Search

To perform a province-wide evaluation of adult major traumas and determine the proportion of patients who met clinical and/or anatomical criteria for resuscitative endovascular balloon occlusion of the aorta (REBOA). This is a retrospective analysis of all major trauma patients (age > 16) presenting to the sole adult level 1 trauma centre in Nova Scotia over a 5-year period (2012–2017). Data were collected from the Nova Scotia Trauma Registry and medical charts. We identified potential REBOA candidates using either: (1) clinical criteria (primary survey, Focused Assessment with Sonography for Trauma, pelvic/chest X-ray); or (2) anatomical criteria (ICD-10-CA codes). Potential candidates with persistent hypotension were considered true REBOA candidates. Overall 2885 patients were included in the analysis, of whom 248 (8.6%) patients were in shock (including 106 transfer patients) and had their charts reviewed. A total of 137 patients met clinical criteria for REBOA; 44 (1.5%) had persistent hypotension 10–20 min into resuscitation and were considered true REBOA candidates. There were 59 patients who met anatomical criteria for REBOA, of whom 15 (0.5%) patients had persistent hypotension and were true REBOA candidates. The 15 REBOA candidates based on anatomical criteria also met clinical criteria for REBOA. In this registry-based retrospective analysis, 1.5% of adult major trauma patients Nova Scotia were REBOA candidates based on resuscitative clinical presentation, while 0.5% were candidates based on post hoc anatomical injury patterns. Our findings suggest that using clinical findings and bedside imaging modalities as criteria may overestimate the number of candidates for REBOA.

Objective The objective of this study was to evaluate the safety and effectiveness of single ProGlide use per bilateral access site for endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms. Methods A retrospective cohort study was performed for all elective percutaneous EVARs from November 2015 to December 2017 at the QEII Health Sciences Centre (Halifax, Nova Scotia, Canada). Exposure of interest was number of ProGlides used per access site, dichotomized into bilateral single ProGlide closure vs nonsingle ProGlide closure on at least one femoral arteriotomy. Outcomes included Valve Academic Research Consortium (VARC)-2 and Bleeding Academic Research Consortium (BARC) criteria. Groups were compared with Fisher exact test, analysis of variance, or Wilcoxon rank sum, as appropriate. Logistic regression was used to compare the effect of single ProGlide use on VARC-2 and BARC criteria. Results A total of 131 cases were included, of which 116 had bilateral single ProGlide use for access closure. Baseline characteristics including comorbidities and smoking status were compared between groups. Groups were similar for all characteristics except smoking status, with an increased proportion of former smokers in the nonsingle ProGlide group. There were 119 (90.8%) patients who had single ProGlide use on the right femoral artery and 121 (92.4%) on the left; 16 (12.2%) patients had ProGlide deployment issues. Median maximal right and left femoral sheath diameters were 16F (interquartile range [IQR], 16F-18F) and 14F (IQR, 14F-16F), respectively. Median length of stay was 1 day (IQR, 1-1 day). VARC-2 criteria occurred in 8 of 131 (6.11%) patients, 6 of 116 (5.17%) with bilateral single ProGlides and 2 of 15 (13.3%) with nonsingle ProGlides. BARC criteria occurred in 6 of 131 (4.58%) patients, 5 of 116 (4.31%) with bilateral single ProGlides and 1 of 15 (6.67%) with nonsingle ProGlides. Single ProGlide use was not associated with a difference in VARC-2 (odds ratio, 0.35; 95% confidence interval, 0.64-1.94) or BARC (odds ratio, 0.63; 95% confidence interval, 0.07-6.79) criteria. No patients developed pseudoaneurysms or required repeated intervention for bleeding. Conclusions Single ProGlide use per vascular access site in patients undergoing EVAR is a safe and effective method for access closure with sheath diameters up to and including 16F.

