Laser interstitial thermal therapy has been used as an ablative treatment for glioma; however, its development was limited due to technical issues. The NeuroBlate System incorporates several ...technological advances to overcome these drawbacks. The authors report a Phase I, thermal dose-escalation trial assessing the safety and efficacy of NeuroBlate in recurrent glioblastoma multiforme (rGBM).
Adults with suspected supratentorial rGBM of 15- to 40-mm dimension and a Karnofsky Performance Status score of ≥ 60 were eligible. After confirmatory biopsy, treatment was delivered using a rigid, gas-cooled, side-firing laser probe. Treatment was monitored using real-time MRI thermometry, and proprietary software providing predictive thermal damage feedback was used by the surgeon, along with control of probe rotation and depth, to tailor tissue coagulation. An external data safety monitoring board determined if toxicity at lower levels justified dose escalation.
Ten patients were treated at the Case Comprehensive Cancer Center (Cleveland Clinic and University Hospitals-Case Medical Center). Their average age was 55 years (range 34-69 years) and the median preoperative Karnofsky Performance Status score was 80 (range 70-90). The mean tumor volume was 6.8 ± 5 cm(3) (range 2.6-19 cm(3)), the percentage of tumor treated was 78% ± 12% (range 57%-90%), and the conformality index was 1.21 ± 0.33 (range 1.00-2.04). Treatment-related necrosis was evident on MRI studies at 24 and 48 hours. The median survival was 316 days (range 62-767 days). Three patients improved neurologically, 6 remained stable, and 1 worsened. Steroid-responsive treatment-related edema occurred in all patients but one. Three had Grade 3 adverse events at the highest dose.
NeuroBlate represents new technology for delivering laser interstitial thermal therapy, allowing controlled thermal ablation of deep hemispheric rGBM. CLINICAL TRIAL REGISTRATION NO.: NCT00747253 ( ClinicalTrials.gov ).
The goals of our study were to determine the technical feasibility of dynamic MR lymphangiography for detecting sentinel lymph nodes using Gadomer-17 contrast material to compare these results to the ...clinically standardized blue dye contrast agent, and to show MR imaging-guided needle localization marking of the sentinel nodes.
Six anesthetized swine underwent MR imaging before and for 1 hr after interstitial injection of Gadomer-17 in the posterior tongue and intradermally in the stifle (knee). Using MR imaging guidance, we percutaneously placed a histology needle into the sentinel node or nodes. A standardized intraoperative sentinel node detection procedure was then performed using isosulfan blue contrast agent. Sentinel nodes identified on the MR images were compared with and matched to those identified by biopsy needle localization and the isosulfan blue contrast agent. RESULTS. Interstitial and intradermal injection of Gadomer-17 resulted in a lasting, increased MR signal in the regional lymph nodes. Seven sentinel nodes were identified in both the neck and the groin, with one pig showing two sentinel nodes in the neck and another showing two sentinel nodes in the groin. In all cases, the isosulfan blue contrast agent agreed with the location of the sentinel node determined by Gadomer-17 and marked with the needle.
In this large animal model, dynamic MR angiography of sentinel lymph nodes is technically feasible using a contrast agent (Gadomer-17) and can be easily combined with MR imaging-guided needle localization.
The activation and fusion of macrophages and of osteoclasts require the adaptor molecule DNAX-activating protein of 12 kD (DAP12), which contains immunoreceptor tyrosine-based activation motifs ...(ITAMs). TREM2 (triggering receptor expressed on myeloid cells-2) is the main DAP12-associated receptor in osteoclasts and, similar to DAP12 deficiency, loss of TREM2 in humans leads to Nasu-Hakola disease, which is characterized by bone cysts and dementia. Furthermore, in vitro experiments have shown that deficiency in DAP12 or TREM2 leads to impaired osteoclast development and the formation of mononuclear osteoclasts. Here, we demonstrate that the ligation of TREM2 activated phosphatidylinositol 3-kinase (PI3K), extracellular signal-regulated kinase 1 (ERK1) and ERK2, and the guanine nucleotide exchange factor Vav3; induced the mobilization of intracellular calcium (Ca(2+)) and the reorganization of actin; and prevented apoptosis. The signaling adaptor molecule DAP10 played a key role in the TREM2- and DAP12-dependent recruitment of PI3K to the signaling complex. Src homology 2 (SH2) domain-containing inositol phosphatase-1 (SHIP1) inhibited TREM2- and DAP12-induced signaling by binding to DAP12 in an SH2 domain-dependent manner and preventing the recruitment of PI3K to DAP12. These results demonstrate a previously uncharacterized interaction of SHIP1 with DAP12 that functionally limits TREM2- and DAP12-dependent signaling and identify a mechanism through which SHIP1 regulates key ITAM-containing receptors by directly blocking the binding and activation of PI3K.
Health care providers and system administrators are in the midst of a paradigm shift; moving from paternalism toward an egalitarian approach. For patient centred care to occur, health care providers ...must prioritize patient needs; provide information regarding treatments while taking patient preferences and expectations into account. While there is literature regarding patient centredness, there is less information from the patient perspective about the experience of being a patient and the influence on behaviour. Using phenomenological research methods and the theory of planned behaviour as a theoretical framework, this study addressed the questions, a) what is the essence of being a primary health care patient, and b) what influence do beliefs, attitudes, and experience have on people’s behaviour as a patient? Nineteen individuals participated. Seven shared elements of being a primary health care patient were identified and contributed to the development of a composite vignette. The patient experience was a socially oriented, governed and reinforced cyclical process. Patients described themselves as actively engaged in their health care – “working the system” to get what they needed, when they needed it. Patients changed their beliefs, attitudes and behaviour as a result of experiences with their physicians, and their perceived success or failure in acquiring the best health care possible. Being a patient was not a single, observable behaviour, but rather a set of contextually dependent strategies patients’ directed at the specific goal of getting the best healthcare possible. The theory of planned behaviour was unsuitable for understanding patients’ beliefs, attitudes and behaviour.
To determine whether transfused colorectal surgery patients were at increased risk for postoperative infections in a tertiary care teaching hospital and whether transfusion alone was the only ...significant risk factor.
A retrospective study.
A single tertiary care teaching hospital.
All patients admitted to St. Boniface General Hospital, Winnipeg, for colorectal surgery during the period Apr. 1, 1995, through Mar. 31, 1996, were studied (N = 154).
The overall infection rate was 17%: nontransfused patients, 13%, and transfused patients, 28% (p < 0.038). Patients who received albumin perioperatively had a significantly higher infection rate (38%) than those who did not (13%) (p < 0.001). Stepwise logistic regression analysis identified transfusion and albumin administration as the only independent risk factors for postoperative infection.
Perioperative transfusion or albumin administration significantly increases the risk of postoperative infection in colorectal surgery patients.
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