Oncolytic DNX-2401 Virus for Pediatric Diffuse Intrinsic Pontine Glioma.

BACKGROUND: Pediatric patients with diffuse intrinsic pontine glioma (DIPG) have a poor prognosis, with a median survival of less than 1 year. Oncolytic viral therapy has been evaluated in patients with pediatric gliomas elsewhere in the brain, but data regarding oncolytic viral therapy in patients with DIPG are lacking. METHODS: We conducted a single-center, dose-escalation study of DNX-2401, an oncolytic adenovirus that selectively replicates in tumor cells, in patients with newly diagnosed DIPG. The patients received a single virus infusion through a catheter placed in the cerebellar peduncle, followed by radiotherapy. The primary objective was to assess the safety and adverse-event profile of DNX-2401. The secondary objectives were to evaluate the effect of DNX-2401 on overall survival and quality of life, to determine the percentage of patients who have an objective response, and to collect tumor-biopsy and peripheral-blood samples for correlative studies of the molecular features of DIPG and antitumor immune responses. RESULTS: A total of 12 patients, 3 to 18 years of age, with newly diagnosed DIPG received 1×1010 (the first 4 patients) or 5×1010 (the subsequent 8 patients) viral particles of DNX-2401, and 11 received subsequent radiotherapy. Adverse events among the patients included headache, nausea, vomiting, and fatigue. Hemiparesis and tetraparesis developed in 1 patient each. Over a median follow-up of 17.8 months (range, 5.9 to 33.5), a reduction in tumor size, as assessed on magnetic resonance imaging, was reported in 9 patients, a partial response in 3 patients, and stable disease in 8 patients. The median survival was 17.8 months. Two patients were alive at the time of preparation of the current report, 1 of whom was free of tumor progression at 38 months. Examination of a tumor sample obtained during autopsy from 1 patient and peripheral-blood studies revealed alteration of the tumor microenvironment and T-cell repertoire. CONCLUSIONS: Intratumoral infusion of oncolytic virus DNX-2401 followed by radiotherapy in pediatric patients with DIPG resulted in changes in T-cell activity and a reduction in or stabilization of tumor size in some patients but was associated with adverse events. (Funded by the European Research Council under the European Union's Horizon 2020 Research and Innovation Program and others; EudraCT number, 2016-001577-33; ClinicalTrials.gov number, NCT03178032.).

Changes in the Thickness of Rat Nerve Sheaths after Single Subperineural Administration of Rat Bone Marrow Mesenchymal Stem Cells.

The sheaths of the damaged peripheral nerve of Wistar-Kyoto rats were studied after single subperineural administration of bromodeoxyuridine (BrdU)-labeled bone marrow mesenchymal stem cells (MSC) from the same rats. The sciatic nerve was damaged by ligation for 40 sec directly before MSC administration. BrdU+ MSC were identified in the recipient nerve within 1 week after transplantation and were detected not only in the endoneurium, but also in the epineurium and perineurium. It was found that single administration of MSC into the damaged nerve trunk led to an almost 2-fold increase in the thickness of its sheaths (perineurium and epineurium) in comparison with the control group (ligation). It can be hypothesized that MSC induce thickening of nerve sheaths through the production of factors that stimulate angiogenesis and adipogenesis.

Case Report: Combined Intra-Lesional IL-2 and Topical Imiquimod Safely and Effectively Clears Multi-Focal, High Grade Cutaneous Squamous Cell Cancer in a Combined Liver and Kidney Transplant Patient.

Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer worldwide, with ever increasing incidence and mortality. While most patients can be treated successfully with surgical excision, cryotherapy, or radiation therapy, there exist a subset of patients with aggressive cSCC who lack adequate therapies. Among these patients are solid organ transplant recipients who due to their immunosuppression, develop cSCC at a dramatically increased rate compared to the normal population. The enhanced ability of the tumor to effectively undergo immune escape in these patients leads to more aggressive tumors with a propensity to recur and metastasize. Herein, we present a case of aggressive, multi-focal cSCC in a double organ transplant recipient to frame our discussion and current understanding of the immunobiology of cSCC. We consider factors that contribute to the significantly increased incidence of cSCC in the context of immunosuppression in this patient population. Finally, we briefly review current literature describing experience with localized therapies for cSCC and present a strong argument and rationale for consideration of an IL-2 based intra-lesional treatment strategy for cSCC, particularly in this immunosuppressed patient population.