Older adults undergoing emergency abdominal surgery have significantly poorer outcomes than younger adults. For those who survive, the level of care required on discharge from hospital is unknown and such information could guide decision-making. The ELF (Emergency Laparotomy and Frailty) study aimed to determine whether preoperative frailty in older adults was associated with increased dependence at the time of discharge.The ELF study was a UK-wide multicentre prospective cohort study of older patients (65 years or more) undergoing emergency laparotomy during March and June 2017. The objective was to establish whether preoperative frailty was associated with increased care level at discharge compared with preoperative care level. The analysis used a multilevel logistic regression adjusted for preadmission frailty, patient age, sex and care level.A total of 934 patients were included from 49 hospitals. Mean(s.d.) age was 76·2(6·8) years, with 57·6 per cent women; 20·2 per cent were frail. Some 37·4 per cent of older adults had an increased care level at discharge. Increasing frailty was associated with increased discharge care level, with greater predictive power than age. The adjusted odds ratio for an increase in care level was 4·48 (95 per cent c.i. 2·03 to 9·91) for apparently vulnerable patients (Clinical Frailty Score (CFS) 4), 5·94 (2·54 to 13·90) for those mildly frail (CFS 5) and 7·88 (2·97 to 20·79) for those moderately or severely frail (CFS 6 or 7), compared with patients who were fit.Over 37 per cent of older adults undergoing emergency laparotomy required increased care at discharge. Frailty scoring was a significant predictor, and should be integrated into all acute surgical units to aid shared decision-making and discharge planning.Los adultos mayores sometidos a cirugía abdominal de urgencia tienen resultados significativamente peores que los adultos jóvenes. Para aquellos pacientes que sobreviven, el nivel de atención que requieren tras el alta hospitalaria se desconoce y esta información podría servir de guía en la toma de decisiones. El estudio ELF (Emergency Laparotomy and Frailty) tenía como objetivo determinar si la fragilidad preoperatoria en adultos mayores se asociaba con un aumento de la dependencia en el momento del alta. MÉTODOS: El estudio ELF era un estudio multicéntrico extenso efectuado en el Reino Unido (n = 49) que incluyó una cohorte prospectiva de 934 pacientes mayores ( 65 años) sometidos a laparotomía de urgencia durante marzo-junio de 2017. El objetivo fue establecer si la fragilidad preoperatoria aumentaba el nivel de asistencia en el momento del alta en comparación con el nivel de asistencia preoperatorio. Para el análisis se utilizó una regresión logística multinivel ajustada a características previas al ingreso: fragilidad, edad del paciente, género, y nivel de asistencia.La edad media de los pacientes fue 76,2 años (DE = 6,83), con un 57% de mujeres, un 20,2% de pacientes frágiles y un 37,4% de adultos mayores que presentaron un aumento en el nivel de asistencia en el momento del alta. Un aumento de la fragilidad se asoció con un incremento en el nivel de asistencia en el momento del alta (y mayor poder predictivo que la edad). La razón de oportunidades (odds ratio, OR) ajustada por el aumento del nivel de asistencia fue 4,48 (i.c. del 95% 2,03-9,91) para pacientes aparentemente vulnerables (Clinical Frailty Scale, CFS 4); 5,94 (i.c. del 95% 2,54-13,90) para aquellos ligeramente frágiles (CFS 5); y 7,88 (i.c. del 95% 2,97-20,79) para aquellos con fragilidad moderada o grave (CFS 6 and 7) en comparación con pacientes en buenas condiciones. CONCLUSIÓN: Este es el primer estudio que documenta que más del 37% de adultos mayores sometidos a laparotomía de urgencia precisaron un aumento en el nivel de asistencia en el momento del alta. La evaluación de la fragilidad debería integrarse en todas las unidades quirúrgicas de agudos para ayudar a compartir la toma de decisiones y los planes de tratamiento.

Background Social media has changed the way surgeons communicate worldwide, particularly in dissemination of trial results. However, it is unclear if social media could be used in recruitment to surgical trials. This study aimed to investigate the influence of Twitter in promoting surgical recruitment in The Emergency Laparotomy and Frailty (ELF) Study. Methods The ELF Study was a UK-based, prospective, observational cohort that aimed to assess the influence of frailty on 90-day mortality in older adults undergoing emergency surgery. A power calculation required 500 patients to be recruited to detect a 10% change in mortality associated with frailty. A 12-week recruitment period was selected, calculated from information submitted by participating hospitals and the numbers of emergency surgeries performed in adults aged > 65 years. A Twitter handle was designed (@ELFStudy) with eye-catching logos to encourage enrolment and inform the public and clinicians involved in the study. Twitter Analytics and Twitonomy (Digonomy Pty Ltd) were used to analyse user engagement in relation to patient recruitment. Results After 90 days of data collection, 49 sites from Scotland, England and Wales recruited 952 consecutive patients undergoing emergency laparotomy, with data logged into a database created on REDCap. Target recruitment (n = 500) was achieved by week 11. A total of 591 tweets were published by @ELFStudy since its conception, making 218,136 impressions at time of writing. The number of impressions (number of times users see a particular tweet) prior to March 20th 2017 (study commencement date) was 23,335 (343.2 per tweet), compared to the recruitment period with 114,314 impressions (256.3 per tweet), ending June 20th 2017. Each additional tweet was associated with an increase in recruitment of 1.66 (95%CI 1.36 to 1.97; p Conclusion The ELF Study over-recruited by nearly 100%, reaching over 200,000 people across the U.K. Branding enhanced tweet aesthetics and helped increase tweet engagement to stimulate discussion and healthy competition amongst clinicians to aid trial recruitment. Other studies may draw from the social media experiences of the ELF Study to optimise collaboration amongst researchers. Trial registration This study is registered online at www.clinicaltrials.gov (registration number NCT02952430) and has been approved by the National Health Service Research Ethics Committee.

