Multidisciplinary Care Considerations for Patients with Craniosynostosis.

Infants and children with craniosynostosis require multidisciplinary care, and this is best accomplished when care is provided on a craniofacial team. Most patients with craniosynostosis will have non-syndromic presentations; however, longitudinal care remains critical to ensure appropriate growth and development throughout childhood. In patients with syndromic craniosynostoses, coordinated longitudinal care becomes even more paramount because of the high level of complexity across many different specialties or disciplines. Care delivery that includes perspective and expertise from multiple disciplines is important to help patients reach their full potential and optimal outcomes.

A MultiCenter Pilot Randomized Controlled Trial of Remote Ischemic Preconditioning in Major Vascular Surgery.

A pilot randomized controlled trial that evaluated the effect of remote ischemic preconditioning (RIPC) on clinical outcomes following major vascular surgery was performed. Eligible patients were those scheduled to undergo open abdominal aortic aneurysm repair, endovascular aortic aneurysm repair, carotid endarterectomy, and lower limb revascularization procedures. Patients were randomized to RIPC or to control groups. The primary outcome was a composite clinical end point comprising any of cardiovascular death, myocardial infarction, new-onset arrhythmia, cardiac arrest, congestive cardiac failure, cerebrovascular accident, renal failure requiring renal replacement therapy, mesenteric ischemia, and urgent cardiac revascularization. Secondary outcomes were components of the primary outcome and myocardial injury as assessed by serum troponin values. The primary outcome occurred in 19 (19.2%) of 99 controls and 14 (14.1%) of 99 RIPC group patients (P = .446). There were no significant differences in secondary outcomes. Our trial generated data that will guide future trials. Further trials are urgently needed.

Three-dimensional computed tomographic reconstruction of the carotid artery: identifying high bifurcation.

OBJECTIVE: To investigate variability in the level of bifurcation relative to other anatomical landmarks on computed tomography (CT) and to develop an objective and reproducible technique for identifying patients with a high carotid bifurcation who might therefore be at greater risk of operative complications. METHODS: This was a retrospective cross-sectional, imaging study. A series of 86 nonselected consecutive CT carotid angiograms (172 arteries) were analysed. Using three-dimensional reconstructive software, the curved length (CL) of the internal carotid artery (ICA) and the straight-line distance (SLD) from the bifurcation to the base of skull was measured for 140 carotid arteries. The tortuosity index (TI) of each ICA was calculated by dividing CL by SLD. The relationship of the bifurcation to eight anatomical landmarks in the neck was assessed in order to identify a landmark that could act as a surrogate marker of high carotid bifurcation. The landmarks examined were the angle of mandible, greater horn of hyoid, body of hyoid, upper margin of thyroid cartilage, cervical vertebrae, mastoid process, sternoclavicular joint, and sternal notch. RESULTS: The median curved length of the ICA was 80.4 mm (range 58.0-129.0 mm). The median distance of bifurcation from the base of the skull was 72.7 mm (range 58.1-98.1 mm). There was excellent interobserver agreement in measuring SLD, with an intraclass correlation coefficient of 0.993 (p = .00). The median tortuosity index was 1.12 (range 1.01-1.64). Distance from the mastoid process had the greatest correlation with high bifurcation; Pearson's correlation coefficient of 0.894 (two-tailed p = .00). Bifurcations within 5 cm of the mastoid process are likely to be in the highest quartile (82.9% sensitive, 80.1% specific). CONCLUSIONS: Measuring the distance of carotid bifurcation from the base of the skull (SLD), a measure previously not well defined, may be useful in predicting difficult neck dissection and endarterectomy. A distance from mastoid of ≤ 5 cm may also alert the surgeon to potential difficulties.

"Is general surgery still relevant to the subspecialised trainee?" A 10 year comparison of general versus specialty surgical practice.