Ropivacaine continuous wound infusion after mastectomy with immediate autologous breast reconstruction: A retrospective observational study.

ABSTRACT: Continuous wound infusion usually provides postoperative analgesia as a multimodal analgesia with systemic opioid use. When continuous wound infusion of local anesthetics (LA) supports successful postoperative analgesia without systemic opioid use, the side effects of opioid can be reduced. Nevertheless, continuous wound infusion after mastectomy with immediate autologous breast reconstruction leads to concerns about wound healing. This study evaluated analgesic effects and wound healing conditions of continuous wound infusion of LA compared with opioid-based, intravenous patient-controlled analgesia (IV PCA) in mastectomy with immediate autologous breast reconstruction.This retrospective observational study included females, aged between 33 and 67 years, who underwent mastectomy with immediate autologous breast reconstruction. Sixty-five patients were enrolled. The eligible patients were placed into 2 groups for managing postoperative pain, one used continuous wound infusion with 0.5% ropivacaine (ON-Q, n = 32) and the other used a fentanyl-based IV PCA (IV PCA, n = 33). Using the electronic medical record system, the postoperative recovery profiles were examined over 5 days using a visual analogue scale (VAS), incidence of postoperative nausea and vomiting (PONV), incidence of sleep disturbance, frequency of rescue analgesic use, analgesia-related adverse events, length of hospital stay, and degree of patient satisfaction. The condition of the surgical wound was observed for 1 year after surgery.The primary endpoint was the intensity of pain at 6 hours after surgery. The VAS was comparable between the groups (P > .05). Although recovery profiles and the degree of patient satisfaction were similar between the groups, the incidence of PONV was significantly lower in the ON-Q group than in the IV PCA group on the day of surgery and postoperative day 1. No patients had severe wound complications. The satisfaction score of analgesia in the ON-Q group was comparable with that of the patients in the IV PCA group.This study demonstrates that single use of continuous wound infusion showed comparable analgesia with fentanyl-based IV PCA in patients who underwent mastectomy with immediate autologous breast reconstruction. Furthermore, the continuous infusion of LA directly on the surgical site did not significantly affect wound healing.

Postoperative Pain Treatment With Continuous Local Anesthetic Wound Infusion in Patients With Head and Neck Cancer: A Nonrandomized Clinical Trial.