We report renal salvage maneuvers after accidental bilateral renal artery coverage during endovascular aneurysm repair of an infrarenal abdominal aortic aneurysm. A 79-year-old man with an infrarenal abdominal aortic aneurysm was treated with endovascular aneurysm repair. Completion angiography demonstrated coverage of the renal arteries. Several revascularization techniques were attempted, including endograft repositioning and endovascular stenting through the femoral and brachial approach. The patient eventually underwent open splenorenal bypass with a Y Gore-Tex graft (W. L. Gore & Associates, Flagstaff, Ariz). After 3 months, computed tomography showed no evidence of endoleak and patent renal arteries. Renal function was well maintained, and the patient did not require dialysis.

Objectives Non-celiac gluten sensitivity (NCGS) is the presence of symptoms induced by gluten and relieved by a gluten-free diet (GFD) in patients without celiac disease or wheat allergy. Studies are mixed as to whether gluten is the main symptom trigger in patients with NCGS. Gluten immunogenic peptides (GIPs) in stool and urine are novel methods to monitor GFD compliance. Few studies have investigated their use in patients with NCGS. The aim of this study was to assess whether patients with NCGS have increased symptoms with gluten ingestion and to assess compliance with the GFD using stool and urine GIPs. Method This was a prospective, randomized, double-blinded crossover trial evaluating symptoms in patients with NCGS. Thirty patients with NCGS and 43 healthy controls were placed on a GFD. Patients received 0.5 or 2 g/d of gluten for 7 d each. The remaining weeks, they received placebo for a total of 4 wk. Symptoms were evaluated weekly using the Celiac Symptom Index (CSI). Urine and stool samples were collected weekly and measured for the detection of GIPs to detect exposure to gluten. Results There was no difference in symptom severity within the NCGS group whether receiving placebo or gluten (32.69 versus 31.54, P = 0.64). Patients with NCGS had significantly higher CSI scores at baseline than healthy controls. Patients with NCGS were less likely to have stool and urine GIPs than healthy patients. Conclusion Patients with NCGS were more adherent to the GFD based on stool and urine GIP results. Patients with NCGS had increased symptom severity at baseline compared with healthy controls. Neither group had significantly increased symptoms after ingestion of gluten.

Objective: This study aimed to document the prevalence of frailty in older adults undergoing emergency laparotomy and to explore relationships between frailty and postoperative morbidity and mortality. Summary Background Data: The majority of adults undergoing emergency laparotomy are older adults (≥65 y) that carry the highest mortality. Improved understanding is urgently needed to allow development of targeted interventions. Methods: An observational multicenter (n=49) UK study was performed (March–June 2017). All older adults undergoing emergency laparotomy were included. Preoperative frailty score was calculated using the progressive Clinical Frailty Score (CFS): 1 (very fit) to 7 (severely frail). Primary outcome measures were the prevalence of frailty (CFS 5–7) and its association to mortality at 90 days postoperative. Secondary outcomes included 30-day mortality and morbidity, length of critical care, and overall hospital stay. Results: A total of 937 older adults underwent emergency laparotomy: frailty was present in 20%. Ninety-day mortality was 19.5%. After age and sex adjustment, the risk of 90-day mortality was directly associated with frailty: CFS 5 adjusted odds ratio (aOR) 3.18 [95% confidence interval (CI), 1.24–8.14] and CFS 6/7 aOR 6·10 (95% CI, 2.26–16.45) compared with CFS 1. Similar associations were found for 30-day mortality. Increasing frailty was also associated with increased risk of complications, length of Intensive Care Unit, and overall hospital stay. Conclusions: A fifth of older adults undergoing emergency laparotomy are frail. The presence of frailty is associated with greater risks of postoperative mortality and morbidity and is independent of age. Frailty scoring should be integrated into acute surgical assessment practice to aid decision-making and development of novel postoperative strategies.

