How do I allocate blood products at the end of life? An ethical analysis with suggested guidelines

Blood products are scarce resources requiring prudent and reasoned allocation. The utilization of red blood cells and platelets in terminally ill patients can be complicated and requires guidelines tempered by individualized considerations. Representative cases are discussed in which blood products are requested or utilized by patients at the end of life. Relevant literature is reviewed and ethical issues pertaining to each case are discussed. A practical approach to blood product utilization at the end of life is suggested.     

Patterns of frontoparietal activation as a marker for unsuccessful visuospatial processing in healthy aging

Visuospatial abilities are sensitive to age-related decline, although the neural basis for this decline (and its everyday behavioral correlates) is as yet poorly understood. fMRI was employed to examine age-related differences in patterns of functional activation that underlie changes in visuospatial processing. All participants completed a brief neuropsychological battery and also a figure ground task (FGT) assessing visuospatial processing while fMRI was recorded. Participants included 16 healthy older adults (OA; aged 69–82 years) and 16 healthy younger adults (YA; aged 20–35 years). We examined age-related differences in behavioral performance on the FGT in relation to patterns of fMRI activation. OA demonstrated reduced performance on the FGT task and showed increased activation of supramarginal parietal cortex as well as increased activation of frontal and temporal regions compared to their younger counterparts. Performance on the FGT related to increased supramarginal gyrus activity and increased medial prefrontal activity in OAs, but not YAs. Our results are consistent with an anterior-posterior compensation model. Successful FGT performance requires the perception and integration of multiple stimuli and thus it is plausible that healthy aging may be accompanied by changes in visuospatial processing that mimic a subtle form of dorsal simultanagnosia. Overall, decreased visuospatial processing in OA relates to an altered frontoparietal neurobiological signature that may contribute to the general phenomenon of increasingly fragmented execution of behavior associated with normal aging.     

Mentorship in surgical training: a systematic review

Objective  

This review systematically examines the literature regarding mentor–mentee relationships in surgery.     

A murine model of neurofibromatosis type 1 tibial pseudarthrosis featuring proliferative fibrous tissue and osteoclast‐like cells

Neurofibromatosis type 1 (NF1) is a common genetic condition caused by mutations in the NF1 gene. Patients often suffer from tissue‐specific lesions associated with local double‐inactivation of NF1. In this study, we generated a novel fracture model to investigate the mechanism underlying congenital pseudarthrosis of the tibia (CPT) associated with NF1. We used a Cre‐expressing adenovirus (AdCre) to inactivate Nf1 in vitro in cultured osteoprogenitors and osteoblasts, and in vivo in the fracture callus of Nf1^flox/flox and Nf1^flox/? mice. The effects of the presence of Nf1^null cells were extensively examined. Cultured Nf1^null‐committed osteoprogenitors from neonatal calvaria failed to differentiate and express mature osteoblastic markers, even with recombinant bone morphogenetic protein‐2 (rhBMP‐2) treatment. Similarly, Nf1^null‐inducible osteoprogenitors obtained from Nf1 mouse muscle were also unresponsive to rhBMP‐2. In both closed and open fracture models in Nf1^flox/flox and Nf1^flox/? mice, local AdCre injection significantly impaired bone healing, with fracture union being <50% that of wild type controls. No significant difference was seen between Nf1^flox/flox and Nf1^flox/? mice. Histological analyses showed invasion of the Nf1^null fractures by fibrous and highly proliferative tissue. Mean amounts of fibrous tissue were increased upward of 10‐fold in Nf1^null fractures and bromodeoxyuridine (BrdU) staining in closed fractures showed increased numbers of proliferating cells. In Nf1^null fractures, tartrate‐resistant acid phosphatase–positive (TRAP+) cells were frequently observed within the fibrous tissue, not lining a bone surface. In summary, we report that local Nf1 deletion in a fracture callus is sufficient to impair bony union and recapitulate histological features of clinical CPT. Cell culture findings support the concept that Nf1 double inactivation impairs early osteoblastic differentiation. This model provides valuable insight into the pathobiology of the disease, and will be helpful for trialing therapeutic compounds. © 2012 American Society for Bone and Mineral Research     

Na+/H+ exchange inhibition and antioxidants lack additive protective effects after reperfusion injury in the working heterotopic rat heart isograft.