Importance: Up to 80% of patients with head and neck cancer undergoing ablative surgery and neck dissection develop postoperative pain with detrimental effects on quality of life that also contributes to neuropathic and chronic postoperative pain. Objective: To investigate the association of continuous local anesthetic wound infusion with pain management after head and neck surgery. Design, Setting, and Participants: This prospective, longitudinal, nonrandomized clinical study carried out in a single tertiary referral center (December 1, 2015, to July 1, 2017) included 2 groups of 30 patients. Patients were consecutively enrolled and presented for ablative head and neck surgery including selective neck dissection and studied from the preoperative through the fourth postoperative day. Interventions: The control group was treated according to a standardized escalating oral treatment protocol (ibuprofen, metamizole, opioids). The intervention group was treated with an intraoperatively applied pain catheter (InfiltraLong plus FuserPump, Pajunk, ropivacaine, 0.2%, 3 mL/h) that was removed 72 hours after operating. Main Outcomes and Measures: Average and maximum pain intensities on a numeric rating scale; quality of life using the acute version of the validated 36-Item Short Form Survey; and neuropathic pain using the validated 12-Item painDETECT questionnaire. Consumption of opioid and nonopioid analgesics and evaluation of catheter-associated complications. Results: During postoperative days 1 through 4, patients of the intervention group (mean [SD] age, 63.2 [13.3 years; 9 [30%] women) experienced lower mean (SD) (1.6 [1.4] vs 2.7 [1.8]; η2p = 0.09 [0.01-0.21]) and maximum (2.4 [2.2] vs 4.2 [2.0]; η2p = 0.11 [0.01-0.24]) pain intensities compared with the control group (mean [SD] age, 62.5 [13.6] years; 5 [17%] women). The intervention group also reported less neuropathic pain (mean [SD], 5.4 [3.4] vs 7.6 [5.1]; η2p = 0.09 [0.004 - 0.22]) and higher quality of life regarding vitality (56.2 [21.5] vs 43.8 [20.9], r = 0.29; 95% CI, 0.01-0.52) and pain (66.8 [27.3] vs 49.5 [27.7], r = 0.31; 95% CI, 0.04-0.54). Patients from the intervention group requested nonopioid analgesics considerably less often (n = 17 [57% ]vs n = 29 [97%]; ϕ = 0.47; 95% CI, 0.30-0.67) associated with a noticeably lower need to escalate pain treatment (n = 3 [10%] vs n = 9 [30%]; mean [SD] ibuprofen dose: 500 [173] mg vs 1133 [650] mg; r = 0.64; 95% CI, 0.02-0.91). No catheter-associated complications were observed. Conclusions and Relevance: Continuous anesthetic wound infusion is associated with reduced postoperative pain and decreased demand for analgesics. It therefore expands the treatment options for postoperative pain in head and neck cancer. Trial Registration: German Clinical Trials Register: DRKS00009378.

Radiation therapy combined with intracerebral convection-enhanced delivery of cisplatin or carboplatin for treatment of the F98 rat glioma.

BACKGROUND: The purpose of this review is to summarize our own experimental studies carried out over a 13-year period of time using the F98 rat glioma as model for high grade gliomas. We evaluated a binary chemo-radiotherapeutic modality that combines either cisplatin (CDDP) or carboplatin, administered intracerebrally (i.c.) by means of convection-enhanced delivery (CED) or osmotic pumps, in combination with either synchrotron or conventional X-irradiation. METHODS: F98 glioma cells were implanted stereotactically into the brains of syngeneic Fischer rats. Approximately 14 days later, either CDDP or carboplatin was administered i.c. by CED, followed 24 h later by radiotherapy using either a synchrotron or, subsequently, megavoltage linear accelerators (LINAC). RESULTS: CDDP was administered at a dose of 3 µg in 5 µL, followed 24 h later with an irradiation dose of 15 Gy or carboplatin at a dose of 20 µg in 10 µL, followed 24 h later with 3 fractions of 8 Gy each, at the source at the European Synchrotron Radiation Facility (ESRF). This resulted in a median survival time (MeST) > 180 days with 33% long term survivors (LTS) for CDDP and a MeST > 60 days with 8 to 22% LTS, for carboplatin. Subsequently it became apparent that comparable survival data could be obtained with megavoltage X-irradiation using a LINAC source. The best survival data were obtained with a dose of 72 µg of carboplatin administered by means of Alzet® osmotic pumps over 7 days. This resulted in a MeST of > 180 days, with 55% LTS. Histopathologic examination of all the brains of the surviving rats revealed no residual tumor cells or evidence of significant radiation related effects. CONCLUSIONS: The results obtained using this combination therapy has, to the best of our knowledge, yielded the most promising survival data ever reported using the F98 glioma model.

Intraluminal infusion of Penta-Galloyl Glucose reduces abdominal aortic aneurysm development in the elastase rat model.