In Gram-positive bacteria, Sortase A (Srt A) is a critical cysteine transpeptidase that is responsible for recognizing and assembling surface virulence proteins through the recognition of a LPXTG (leucine, proline, X, threonine, and glycine, where X is any amino acid) signal. Mutants lacking genes for Srt A attenuate infections without affecting microbial viability. Here a series of 2-phenyl-benzofuran-3-carboxamide derivatives were synthesized and identified as potent Srt A inhibitors. Activity assays revealed that multiple compounds exhibited excellent inhibitory activity against Srt A compared with known Sortase A inhibitor pHMB (IC50=130μM). Structural activity relationships (SARs) demonstrated that the amide group at 3-position was essential for inhibitory activity. Replacement of the hydroxyl group at the 2-phenyl position of benzofuran with other substitutions such as a methoxyl, halogen or nitro group reduced the enzyme inhibitory activity in most cases. The compound Ia-22 was found to be the most potent inhibitor against the enzyme with an IC50 value of 30.8μM. Molecular docking studies showed Ia-22 shared similar binding pattern with substrate LPXTG in the binding pocket of Srt A (PDB: 2KID) including i-butyl stretching, L-shape pattern kinking, and H-bond interaction with Srt A functional site residues Cys184, Trp194 and Arg197.

Pathologists generally diagnose whether or not cervical cancer cells have the potential to spread to other organs and assess the malignancy of cancer through whole slide histopathology images using virtual microscopy. In this process, the morphology of nuclei is one of the significant diagnostic indices, including the size, the orientation and arrangement of the nuclei. Therefore, accurate segmentation of nuclei is a crucial step in clinical diagnosis. However, several challenges exist, namely a single whole slide image (WSI) often occupies a large amount of memory, making it difficult to manipulate. More than that, due to the extremely high density and variant shapes, sizes and overlapping nuclei, as well as low contrast, weakly defined boundaries, different staining methods and image acquisition techniques, it is difficult to achieve accurate segmentation. A method is proposed, comprised of two main parts to achieve lesion localization and automatic segmentation of nuclei. Initially, a U-Net model was used to localize and segment lesions. Then, a multi-task cascade network was proposed to combine nuclei foreground and edge information to obtain instance segmentation results. Evaluation of the proposed method for lesion localization and nuclei segmentation using a dataset comprised of cervical tissue sections collected by experienced pathologists along with comparative experiments, demonstrates the outstanding performance of this method.

Objective To compare postoperative morphine equivalent intake after open abdominal aortic aneurysm (AAA) repair among analgesic modalities: systemic analgesia (SA) only with no regional anesthesia, surgically positioned paravertebral catheter (PVC), and thoracic epidural analgesia (TEA). Methods This retrospective cohort study included patients undergoing elective open AAA at the Queen Elizabeth II Health Science Center, Halifax, Nova Scotia. Demographics, morphine equivalents, methods of analgesia administration, and outcomes data were collected on all patients from 2005 to 2016. Total morphine equivalent (MEQ) on postoperative days (PODs) 1, 2, and 3 were compared among patients with SA, PVC, and TEA. A multivariable zero-inflated log-linear regression was used to determine the association between analgesic modality and MEQ. Multivariable logistic regression models were used to determine associations between analgesic modality and postoperative pain, rates of discharge from intensive care within 1 day and opioid-related adverse events. Results The study cohort included 355 patients: 177 retroperitoneal and 178 transperitoneal repairs; 173 patients underwent SA, 117 PVC, and 65 TEA. On POD1, median MEQs were 984 (interquartile range [IQR], 342-1525) for SA, 89 (33-246) for PVC, and 49 (0-90) for TEA. On POD2, the median MEQs were 105 (IQR, 57-210) for SA, 45 (15-99) for PVC, and 30 (0-64) for TEA. On POD3, the median MEQs were 45 (IQR, 15-120) for SA, 30 (0-60) for PVC, and 10 (0-45) for TEA. On multivariable log-linear regression, compared with SA, PVC and TEA were associated with increased odds of receiving no opioids on POD1 (odds ratio [OR], 66.85; 95% confidence interval [CI], 17.49-255.57; and OR, 214.68; 95% CI, 60.20-766.38; respectively), POD 2 (OR, 6.97; 95% CI, 3.61-13.46; and OR, 28.73; 95% CI, 15.68-52.62; respectively), and POD 3 (OR, 3.93; 95% CI, 2.72-5.67; and OR, 4.68; 95% CI, 3.20-6.86; respectively). If patients did receive opioids, compared with SA, PVC and TEA were associated with decreased consumption on POD1 (RR, 0.22; 95% CI, 0.18-0.27; and RR, 0.16; 95% CI, 0.12-0.20; respectively), POD2 (RR, 0.50; 95% CI, 0.42-0.58; and RR, 0.46; 95% CI, 0.37-0.56; respectively), and POD3 (RR, 0.78; 95% CI, 0.66-0.93; and RR, 0.76; 95% CI, 0.63-0.93; respectively). Compared with SA, PVC was associated with earlier discharge from intensive care (OR, 2.75; 95% CI, 1.17-6.45) and TEA was not (OR, 1.12; 95% CI, 0.56-2.2). Compared with TEA, PVC was not associated with increased rate of opioid-related adverse events (OR, 0.44; 95% CI, 0.08-2.44). Conclusions PVC and TEA are associated with decreased MEQ compared with SA. PVC is associated with earlier discharge from intensive care compared with SA and similar rates of opioid-related adverse events compared with TEA. Paravertebral analgesia appears to be a safe and effective analgesic modality in patients undergoing retroperitoneal approach for abdominal aneurysm repair.