BACKGROUND: The splintering of general surgery into subspecialties in the past decade has brought into question the relevance of a continued emphasis on traditional general surgical training. With the majority of trainees now expressing a preference to subspecialise early, this study sought to identify if the requirement for proficiency in managing general surgical conditions has reduced over the past decade through comparison of general and specialty surgical admissions at a tertiary referral center. METHODS: A cross-sectional review of all surgical admissions at Cork University Hospital was performed at three individual time points: 2002, 2007 & 2012. Basic demographic details of both elective & emergency admissions were tabulated & analysed. Categorisation of admissions into specialty relevant or general surgery was made using International guidelines. RESULTS: 11,288 surgical admissions were recorded (2002:2773, 2007:3498 & 2012:5017), showing an increase of 81 % over the 10-year period. While growth in overall service provision was seen, the practice of general versus specialty relevant emergency surgery showed no statistically significant change in practice from 2002 to 2012 (p = 0.87). General surgery was mostly practiced in the emergency setting (84 % of all emergency admissions in 2012) with only 28 % elective admissions for general surgery. A reduction in length of stay was seen in both elective (3.62-2.58 bed days, p = 0.342) & emergency admissions (7.36-5.65, p = 0.026). CONCLUSIONS: General surgical emergency work continues to constitute a major part of the specialists practice. These results emphasize the importance of general surgical training even for those trainees committed to sub-specialisation.

ACE up the sleeve - are vascular patients medically optimized?

OBJECTIVE: To examine the current medical management of arteriopathic patients attending a vascular surgical service at a university teaching hospital over a 6-month period. The prescribing of antiplatelets, statins, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers and beta-blockers was specifically examined. Vascular patients are often under the care of multiple specialties, and therefore the influence of different medical specialties on the patients' medical management was also examined. DESIGN: Between January and June 2009, data were recorded on sequential patients with arterial disease attending the vascular surgical service. Patients' demographics, type of arterial disease, medical consultations within the previous 12 months, and current medications were recorded. RESULTS: The study included 180 patients with a mean age of 69 years (39-88 years). All but 4% were taking an antiplatelet or anticoagulant, predominantly aspirin. There were 86% taking a statin, 44% taking a beta-blocker, and 51% taking an ACE inhibitor. Suboptimal prescription of ACE inhibitors and beta-blockers was evident regardless of the type of medical consultations in the previous year. No specialty group differed significantly from vascular surgeons in their prescribing pattern. CONCLUSIONS: While almost all arteriopaths receive some form of antiplatelet and statin in line with clinical evidence, ACE inhibitors and beta-blockers appear to be under-prescribed in this arteriopathic population. We conclude that opportunity exists for vascular surgeons to embrace recent guidelines and lead the way in both surgical and medical optimization of arteriopathic patients through improving links with primary care physicians or taking greater responsibility themselves for the medical as well as the surgical care of their arteriopathic patients.

Popliteal artery entrapment syndrome.

Popliteal artery entrapment syndrome is a rare abnormality of the anatomical relationship between the popliteal artery and adjacent muscles or fibrous bands in the popliteal fossa. The following is a case report of a 19 year old female, in whom popliteal artery entrapment syndrome was diagnosed, and successfully treated surgically. A review of literature is also presented and provides details on how PAES is classified, diagnosed both clinically and radiologically, and treated surgically.

Atmospheric pressure variations and abdominal aortic aneurysm rupture.

BACKGROUND: Ruptured abdominal aortic aneurysm (RAAA) presents with increased frequency in the winter and spring months. Seasonal changes in atmospheric pressure mirrors this pattern. AIM: To establish if there was a seasonal variation in the occurrence of RAAA and to determine if there was any association with atmospheric pressure changes. METHODS: A retrospective cohort-based study was performed. Daily atmospheric pressure readings for the region were obtained. RESULTS: There was a statistically significant monthly variation in RAAA presentation with 107 cases (52.5%) occurring from November to March. The monthly number of RAAA and the mean atmospheric pressure in the previous month were inversely related (r = -0.752, r (2) = 0.566, P = 0.03), and there was significantly greater daily atmospheric pressure variability on days when patients with RAAA were admitted. CONCLUSION: These findings suggest a relationship between atmospheric pressure and RAAA.

Aortic dissections: new perspectives and treatment paradigms.