BACKGROUND: An abdominal aortic aneurysm (AAA) is a progressive chronic dilatation of the abdominal aorta with terminally rupture when the aortic wall is so weakened that aortic wall stress exceeds wall strength. No effective medical treatment exists so far. We aimed to test whether intraluminal admission of Penta-Galloyl Glucose (PGG) treatment in a rodent AAA model could hold the potential to inhibit aneurysmal progression. METHOD: Male Sprague Dawley rats had either intraluminal elastase infused for AAA induction or saline to serve as controls. In two independent experimental series, elastase was used to induce AAA followed by an intraluminal PGG (directly or by a drug eluting balloon) treatment. All rats were followed for 28 days and euthanized. In both series, maximal infrarenal aortic diameter was measured at baseline and at termination as a measure of AAA size. In series 2, maximal internally AAA diameter was followed by ultrasound weekly. AAA tissues were analyzed for elastin integrity by millers stain, collagen deposition by masson trichrome staining. In other AAA tissue samples the mRNA level of CD45, lysyloxidase (LOX), lysyloxidase like protein 1 (LOXL1) were determined by qPCR. RESULTS: Direct administration of PGG significantly reduced AAA expansion when compared to controls. PGG treatment resulted in a higher number and more preserved elastic fibers in the aneurysmal wall, while no significant difference was seen in the levels of CD45 and LOX mRNA levels. The drug eluting balloon (DEB) experiment showed no significant difference in AAA size observed neither macroscopically nor ultrasonically. Also the aneurysmal mRNA levels of CD45, LOX and LOXL1 were unchanged between groups. CONCLUSION: A significant reduced expansion of AAAs was observed in the PGG group, suggesting PGG as a drug to inhibit aneurysmal progression, while administration through a DEB did not show a promising new way of administration.

Effectiveness of wound infusion of 0.2% ropivacaine by patient control analgesia pump after minithoracotomy aortic valve replacement: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Local anesthetic wound infusion has become an invaluable technique in multimodal analgesia. The effectiveness of wound infusion of 0.2% ropivacaine delivered by patient controlled analgesia (PCA) pump has not been evaluated in minimally invasive cardiac surgery. We tested the hypothesis that 0.2% ropivacaine wound infusion by PCA pump reduces the cumulative dose of opioid needed in the first 48 h after minithoracothomy aortic valve replacement (AVR). METHODS: In this prospective, randomized, double-blind, placebo-controlled study, 70 adult patients (31 female and 39 male) were analyzed. Patients were randomized to receive 0.2% ropivacaine or 0.9% saline wound infusion by PCA pump for 48 h postoperatively. PCA pump was programmed at 5 ml h- 1 continuously and 5 ml of bolus with 60 min lockout. Pain levels were assessed and recorded hourly by Numeric Rating Scale (NRS). If NRS score was higher than three the patient was administered 3 mg of opioid piritramide repeated and titrated as needed until pain relief was achieved. The primary outcome was the cumulative dose of the opioid piritramide in the first 48 h after surgery. Secondary outcomes were frequency of NRS scores higher than three, patient's satisfaction with pain relief, hospital length of stay, side effects related to the local anesthetic and complications related to the wound catheter. RESULTS: The cumulative dose of the opioid piritramide in the first 48 h after minithoracotomy AVR was significantly lower (p < 0.001) in the ropivacaine (R) group median 3 mg (IQR 6 mg) vs. 9 mg (IQR 9 mg). The number of episodes of pain where NRS score was greater than three median 2 (IQR 2), vs 3 (IQR 3), (p = 0.002) in the first 48 h after surgery were significantly lower in the ropivacaine group, compared to control. Patient satisfaction with pain relief in our study was high. There were no wound infections and no side-effects from the local anesthetic. CONCLUSIONS: Wound infusion of local anesthetic by PCA pump significantly reduced opioid dose needed and improves pain control postoperatively. We have also shown that it is a feasible method of analgesia and it should be considered in the multimodal pain control strategy following minimally invasive cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT03079830 , date of registration: March 15, 2017. Retrospecitvely registered.

Pressure-enabled delivery of gemcitabine in an orthotopic pancreatic cancer mouse model.