BACKGROUND: The utility of combining strategies of myocardial protection was studied in intact rat hearts subjected to 1 hour of ischemia and 40 minutes blood reperfusion. METHODS: Lewis rats (n = 48) were divided into 4 transplant groups. Twenty-four hearts were arrested by coronary perfusion with hypothermic Celsior solution at 60 mm Hg. The aortic valve was punctured to introduce volume into the left ventricle (LV), and the hearts were abdominally isografted. Animals were either given both the antioxidant probucol (300 mg/kg) and the sodium-hydrogen exchange inhibitor cariporide (5 mg/kg) (CP; n = 6), just cariporide (CAR; n = 6), just probucol (PROB; n = 6), or neither drug (CON; n = 6). After 40 minutes of blood reperfusion, transplanted hearts were rearrested. The control recipients' native hearts (native; n = 6) were also arrested. Postmortem LV compliance relations and myocardial water content (MWC) were measured. RESULTS: Grafts protected by probucol were significantly more compliant than controls and significantly less compliant than grafts protected by cariporide alone and with both cariporide and probucol (p = 0.0001, analysis of variance). Compliance relations for CP overlapped those for CAR. All grafts were less compliant than natives. MWC was significantly greater in controls and PROB than in natives. CONCLUSIONS: Pretreatment with cariporide in the setting of ischemia-reperfusion injury provides greater protection against the development of diastolic abnormalities than probucol when Celsior solution is used for both arrest and preservation. In this model, there is no advantage to combining the drugs, supporting the hypothesis that there is an overlapping mechanism of protection.     

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.

     

High-dose ibuprofen for reduction of striatal infarcts during middle cerebral artery occlusion in rats

OBJECT: Ibuprofen is an antiinflammatory drug that disrupts leukocyte-endothelial cell interactions by limiting expression of endothelial adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), also known as CD54. The authors hypothesized that ibuprofen could reduce the size of the infarct associated with transient focal ischemia by inhibition of ICAM-1 expression, and they evaluated its effects in rats treated with middle cerebral artery (MCA) occlusion. Ibuprofen treatment was compared with mild systemic hypothermia, which is known to be neuroprotective and is commonly used during neurosurgical procedures. METHODS: The maximum ibuprofen dose (240 mg/kg/day) that could be tolerated with no systemic toxicity was established in the initial experiments. In the efficacy experiment, rats were pretreated with vehicle, ibuprofen, or hypothermia (33 degrees C) prior to 2 hours of MCA occlusion; then their brains were harvested at 24 hours of reperfusion for histological studies. End-ischemic cerebral blood flow (CBF) was evaluated using [14C]iodoantipyrine autoradiography in additional cohorts. Expression of ICAM-1 within ischemic compared with nonischemic caudate nucleus and putamen (striatum) or cortex was evaluated using immunohistochemical studies. Compared with vehicle treatment, ibuprofen produced a 46.2% reduction (p = 0.01) in striatal infarcts, which was comparable to hypothermia (48.7% reduction, p = 0.02). Ibuprofen did not alter end-ischemic CBF in any region studied, and the ibuprofen treatment group had the lowest proportion of animals with marked ICAM-1 staining. CONCLUSIONS: Ibuprofen given in maximum tolerated doses reduces the striatal infarct size after focal cerebral ischemia. The neuroprotective mechanism does not work through preservation of intraischemic CBF and is consistent with inhibition of ICAM-1 expression; however, at the doses used in this study, other effects of ibuprofen on platelet and endothelial function are possible.