Aortic dissection is a complex manifestation of disease of the arterial wall. The severity and consequences of a dissection are related to the physical characteristics and anatomic location of the tear as well as the underlying patient physiology. Despite in vitro and in vivo modeling advances, our understanding of the pathophysiology has been limited to evaluations of the success and failure of various treatment modalities. The indications for intervention have historically included rupture, intractable pain or hypertension, distal ischemia and degeneration of the aortic wall causing aneurysm formation. The management decisions for patients with dissections are dependent upon the abnormal anatomy, the acuity of the patient presentation, and physiology. Despite the availability of open surgery as a therapeutic option, acute dissections with evidence of ischemia are now handled using an endovascular approach that is specifically directed at the cause of the ischemia. Endovascular treatments include the placement of a stentgraft into the proximal aorta, branch vessel stenting, uncovered stent placement in the abdominal aorta, and aortic fenestrations. Chronic dissections, in contrast, are still most frequently managed with open surgical techniques. However, a subset of patients that are not candidates for traditional surgical repair of the thoracoabdominal aorta may be managed with a combined open mesenteric revascularization with subsequent endovascular grafting of the thoracoabdominal aorta.

Combination therapy of cholesterol reduction and L-arginine supplementation controls accelerated vein graft atheroma.

Hyperlipidemia contributes to the development of intimal hyperplasia and accelerated atheroma in vein bypass grafts. Dietary cholesterol reduction and oral supplementation with L-arginine have been shown to reduce accelerated atheroma in experimental vein grafts. This study extends these observations by examining the effect of the combination therapy of cholesterol reduction and L-arginine supplementation on the development of intimal hyperplasia in vein grafts in hypercholesterolemic animals. Thirty New Zealand White rabbits had a carotid vein bypass graft performed and were sacrificed at 28 days postoperatively either for morphology (light and electron microscopy) and videomorphometry, or for in vitro contractile studies. Twenty animals received a 1% cholesterol diet for 4 weeks prior to surgery. This diet was continued until harvest in ten animals. Ten cholesterol-fed animals received L-arginine supplementation (2 g/kg/day, p.o.) for 7 days preoperatively and thereafter until harvest and in addition were returned to a normal diet on the day of surgery. The last ten animals were controls (normal diet). Combined cholesterol reduction and L-arginine supplementation prevented accelerated atheroma in vein grafts, halted the change in enhanced smooth muscle cell contractility, and improved endothelial cell function. Early postoperative therapy targeting atheroma development in the high-risk patient could offer significant morphological and functional benefits.

Early morphology of accelerated vein graft atheroma in experimental vein grafts.

Vein grafts fail because of the development of intimal hyperplasia and atheroma. Recent experimental evidence suggests that the presence of hypercholesterolemia induces a three-fold increase in intimal hyperplasia with early atheroma development within 4 weeks of implantation. We have previously demonstrated endothelial cell preservation and a short-lived (3-day) polymorphonuclear leukocyte infiltrate in vein grafts. The aim of this study is to define the early morphology and ultrastructure of vein grafts implanted into a hyperlipidemic environment to provide a pathological foundation on which to examine the cellular and molecular events that determine this accelerated response. Twenty-one male New Zealand White rabbits underwent a right carotid interposition bypass graft using the ipsilateral external jugular vein; all animals received a 1% cholesterol diet for 4 weeks prior to surgery and continuing postoperatively until harvest. Animals (n = 3 per time point) were sacrificed at 60 min, 1 day, 3 days, 5 days, 7 days, 14 days, and 28 days postoperatively for scanning and transmission electron microscopy of the vein grafts. No concurrent controls were employed. The results of this study suggest that in the presence of hypercholesterolemia, the pathophysiological processes involved in the vein graft are similar to those reported for noncholesterol-fed animals. There is a sustained subendothelial response with the prolonged presence of macrophages and cellular debris and the accumulation of foam cells.

Controlling transplant vasculopathy in cryopreserved vein grafts with polyethylene glycol and glutathione during transport.