Paravertebral catheters are a well-established analgesic modality in thoracic surgery but have not been described in abdominal aortic surgery. We describe a simple, safe, and effective technique of paravertebral catheter insertion by the operative surgeon after a retroperitoneal abdominal aortic aneurysm repair. Once the aneurysm repair is complete, an extrapleural plane between the parietal pleura and the twelfth rib is created through blunt dissection. A catheter is advanced into the space percutaneously under direct vision, and a continuous infusion of local anesthetic is administered. Paravertebral catheters typically remain in place for 3 to 5 days and provide excellent postoperative non-narcotic analgesia.

Bovine colostrum (BC) is a commonly used food supplement in humans for both immune support and athletic performance enhancement; the latter effect has been attributed in some studies to an increase in the anabolic cytokine Insulin-like Growth Factor-1 (IGF-1). The aim of the present study was to determine the effect of BC supplementation on serum IGF-1 in racing horses. Five serum IGF-1 samples were collected from 12 horses in race training every 2 weeks over an 8-week period from November to January. Six horses received BC supplementation for 4 weeks, starting at the 2-week point. The expected seasonal IGF-1 decrease over the November to January study period was observed, but there was no effect of BC supplementation on serum IGF-1 concentrations as compared with the untreated controls.

A 42-year-old female is involved in a motor vehicle accident and presents with a number of injuries. She is hemodynamically stable and is found to have multiple rib fractures, a hemopneumothorax, and several uncomplicated long bone fractures. A CT scan of her chest reveals a traumatic injury to her proximal descending thoracic aorta with evidence of pseudoaneurysm formation and surrounding hematoma (Fig 1). The following debate attempts to resolve whether open repair remains the gold standard for the treatment of blunt thoracic aortic injuries.

Introduction: Evidence exists that an ideal bypass conduit should have a functional endothelial cell surface combined with mechanical properties similar to those of native arteries. We hypothesized that the effect of combined arterial levels of pulsatile shear stress, flow, and cyclic strain would enhance saphenous venous endothelial cell nitric oxide (NO) production, and that variations in these “ideal” conditions could impair this function. We studied NO production as a measure of endothelial function in response to different hemodynamic conditions. Methods: Human adult saphenous venous endothelial cells were cultured in 10-cm silicone tubes, similar in diameter (5 mm) and compliance (6%) to a medium-caliber peripheral artery (eg, popliteal). Tube cultures were exposed to arterial conditions: a combined pressure (120/80 mm/Hg; mean, 100 mm/Hg), flow (mean, 115 mL/min) and cyclic strain (2%), with a resultant pulsatile shear stress of 4.8 to 9.4 dyne/cm2 (mean, 7.1). Identical tube cultures were used to study variations in these conditions. Modifications of the system included a noncompliant system, a model with nonpulsatile flow, and a final group exposed to pulsatile pressure with no flow. NO levels were measured with a fluorometric nitrite assay of conditioned media collected at 0, 0.25, 0.5, 1, 2, and 4 hours. Experimental groups were compared with cells exposed to nonpulsatile, nonpressurized low flow (shear stress 0.1 dyne/cm2) and static cultures. Results: All experimental groups had greater rates of NO production than cells under static conditions (P < .05). Cells exposed to ideal conditions produced the greatest levels of NO. Independent decreases in compliance, flow, and pulsatility resulted in significantly lower rates of NO production than those in the group with these conditions intact (vs noncompliant P < .05, vs nonflow P < .05, and vs nonpulsatile P < .05). Conclusions: Our results show that in the absence of physiologically normal pulsatility, cyclic strain, and volume flow, endothelial NO production does not reach the levels seen under ideal conditions. Pulsatile flow and compliance (producing flow with cyclic stretch) play a key role in NO production by vascular endothelium in a three-dimensional hemodynamically active model. This correlates biologically with clinical experience linking graft inflow and runoff and the mechanical properties of the conduit to long-term patency. (J Vasc Surg 2001;33:1199-205.)