BACKGROUND: We describe the use of pancreatic retrograde venous infusion in an orthotopic murine model of pancreatic ductal adenocarcinoma and hypothesize that pancreatic retrograde venous infusion delivery of gemcitabine will increase concentrations of gemcitabine in the tumor and the subsequent tumor response to treatment. METHODS: Murine pancreatic ductal adenocarcinoma (KPC4580P) was transplanted onto the pancreatic tail of C57BL/6J mice. Groups (n = 15) of mice were assigned to sham laparotomy and 100 mg/kg intraperitoneal infusion of gemcitabine (systemic gemcitabine), pancreatic venous isolation with pancreatic retrograde venous infusion of 100 mg/kg gemcitabine, or pancreatic retrograde venous infusion with saline infusion. Tumor pressures were recorded during pancreatic retrograde venous infusion. Mice were killed at 1 hour or 7 days after infusion. RESULTS: Baseline tumor pressures were 45 ± 8 mm Hg, and pancreatic retrograde venous infusion increased tumor pressures by 29 ± 6 mm Hg (P < .01). Pancreatic retrograde venous infusion gemcitabine mice had greater tumor gemcitabine concentrations compared with systemic gemcitabine (127 vs 19 ng/mg; P < .01) and lesser tumor volumes compared with both systemic gem and pancreatic retrograde venous infusion with saline (274 vs 857 vs 629 mm3; P < .01). CONCLUSION: Pancreatic retrograde venous infusion increased tumor pressures greater than baseline, improved gemcitabine delivery, and increased the treatment response. These findings suggest that pressurized, regional delivery overcomes the increased pressure barrier in pancreatic ductal adenocarcinoma. Additional preclinical studies with cytotoxic and immunotherapeutic agents and clinical trials using pressure-enabled drug delivery with pancreatic retrograde venous infusion devices are underway.

Effects of intramammary infusion of Bifidobacterium breve on mastitis pathogens and somatic cell response in quarters from dairy cows with chronic subclinical mastitis.

The present study assessed the effects of intramammary infusion of Bifidobacterium breve (B. breve) on mastitis-causing pathogens and on the somatic cell counts (SCC) in lactating cows with chronic subclinical mastitis. The bacteriological cure rates of 42 quarters from 42 cows infected with Staphylococcus aureus, Corynebacterium bovis, coagulase-negative staphylococci, and environmental streptococci were 18.2% (2/11), 14.3% (1/7), 58.8% (10/17), and 28.6% (2/7), respectively, on day 14 after B. breve infusion. In a second trial, B. breve was infused into 18 quarters from 18 cows with chronic subclinical mastitis from which pathogens had not been isolated; the rates of quarters showing SCC > 50 × 104 cells/ml prior to B. breve infusion that decreased to < 30 × 104 cells/ml after infusion were significantly (p < .01) increased to 61.1% (11/18) on day 14 compared to that prior to infusion (0/18). The intramammary infusion of B. breve appears to be a non-antibiotic approach for elimination of minor pathogens and decreasing SCC in quarters with chronic subclinical mastitis in dairy cows.

Systematic review: medical therapy for fibrostenosing Crohn's disease.

BACKGROUND: Medical therapy and/or endoscopic balloon dilation with intralesional therapies are options for the treatment of small bowel fibrostenotic Crohn's disease (CD). AIM: To perform a systematic review summarising evidence for efficacy of systemic and endoscopic intralesional medical therapy in established small bowel strictures in adult CD patients. METHODS: A systematic search of MEDLINE, EMBASE, CENTRAL and Scopus was conducted. Primary outcomes were rates of surgical resection and repeat endoscopic dilation. Pooled event rates from random effects models across studies with 95% confidence intervals were reported. RESULTS: Ten studies describing systemic medical therapy and eight studies of intralesional injection were included. One randomised controlled trial each for systemic therapy and intrastricture injection were identified. Only observational studies were found for systemic biologic therapies, which exclusively included tumour necrosis factor (TNF) antagonists, while intralesional therapies all involved corticosteroids except for one study that evaluated infliximab. Pooled event rates for surgical resection after systemic and intralesional therapy were 28.3% (95% CI: 18.2%-41.3%) and 18.5% (95% CI: 8.3%-36.2%), respectively over a median follow-up of 23 months (range 5.5-105.8), and 21.8 months (range 5-47). Risk of repeat endoscopic balloon dilation in those with intralesional therapy was 58.3% (95% CI: 36.6%-77.3%) over a median follow-up of 21.8 months (range 5-47). CONCLUSIONS: There are no favoured therapies for patients with stricturing small bowel CD. Data are lacking for ustekinumab and vedolizumab. No endoscopic intralesional medications provided a clear benefit for prevention of repeat EBD or surgery.