BACKGROUND: the biological characteristics of cryopreserved allografts are poorly understood, although many factors are known to influence their outcome. This study examines the development of transplant vasculopathy in both fresh and cryopreserved vein allografts and specifically assesses the efficacy of a transport solution containing 10% polyethylene glycol and 10 microM glutathione (PEG/GSH). METHODS: jugular veins were harvested from control donor rabbits and transplanted as interposition carotid bypass grafts in 30 New Zealand White (NZW) rabbits. Ten received the fresh jugular veins (fresh). Ten animals received jugular veins which had been harvested, transported in a physiological solution, cryopreserved and stored in a standard fashion (cryopreserved). Ten animals received jugular veins which had been harvested, transported in the same solution with the addition of PEG/GSH, cryopreserved and stored in a standard fashion (PEG/GSH). Cryopreserved jugular veins were stored for 6 weeks before transplantation. All animals were sacrificed 28 days postoperatively. Vein grafts were perfusion-fixed and wall dimensions were determined by planimetry. RESULTS: all transplanted grafts were patent at harvest. The control cryopreserved vein grafts showed a 54% increase in mean intimal thickness (63+/-10 micron vs. 41+/-3 micron p<0.05) but no change in mean medial thickness (125+/-9 micron vs. 119+/-13 micron; p = N.S. ) compared to the fresh allograft. Transport of the grafts in PEG/GSH solution resulted in the abolition of the increase in intimal thickness (41+/-4 micron; p <0.01) associated with cryopreservation without a change in medial thickness (140+/-15 micron; p = N.S.) compared to the cryopreserved allograft. CONCLUSION: cryopreserved vein grafts develop significant intimal hyperplasia compared to freshly transplanted grafts. The use of PEG/GSH in the transport solution significantly reduces this transplant graft intimal hyperplasia to that which develops in fresh grafts and may lead to improvements in the clinical use of cryopreserved veins.

Laparoscopic-assisted and hand-access laparoscopic surgery.

Therapeutic laparoscopy has developed rapidly since the first report of laparoscopic cholecystectomy in 1986. Several other reports followed before the end of that decade. Recent developments have resulted from a combination of the many technical improvements in laparoscopic equipment, together with the innovation and increasing experience of those performing laparoscopic surgery. Cholecystectomy, appendectomy, gastric fundoplication, and preperitoneal hernia repair are all now widely practiced and often laparoscopy is the favored approach.

Time course of the regression of intimal hyperplasia in experimental vein grafts.

A previous study in which vein grafts were removed from the arterial circulation and reimplanted into the venous circulation of the same animal demonstrated regression of vein graft intimal hyperplasia and medial thickening within 14 days. The present study was designed to characterize the kinetics of the morphological and ultrastructural changes over this 14-day period. Twenty-one male New Zealand White rabbits received a reversed vein interposition bypass graft of the right common carotid artery. Fourteen days after the procedure, 21 vein grafts were isolated, removed, and reimplanted into the contralateral external jugular venous system as veno-venous interposition bypass grafts (reversal grafts). The grafts were harvested at 60 minutes, 1 day, 3 days, 5 days, 7 days, and 14 days after reversal. Before insertion into the venous circulation, the vein graft had a confluent endothelial cell surface with multiple layers of smooth muscle cells representing intimal hyperplasia. After 1 hour, the reversal graft retained an intact endothelial cell layer with no evidence of tissue edema or cellular disruption. By 24 hours, there were a few blood cells on the endothelial cell surface. There was no inflammatory infiltrate seen in the subendothelium, and the smooth muscle cells were unaltered. At 3 days, the endothelial cell lining remained intact with no polymorphonucleocytes in the subendothelium or within the graft wall. Underlying smooth muscle cells at this time were noted to contain cytoplasmic vacuoles. At 5 days, there were no inflammatory cells seen on the surface or within the vein graft wall, but many of the underlying smooth muscle cells within the intimal hyperplasia were noted to be fragmented and to have clumping of chromatin. After 7 days, the endothelial cells remained intact and there was widespread evidence of apoptosis beneath the subendothelium with highly fragmented smooth muscle cells, some of which were histologically in the process of breaking up. At 14 days, the grafts retained uniform endothelial cell surfaces. Most of the smooth muscle cells that composed the intimal hyperplasia seen before implantation as a reversal graft were gone. Areas of newly laid down collagen could be observed. There were no acute inflammatory cells but for some mast cells seen in the graft wall. This study demonstrates that in this model, regression of intimal hyperplasia was associated with apoptosis of the smooth muscle cells and the deposition of collagen. There was no evidence that this process is mediated by an acute inflammatory response. Regression therefore appears to be due to induction of smooth muscle cell apoptosis by either a reduction in pressure or flow or a combination of both factors. The findings will enable a systematic cellular and molecular analysis of the biology of regression, which may afford clues to better understand the biology of the developing intimal hyperplasia.

Locally applied antisense oligonucleotide to proliferating cell nuclear antigen inhibits intimal thickening in experimental vein grafts.