The Pipeline Embolization Device (ev3 Endovascular Inc, Plymouth, Minnesota) is a new endovascular device designed to exclude suitable intracranial aneurysms. A 56-year-old woman presented with a symptomatic 4.1-cm splenic artery aneurysm (SAA) that was successfully managed with a two-staged treatment plan involving selective segmental splenic artery embolization and subsequent deployment of a Pipeline Embolization Device across the aneurysm neck to exclude the aneurysm and maintain splenic perfusion.

Visceral ischemia-reperfusion injury (VI) contributes to adverse outcomes following the repair of thoracoabdominal aneurysms. Experiments were designed to determine whether a poly-adenosine diphosphate-ribose polymerase (PARP) inhibitor modulates indexes of metabolic function (mitochondrial activity), inflammatory cell activation, and tissue inflammation (lipopolysaccharide receptor CD14 messenger ribonucleic acid) following VI.129S1/SvImj mice were subjected to thoracic aortic occlusion followed by 48 hours of reperfusion. Normal saline was administered to 25 untreated control mice and PJ34 to 21 mice before and immediately after thoracic aortic ischemia-reperfusion. Sham mice (n = 13) underwent median sternotomy alone. At 48 hours, all animals were euthanized and tissues harvested for quantitative analysis.PJ34 improved intestinal (P.05) but not hepatic mitochondrial activity following reperfusion. CD14 messenger ribonucleic acid levels in liver (P.004), kidney (P.003), and spinal cord (P.03) tissue were less in PJ34-treated mice.PJ34 preserved the metabolic function of intestinal but not hepatic tissue during reperfusion. PJ34 uniformly decreased the expression of an important marker of inflammatory cell activation and tissue inflammation in visceral tissue following VI. PARP inhibitors may serve as a therapeutic modality to abrogate the stress response to VI.

Systemic inflammatory responses contribute to mortality after thoracoabdominal aneurysm repair. Poly adenosine diphosphate (ADP) ribose polymerase (PARP) activity is known to modulate inflammation in animal models of injury. The effect of the PARP inhibitor PJ34 and genetic deletion of PARP-1(PARP -/-) on the systemic inflammatory response after thoracic aortic ischemia reperfusion (TAR) is not known.In one group, all mice were subject to TAR followed by 48 hours of reperfusion. Treated mice (PJ, n=24) were given PJ34 IP; untreated mice (UN, n=41) received normal saline intraperitoneally. The number of mice in each group was selected to have a similar number of survivors by 48 hours. In a second group, sham animals were subjected to mediastinotomy alone (sham, n=10) without TAR, and were compared with mice with deletion of the PARP-1 isoform (PARP-1 -/-, n=11) subjected to TAR. Tissue extracts were assayed for keratinocyte derived chemokine and granulocyte colony stimulating factor. Serum was assayed for interleukin-6.PJ34 treatment decreased mortality throughout the experimental protocol. There were no mortalities in the sham operated mice or PARP -/- mice subjected to TAR. PJ34 treatment decreased serum levels of interleukin-6 (p=0.01) and hepatic levels of interleukin-6 mRNA when compared with untreated and PARP-/- mice (p0.01). Only liver and kidney cytokine levels were decreased by PJ34 treatment (p0.05). In PARP-/- mice subjected to TAR, tissue cytokine levels were not different from those in sham mice.PARP inhibition may represent a novel therapeutic approach to minimizing inflammatory sequelae after TAR.