Proposed Guidelines for the Management of ESBL in Prosthetic Joint Infections.

The aim of this paper is to establish guidelines for the management of extendedspectrum beta-lactamases (ESBL) associated prosthetic joint infections (PJI). This study reviewed 21 patients in the literature documented with ESBL associated PJI. Literature suggests that patients with ESBL PJI are stratified into either early infections (<3 weeks) or late infections (>3 weeks), for which, appropriate laboratory and imaging studies need to be completed. Favorable outcomes require a two-stage revision with an antibiotic-impregnated spacer and a prolonged course of intravenous carbapenem antibiotic.

Intralesional Triamcinolone for Fistulous Tracts in Hidradenitis Suppurativa: An Uncontrolled Prospective Trial with Clinical and Ultrasonographic Follow-Up.

BACKGROUND: There is little evidence on the use of intralesional triamcinolone (ILT) for managing fistulous tracts in hidradenitis suppurativa (HS). OBJECTIVE: To assess the clinical and ultrasound response to ILT for single fistulous lesions in HS patients. METHODS: A prospective open-label study was conducted to assess response to ILT (40 mg/mL) for fistulous tracts in HS. Consecutive patients (Hurley II stage exclusively) presenting to our department were recruited from August 2016 to August 2018. They received a single injection of ILT as the sole treatment. Lesions were assessed clinically and by ultrasound at baseline and 90 days. RESULTS: Of the 53 included HS patients with fistulous tracts, 36 (67.9%) were women, 30 (56.6%) were smokers, and 36 (67.9%) were obese or overweight (body mass index ≥25). Median Sartorius score was 9.0 (IQR 9.0-36.0), and median duration of the lesion treated was 6 months (IQR 3.0-12.0). Fistulous tracts were injected with 0.5 mL triamcinolone 40 mg/mL. Seven patients were lost to follow-up. At 90 days, 20 (43.5%) lesions showed clinical and ultrasound resolution, 13 (28.3%) showed only clinical resolution while persisting on ultrasound, and 13 (28.3%) persisted both clinically and on ultrasound. Mean clinical size decreased from 17.0 to 5.1 mm (p < 0.0001), while mean length on ultrasound decreased from 16.0 to 8.6 mm (p < 0.0001). LIMITATIONS: Small sample size and no control group. CONCLUSIONS: Our study suggests that ILT is beneficial for small fistulous tracts in HS.

Biological intratumoral therapy for the high-grade glioma part II: vector- and cell-based therapies and radioimmunotherapy.

Management of high-grade gliomas (HGGs) remains a complex challenge with an overall poor prognosis despite aggressive multimodal treatment. New translational research has focused on maximizing tumor cell eradication through improved tumor cell targeting while minimizing collateral systemic side effects. In particular, biological intratumoral therapies have been the focus of novel translational research efforts due to their inherent potential to be both dynamically adaptive and target specific. This two part review will provide an overview of biological intratumoral therapies that have been evaluated in human clinical trials in HGGs, and summarize key advances and remaining challenges in the development of these therapies as a potential new paradigm in the management of HGGs. Part II discusses vector-based therapies, cell-based therapies and radioimmunotherapy.

Biological intratumoral therapy for the high-grade glioma part I: intratumoral delivery and immunotoxins.