This study examines the effect of antisense oligonucleotide to proliferating cell nuclear antigen (PCNA) on the formation of vein graft intimal hyperplasia in vivo, using localized administration. Twenty-four New Zealand white rabbits had a right carotid interposition bypass graft using the external jugular vein and were sacrificed on the 28th postoperative day. To determine the effect of PCNA on the development of intimal hyperplasia, 6 animals had their grafts coated with a pluronic gel containing 18 base antisense oligonucleotide to PCNA (1 mg/ml), 6 received a pluronic gel containing an 18 base nonsense oligonucleotide (1 mg/ml), and 12 animals were controls (6 with and 6 without pluronic gel). These grafts were harvested for morphology and videomorphometry. There was no change in the intimal thickness between the control and gel-treated groups. (70 +/- 4 microm versus 72 +/- 4 microm; mean +/- s.e.m.; p = ns). The presence of nonsense oligonucleotide had no further effect. Antisense PCNA produced a 26% decrease in intimal thickness to 50 +/- 4 microm in the treated vein grafts (p < 0.03) without a change in medial thickness. This study shows that a local single application of antisense oligonucleotide to PCNA will reduce the intimal hyperplasia in experimental vein grafts over 28 days.

G protein signaling and vein graft intimal hyperplasia: reduction of intimal hyperplasia in vein grafts by a Gbetagamma inhibitor suggests a major role of G protein signaling in lesion development.

Vein grafting results in the development of intimal hyperplasia with accompanying changes in guanine nucleotide-binding (G) protein expression and function. Several serum mitogens that act through G protein-coupled receptors, such as lysophosphatidic acid, stimulate proliferative pathways that are dependent on the G protein betagamma subunit (Gbetagamma)-mediated activation of p21ras. This study examines the role of Gbetagamma signaling in intimal hyperplasia by targeting a gene encoding a specific Gbetagamma inhibitor in an experimental rabbit vein graft model. This inhibitor, the carboxyl terminus of the beta-adrenergic receptor kinase (betaARK(CT)), contains a Gbetagamma-binding domain. Vein graft intimal hyperplasia was significantly reduced by 37% (P<0.01), and physiological studies demonstrated that the normal alterations in G protein coupling phenotypically seen in this model were blocked by betaARK(CT) treatment. Thus, it appears that Gbetagamma-mediated pathways play a major role in intimal hyperplasia and that targeting inhibitors of Gbetagamma signaling offers novel intraoperative therapeutic modalities to inhibit the development of vein graft intimal hyperplasia and subsequent vein graft failure.

Alterations in collagen subtype III and IV protein in experimental venous bypass grafting.

OBJECTIVE: To examine changes in collagen III and IV protein during the development of intimal hyperplasia in experimental vein grafts. METHODS: Sixteen New Zealand White rabbits underwent reversed, jugular vein, interposition grafting of the carotid artery. Vessels were harvested 3, 7 or 28 days after operation and subjected to immunohistochemical examination and gelatinase assays. RESULTS: In control vein, collagen IV was expressed around adventitial blood vessels and throughout the endothelium. Compared with its presence in control veins, collagen IV protein was decreased in the endothelium in all 3-day vein grafts and undetectable in the endothelium and intima in 7-day vein grafts, but was present in the endothelium and intimal hyperplasia in 28-day vein grafts. In contrast, collagen III was absent from the endothelium of control vein and 3-day vein grafts, was present at low levels in the intima of 7-day vein grafts, but was absent from the endothelium and intimal hyperplasia in 28-day vein grafts. In 3-day vein grafts, areas of collagen IV loss colocalized to areas of leukocyte infiltration. Protein extracts from 3-day vein grafts contained a 72 kDa gelatinase. CONCLUSIONS: The presence and alterations of collagen protein in veins and vein grafts are subtype specific. Collagen III does not appear to be a normal component of intimal hyperplasia in vein grafts. The decrease in collagen IV protein in the endothelium of veins may be a component of the endothelial changes that follow bypass grafting, mediated by leukocytes, the induction of gelatinase activity, or both.

Local effects of nitric oxide supplementation and suppression in the development of intimal hyperplasia in experimental vein grafts.