ObjectiveSpinal cord injury (SCI) remains a source of morbidity after thoracoabdominal aortic reconstruction. These studies were designed to determine whether PJ34, a novel ultrapotent inhibitor of the nuclear enzyme poly(adenosine diphosphate ribose) polymerase (PARP) could modulate neurologic injury after thoracic aortic ischemia reperfusion (TAR) in a murine model of SCI.MethodsForty-one anesthetized male mice were subject to thoracic aortic occlusion (11 minutes) through a cervical mediastinotomy followed by 48 hours of reperfusion (TAR) under normothermic conditions. PJ34-treated mice (PJ, n = 12) were given 10 mg/kg PJ34 intraperitoneally 1 hour before ischemia and 1 hour after unclamping. The control group (UN, n = 21) received normal saline intraperitoneally 1 hour before ischemia and 1 hour after unclamping. Sham animals (n = 10) were subject to thoracic aortic exposure with no aortic clamping and similar intraperitoneal normal saline injections. PARP-1−/− (KO, n = 8) mice were subjected to the same conditions as the UN mice. Blinded observers rated murine neurologic status after TAR by using an established rodent paralysis scoring system. Murine spinal cords were subjected to cytokine (GRO-1) protein analysis as a marker of inflammation and immunohistochemical analysis (hematoxylin-eosin and PAR staining). Paralysis scores (PS) and GRO-1 levels were compared with analysis of variance, and survival data were compared with χ2.ResultsImmediately after TAR, UN and PJ mice had severe neurologic dysfunction (PS = 5.8 ± 0.1 and 4.6 ± 0.6, respectively; P > .05), which was significantly worse than the KO mice (PS = 1.0 ± 0.7, P < .001). After 6, 24, and 48 hours KO mice had no discernable neurologic injury (PS = 0). Six hours after TAR, PJ mice significantly improved (PS = 1.1 ± 0.73, P < .001) and remained improved at 24 (PS = 0.7 ± 0.6) and 48 hours (PS = 0.6 ± 0.6). UN mice did not improve their PS, and Sham mice showed no neurologic abnormality at any time during these experiments. The mortality at 48 hours was 0% for PJ and KO mice, 43% for UN (P = .012), and 0% for Sham. GRO-1 levels were significantly decreased in PJ and KO versus UN mice (UN, 583 ± 119 vs PJ, 5.8 ± 0 vs KO, 5.3 ± 1.4 mg/pg; P < .0001). Immunohistochemistry showed evidence of decreased PAR staining and ventral motor neuron injury in PJ mice.ConclusionsGenetic deletion of PARP or inhibition of its activity (PJ34) rescued neurologic function in mice subjected to TAR. PARP inhibition might represent a novel therapeutic approach for prevention of SCI after TAR.Clinical relevanceBecause paralysis caused by spinal cord ischemia remains a serious complication of thoracic aortic aneurysm repair, effective therapeutic strategies to prevent or decrease its incidence are desirable. Although there is hope that the systemic complications associated with open thoracic aortic aneurysm repair will be avoided by managing these lesions with catheter-based endovascular approaches, the initial experiences suggest that spinal cord ischemia might continue to be an unresolved clinical problem.

Giant coronary artery aneurysms are rare in adults and are usually found in association with Kawasaki's disease arising in childhood. We report a case of a thrombosed giant right coronary artery aneurysm presenting as an intracardiac mass detected after inferior wall myocardial infarction. Histologic analysis indicated that fibromuscular dysplasia was the underlying cause of the aneurysm.

