (n = 190) and T2 (n = 51) gastric cancer by two experienced surgeons. All nodes that stained green (green node, GN), representing SNs, were excised before gastrectomy and were sliced into 2-mm sections for intraoperative histological examinations with hematoxylin and eosin staining. The sliced GNs were also examined simultaneously by imprint cytology.

Results

The GNs were detectable in 240 patients (3.8 ± 2.4 nodes per patient; range 1–17 nodes; median 3 nodes), and the success rate of detection was 99.6 % (240 of 241). Of 240 patients with a successful detection, 29 were found to have lymph node (LN) metastases; 16 were diagnosed with LN metastases in both GNs and non-GNs, 12 in GNs alone, and 1 in non-GNs alone. The false-negative rate based on the SN concept was 3.4 % (1 of 29). However, two patients with cT1 gastric cancer were diagnosed as intraoperative GN negative but were later confirmed as GN positive by histological examinations of paraffin sections. As an intraoperative diagnosis, the false-negative rate was 10.3 % (3 of 29).

Conclusions

Sentinel node biopsy using ICG could be performed intraoperatively within reasonable limits under certain conditions, such as multiplanes for detection, combination use of imprint cytology, and open surgery by experienced surgeons.     

Crystalloids,colloids, blood,blood products and blood substitutes

Understanding the physiology of fluid distribution within the human body is fundamental to the practice of anaesthetists and intensivists of all grades. There is a necessity to recognize the range of actions and consequences of the commonly infused intravenous fluids if safe patient care is to be provided. There are many historical and on-going trials surrounding fluid therapy and it is important for the physician to keep up to date with current guidelines.There is a continued drive to improve the safety of donor blood and prevent transfusion errors. Knowledge of how blood products are collected separated and stored is essential to prevent harm to patients through transfusions. Work in producing blood substitutes is progressing, but to date, trials have failed to market a product in Europe and the USA with an acceptable risk profile.     

A psychometric study of recovery among Certified Peer Specialists

The recovery model is wielding a welcome influence in the mental healthcare system. Despite its potential impact, systematic studies of the recovery construct as viewed by consumers and former consumers of mental health services have only recently begun to permeate the literature. We have embarked on an ongoing collaboration with the Georgia Mental Health Consumer Network to study the recovery experiences of Certified Peer Specialists (CPSs). As a first step, we evaluated the psychometric characteristics of a new measure of the recovery construct in CPSs. CPSs (N=84) enrolled in the GMHCN completed the Maryland Assessment of Recovery in Serious Mental Illness (MARS) along with measures of resilience, coping styles, community living, social support, internalized stigma, psychopathology, and personality. Recovery as measured by the MARS was associated with resilience, coping behaviors, quality of social support, community living, internalized stigma, and severity of psychopathology. Recovery did not demonstrate a statistically significant association with personality. Recovery appeared to mediate the effect of psychopathology and episodic stressors on community functioning. Our psychometric study supports the psychometric soundness of the MARS and the construct validity of recovery.     

Bridging Hepatocellular Carcinoma to Transplant: Transarterial Chemoembolization Response,Tumor Biology,and Recurrence after Transplantation in a 12-Year Transplant Cohort

PurposeTo evaluate tumor response to transarterial chemoembolization as well as biologic characteristics of the tumor as predictors of recurrence after transplantation in patients with hepatocellular carcinoma (HCC) who were bridged or down-staged to liver transplantation.Materials and MethodsAn institutional review board-approved, Health Insurance Portability and Accountability Act-compliant, single-institution retrospective analysis was performed on all patients with HCC who were treated with the use of conventional transarterial chemoembolization or transarterial chemoembolization with drug-eluting embolics (DEE) over a 12-year period and who subsequently underwent liver transplantation (n = 142). Treatment response was based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) imaging criteria and then correlated with tumor characteristics and recurrence. Of the 142 patients followed after transplantation, 127 had imaging after transarterial chemoembolization but before transplantation. Imaging response and post-transplantation recurrence were correlated with patient demographics, liver function, and tumor morphology. HCC recurred in 9 patients (mean time from transplantation, 526 days). Recurrence was analyzed with the use of univariate and multivariate statistics. Kaplan-Meier recurrence-free survival curves were calculated based on immediate imaging response before transplantation with the use of the log-rank test.ResultsBefore transplantation, 57% of patients (72/127) demonstrated complete response (CR) and 24% (31/127) showed partial response (PR). Complete pathologic necrosis occurred in 54% (39/72) of CR patients and 20% (6/31) of PR patients. Poor treatment response, defined as stable disease (SD) or progressive disease (PD), occurred in 18% of patients (24/127) before transplantation and was present in 67% of cases of recurrence (6/9; P < .001). Post-transplantation recurrence was present in 1.4% of patients (1/71) with CR and in 6.5% of patients (2/31) with PR. In patients with SD after transarterial chemoembolization, HCC recurred in 18.8% of transplant patients (3/16) and in 43% of patients (3/7) with PD. Larger pretreatment tumor size (P = .05), higher Child-Pugh score (P = .002), higher tumor grade at explantation (P = .04), and lymphovascular invasion at explantation (P = .008) also were associated with increased incidence of post-transplantation recurrence.ConclusionsPoor tumor response to transarterial chemoembolization before transplantation identifies patients at increased risk for post-transplantation recurrence.