OBJECTIVES: The universal response of vein grafts after insertion into the arterial circulation is the development of intimal hyperplasia; smooth muscle cell proliferation and connective tissue deposition, which may be modulated in part by dysfunctional endothelial nitric oxide (NO) metabolism. This study examines the effects of single dose, local application by pluronic gel of a NO donor, S-nitroso-N-acetylpenicillamine (SNAP) and an NO synthase inhibitor nitro-L-arginine methyl ester (L-NAME) on the formation of intimal hyperplasia. MATERIALS: Forty New Zealand white rabbits underwent jugular vein interposition grafting of the common carotid artery. DESIGN: Ten animals were controls, 10 animals had the outer surface of the vein graft coated with 30% pluronic gel (2.5 ml), and 10 each were immersed for 15 min prior to insertion in Ringer lactate containing 10(-3) M of SNAP or L-NAME and then had their vein grafts coated with 2.5 ml of gel containing either SNAP (10(-3) M) or L-NAME (10(-3) M), which allows for sustained delivery for up to 6 h. On the 28th post operative day, the animals were sacrificed and vein grafts were harvested for morphology by electron microscopy (SEM and TEM) and dimensional analysis by videomorphometry. RESULTS: All vein grafts developed intimal hyperplasia. On SEM the vein grafts had a confluent layer of endothelial cells with multiple layers of smooth muscle cells representing intimal hyperplasia in TEM. There were no demonstrable morphological differences between the four groups. Local treatment with SNAP produced a significant 36% decrease in mean intimal thickness (72 +/- 4 microns vs. 45 +/- 4 microns; mean +/- S.E.M.; p < 0.01) without a change in medial thickness compared to gel-only treated groups (58 +/- 6 microns vs. 61 +/- 7 microns; p = ns). Inhibition of NO synthase by L-NAME had no effect on the development of intimal hyperplasia (72 +/- 4 microns vs. 79 +/- 10 microns; p = ns); medial thickness was also unchanged. CONCLUSION: These data confirm the protective effect of NO in vascular injury and suggest that NO synthase activity is either absent or reduced to such a level that further inhibition in this short time course is not relevant to the pathophysiology of vein graft intimal hyperplasia.

Localized versus systemic angiotensin II receptor inhibition of intimal hyperplasia in experimental vein grafts by the specific angiotensin II receptor inhibitor L158,809.

BACKGROUND: This study examines the effect of the angiotensin II receptor (type 1) antagonist (L158,809) on the formation of vein graft intimal hyperplasia in vivo, by both localized and systemic administration. METHODS: Forty New Zealand White rabbits underwent carotid interposition bypass grafting with the external jugular vein and were killed on postoperative day 28. To determine the effect of L158,809 on the development of intimal hyperplasia, 10 animals received long-term oral therapy with L158,809 (10 mg/kg/day, begun 5 days before operation and continued until harvest), 10 animals underwent coating of the grafts with a pluronic gel containing L158,809 (10(-5) mol/L), and 20 animals were controls (10 with and 10 without pluronic gel). These grafts were harvested for either histologic analysis (n = 6 per group) or in vitro isometric tension studies to angiotensin II (n = 4 per group). RESULTS: Long-term oral treatment with L158,809 produced a 43% decrease in intimal thickness from 76 +/- 6 microns (mean +/- SEM) in the control animals to 43 +/- 7 microns in the treated vein grafts (p = 0.002). There was also a significant decrease (44%) in the medial thicknesses between the control (75 +/- 4 microns) and L158,809-treated (42 +/- 6 microns) vein grafts (p = 0.007). The contractile responses to angiotensin II were abolished in the vein grafts by long-term L158,809 therapy. Local application by gel of L158,809 produced a significant decrease (33%) in the intimal thickness (48 +/- 3 microns) but no change in medical thicknesses (76 +/- 6 microns) compared with control grafts. The contractile responses to angiotensin II were unchanged in the vein grafts by local L158,809 therapy. CONCLUSIONS: This study shows that a local single application of L158,809 will reduce the intimal response but not the medial response in vein grafts, whereas long-term treatment will reduce intimal hyperplasia and the medial response in experimental vein grafts. Therefore angiotensin II acting through AT1 receptors mediates a significant part of the intimal hyperplastic response in vein grafts that appears to involve two phases: an acute intimal response requiring short-term therapy and a long-term medial response that requires prolonged therapy.