Introduction: Vascular endothelial growth factor (VEGF) has been implicated as a tissue protective agent following ischemia reperfusion. We have demonstrated that poly-ADP ribose polymerase (PARP) blockade prevented spinal cord dysfunction and improved survival following murine thoracic aortic ischemia reperfusion (TAR). Because renal and cardiac derangements are a significant source of morbidity following TAR, experiments were designed to examine the potential protective effect of PARP inhibition on VEGF expression and renal and cardiac tissue injury. Methods: Mice (n = 23) were subjected to 11 minutes of TAR. Animals were treated 1 hr prior to and 1 hr after surgery with either saline (Control, n = 8, 0.5 mL saline IP) or PARP inhibitor (PJ34, n = 10, PJ34 10 mg/kg IP). MS (n = 5) mice underwent median sternotomy without TAR. At 48 hours, surviving mice (n = 13) were sacrificed. Serum, kidney and cardiac tissues were subjected to VEGF analysis (ELISA) and tissue viability index determined (MTT assay, expressed as % sham). Results: PARP inhibition resulted in increased serum, renal and cardiac VEGF levels and improved renal viability (table, ∗p Table 1 . Serum, renal and cardiac VEGF, renal and cardiac viability index Serum VEGF (pg/mL) Renal VEGF (pg/mg) Renal viability index (%) Cardiac VEGF (pg/mg) Cardiac viability index (%) MS (5) 56.8 ± 5.3 52.8 ± 5.4 83.6 ± 9.5 25.3 ± 2.9 102.7 ± 6.7 Control (5) 152.6 ± 49.9 18.0 ± 3.4 75.8 ± 2.2 17.8 ± 1.4 90.1 ± 4.1 PJ34 (8) 1977.4 ± 571.1 + 36.1 ± 4.0 ∗∗ 116.5 ± 9.5 ∗ 34.1 ± 3.0 ∗ 86.7 ± 2.3 ∗ p ∗∗ p + p Conclusions: In the setting of TAR, PARP inhibition markedly increases serum VEGF and prevents a decrease in renal and cardiac VEGF levels. These higher VEGF levels coincide with an improvement in renal viability index and suggest that PARP inhibition may represent a novel therapeutic approach to the preservation of renal function in the setting of TAR.

Objective. —To evaluate the persistence of effects on health and development at age 5 years of the Infant Health and Development Program, an early childhood intervention that was provided to low-birth-weight (LBW) premature infants from neonatal discharge through age 3 years. Design. —Randomized, controlled, multicenter trial, stratified by two LBW groups: lighter (≤2000 g) and heavier (2001 to 2500 g). Setting. —Eight socioeconomically heterogeneous clinical sites. Participants. —Of 985 eligible infants weighing 2500 g or less and at 37 weeks' or less gestational age, 377 infants were randomly assigned to the intervention group and 608 to the follow-up only group. About two thirds of the infants in each group were in the lighter LBW stratum, and one third were in the heavier LBW stratum. Intervention. —The intervention group received home visits (from neonatal discharge through age 3 years) as well as center-based schooling (from 1 to 3 years of age). Children in both groups received pediatric surveillance. Main Outcome Measures. —Cognitive development, behavioral competence, and health status. Results. —At age 5 years, the intervention group had full-scale IQ scores similar to children in the follow-up only group. However, in the heavier LBW stratum, children in the intervention group had higher full-scale IQ scores (3.7 points higher;P=.03) and higher verbal IQ scores (4.2 points higher;P=.02). No significant differences between intervention and follow-up only groups in cognitive measures at age 5 years were noted in the lighter LBW infants. The intervention and follow-up groups were similar in behavior and health measures regardless of LBW stratum. Conclusion. —The early childhood intervention provided in the first 3 years of life had effects on heavier LBW premature infants' IQ and verbal performance at age 5 years that were not observed for lighter LBW premature infants. The intervention did not affect health or behavior at age 5 years in either LBW stratum. (JAMA. 1994;272:1257-1262)

education, counseling, anticipatory guidance, and continuity of care. Herein we evaluate the existing literature for the effectiveness of these strategies in meeting these goals. The emphasis in this discussion is on the clinicianpatient interaction. The underlying assumption is that the clinician's time is a valuable commodity that should be utilized in the most efficient manner. The clinical content areas included are physical evaluation, advice on physical concerns, parenting advice, parent-child interaction, and developmental advice. The effectiveness of current standards and issues for research are discussed in each of these areas. Certain topics relevant to child-health supervisior~, such as screening for disease or the use of physician extenders, are not discussed.

We studied compensatory growth and caloric intake during an accelerated growth period of ten infants with severe failure to thrive (FTT). The mean age at diagnosis was 7.1 months (range 1.5 to 16.0 months). The average percentage of normal weight for age in this group was 54.9%, mean length was 58 cm (86% normal for age), and the mean head circumference was 39.7 cm (92% normal for age). Compensatory growth rebound was completed after 6.2 months (range 3.5 to 9.0 months). Minimal calorie counts during peak rate of growth averaged 187 kcal/kg/day (range 147 to 213). The final group average percentage of normal weight for age was 95.5%, an increase of 40%. The group of rebounding infants gained 31 gm/day. The group's length increased to 94% of that expected for age and head circumference to 98% of that expected for age. Like malnourished infants, these with FTT had compensatory growth when managed with ad libitum caloric intake equal to twice the expected intake.