Management of high-grade gliomas remains a complex challenge. Standard of care consists of microsurgical resection, chemotherapy and radiation, but despite these aggressive multimodality therapies the overall prognosis remains poor. A major focus of ongoing translational research studies is to develop novel therapeutic strategies that can maximize tumor cell eradication while minimizing collateral side effects. Particularly, biological intratumoral therapies have been the focus of new translational research efforts due to their inherent potential to be both dynamically adaptive and target specific. This two-part review will provide an overview of biological intratumoral therapies and summarize key advances and remaining challenges in intratumoral biological therapies for high-grade glioma. Part I focuses on discussion of the concepts of intratumoral delivery and immunotoxin therapies.

Strong Relationship Between Vascular Function in the Coronary and Brachial Arteries.

Early detection of coronary artery dysfunction is of paramount cardiovascular clinical importance, but a noninvasive assessment is lacking. Indeed, the brachial artery flow-mediated dilation test only weakly correlated with acetylcholine-induced coronary artery function ( r=0.36). However, brachial artery flow-mediated dilation methodologies have, over time, substantially improved. This study sought to determine if updates to this technique have improved the relationship with coronary artery function and the noninvasive indication of coronary artery dysfunction. Coronary artery and brachial artery function were assessed in 28 patients referred for cardiac catheterization (61±11 years). Coronary artery function was determined by the change in artery diameter with a 1.82 µg/min intracoronary acetylcholine infusion. Based on the change in vessel diameter, patients were characterized as having dysfunctional coronary arteries (>5% vasoconstriction) or relatively functional coronary arteries (<5% vasoconstriction). Brachial artery function was determined by flow-mediated dilation, adhering to current guidelines. The acetylcholine-induced change in vessel diameter was smaller in patients with dysfunctional compared with relatively functional coronary arteries (-11.8±4.6% versus 5.8±9.8%, P<0.001). Consistent with this, brachial artery flow-mediated dilation was attenuated in patients with dysfunctional compared with relatively functional coronaries (2.9±1.9% versus 6.2±4.2%, P=0.007). Brachial artery flow-mediated dilation was strongly correlated with the acetylcholine-induced change in coronary artery diameter ( r=0.77, P<0.0001) and was a strong indicator of coronary artery dysfunction (receiver operator characteristic=78%). The current data support that updates to the brachial artery flow-mediated dilation technique have strengthened the relationship with coronary artery function, which may now provide a clinically meaningful indication of coronary artery dysfunction.

Local anaesthetic infiltration via wound catheter versus epidural analgesia in open hepatectomy: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Although epidural analgesia (EA) provides effective pain control after open hepatectomy, postoperative hypotension is a common problem that limits ambulation. There is growing interest in alternative methods of pain control after open abdominal surgery, including a potential role for local anaesthetic infusion via wound catheter (WC). The aim of this study was to evaluate the available evidence for WC in open hepatectomy by conducting a meta-analysis of randomised trials. METHODS: A systematic database search of literature published in the last 20 years was performed. Only randomised controlled trials (RCTs) were included in the study. Meta-analyses were performed using both fixed-effects and random-effects models. RESULTS: WC patients had significantly faster functional recovery (WMD = -0.73 (-1.13, -0.32), I2 = 0%, p = 0.004). There was no significant difference in pain scores on the first postoperative day (POD1). On POD2, WC patients had higher pain scores compared to EA patients (WMD = 0.29 (0.09, 0.49), I2 = 0%, p < 0.004), but this corresponded with significantly lower opioid consumption in WC patients (WMD = -6.29 (-7.92, -4.65), I2 = 62%, p < 0.001). There was no significant difference in major hepatectomy, incision length, complications, length of hospital stay or readmissions between groups. CONCLUSION: Despite higher pain scores on the second postoperative day, functional recovery after open hepatectomy is faster in patients with wound catheters compared with epidural analgesia. Wound catheters should be considered the preferred mode of analgesia after open hepatectomy.