Fibrin matrices enhance the transplant and efficacy of cytotoxic stem cell therapy for post-surgical cancer

Tumor-homing cytotoxic stem cell (SC) therapy is a promising new approach for treating the incurable brain cancer glioblastoma (GBM). However, problems of retaining cytotoxic SCs within the post-surgical GBM resection cavity are likely to significantly limit the clinical utility of this strategy. Here, we describe a new fibrin-based transplant approach capable of increasing cytotoxic SC retention and persistence within the resection cavity, yet remaining permissive to tumoritropic migration. This fibrin-based transplant can effectively treat both solid and post-surgical human GBM in mice. Using our murine model of image-guided model of GBM resection, we discovered that suspending human mesenchymal stem cells (hMSCS) in a fibrin matrix increased initial retention in the surgical resection cavity 2-fold and prolonged persistence in the cavity 3-fold compared to conventional delivery strategies. Time-lapse motion analysis revealed that cytotoxic hMSCs in the fibrin matrix remain tumoritropic, rapidly migrating from the fibrin matrix to co-localize with cultured human GBM cells. We encapsulated hMSCs releasing the cytotoxic agent TRAIL (hMSC-sTR) in fibrin, and found hMSC-sTR/fibrin therapy reduced the viability of multiple 3-D human GBM spheroids and regressed established human GBM xenografts 3-fold in 11 days. Mimicking clinical therapy of surgically resected GBM, intra-cavity seeding of therapeutic hMSC-sTR encapsulated in fibrin reduced post-surgical GBM volumes 6-fold, increased time to recurrence 4-fold, and prolonged median survival from 15 to 36 days compared to control-treated animals. Fibrin-based SC therapy could represent a clinically compatible, viable treatment to suppress recurrence of post-surgical GBM and other lethal cancer types

Transcranial Doppler monitoring during laparoscopic anterior lumbar interbody fusion

We studied the consequences on cerebral hemodynamics of lengthy laparoscopic procedures requiring pneumoperitoneum and head-down positioning. From October 1995 to April 1999, 17 ASA status I or II patients (16 women and 1 man; mean age, 38 yr) were treated with laparoscopic anterior lumbar fusion. Besides standard perioperative monitoring for laparoscopic surgery, the mean blood-flow velocity of both middle cerebral arteries and the pulsatility index were determined by transcranial Doppler ultrasound. Adequate acoustic windows were encountered in 11 of the 17 patients, and the remaining 6 were excluded from the analysis. PaCO(2) and end-tidal CO(2) were maintained within normal limits (<40 mm Hg); ventilation was optimized in all cases. There was a significant increase (P < 0.05) in heart rate and central venous pressure with the change from supine to head-down position in all patients. Transcranial Doppler results for mean middle cerebral artery blood-flow velocity and pulsatility index showed no significant variations at any of the four time points studied during the procedure. There were no technique-related complications, except for moderate postoperative headache in eight patients that resolved with rest and oxygen therapy. We conclude that lengthy laparoscopic procedures in the head-down position performed in otherwise healthy patients do not significantly affect intracranial circulation

Cardiac tamponade associated with a peripheral vein central venous catheter

We present a case of cardiac tamponade associated with placement of a central venous catheter (CVC) via a peripheral vein in a 14-year-old girl with idiopathic scoliosis undergoing corrective surgery. A number of complications have been described in association with CVC misplacement. Sporadic cases of cardiac tamponade from this have been reported, but the actual incidence is unknown. Death from cardiac tamponade attributed to CVCs ranges from 65 to 100%. In our patient, cannulation of the pericardiophrenic vein was probably the cause of cardiac tamponade, based on radiological evidence that the initial location of the catheter was near the right atrium and possibly at the outlet of the pericardiophrenic vein. The catheter could have advanced into the vein and then to the pericardial sac with postural changes. The acute clinical course of cardiac tamponade in our patient had potentially lethal hemodynamic repercussions. The main diagnostic test for this condition is echocardiography and the only effective treatment is drainage of the pericardial effusion. Echocardiography should be performed before pericardiocentesis except in life-threatening situations or high clinical suspicion. Although they are rare, it is important to be aware of the potential for CVC complications

Electrospun nanofibrous scaffolds increase the efficacy of stem cell-mediated therapy of surgically resected glioblastoma

Engineered stem cell (SC)-based therapy holds enormous promise for treating the incurable brain cancer glioblastoma (GBM). Retaining the cytotoxic SCs in the surgical cavity after GBM resection is one of the greatest challenges to this approach. Here, we describe a biocompatible electrospun nanofibrous scaffold (bENS) implant capable of delivering and retaining tumor-homing cytotoxic stem cells that suppress recurrence of post-surgical GBM. As a new approach to GBM therapy, we created poly(l-lactic acid) (PLA) bENS bearing drug-releasing human mesenchymal stem cells (hMSCs). We discovered that bENS-based implant increased hMSC retention in the surgical cavity 5-fold and prolonged persistence 3-fold compared to standard direct injection using our mouse model of GBM surgical resection/recurrence. Time-lapse imaging showed cytotoxic hMSC/bENS treatment killed co-cultured human GBM cells, and allowed hMSCs to rapidly migrate off the scaffolds as they homed to GBMs. In vivo, bENS loaded with hMSCs releasing the anti-tumor protein TRAIL (bENSsTR) reduced the volume of established GBM xenografts 3-fold. Mimicking clinical GBM patient therapy, lining the post-operative GBM surgical cavity with bENSsTR implants inhibited the re-growth of residual GBM foci 2.3-fold and prolonged post-surgical median survival from 13.5 to 31 days in mice. These results suggest that nanofibrous-based SC therapies could be an innovative new approach to improve the outcomes of patients suffering from terminal brain cancer

Travel-associated Rabies in Austrian Man

Rabies developed in an Austrian man after he was bitten by a dog in Agadir, Morocco. Diagnosis was confirmed by reverse transcription–polymerase chain reaction and immunohistochemistry. The patient's girlfriend was bitten by the same dog, but she did not become ill

Thromboprophylaxis in elective spinal surgery: a protocol for systematic review

Background: Venous thromboembolism (VTE) is a serious, sometimes life-threatening complication that can occur following spine surgery. The incidence of VTE, and the optimal type and timing of thromboprophylaxis for this complication in elective spine surgery is a matter of debate. Objective: To perform a systematic review with the aim of clarifying the efficacy and adverse effects of mechanical and chemical prophylaxis for preventing thromboembolic complications in elective spine surgery for conditions other than trauma and malignant disease. Methods/design: A search strategy of related articles up to March 2018 was designed and executed in Medline and Embase. Patients: adolescents (>10 years) and adults undergoing elective surgery for spinal deformity or degenerative disease (from C1 to S1). Intervention: Perioperative mechanical and chemical thromboprophylaxis. Studies could be randomized controlled trials or observational studies that reported data on any relevant clinical outcomes. Results: In total, 2451 uniquecitations were identified and 35 studies were ultimately included in the systematic review. The overall mean incidence of complications was 3.7% for deep venous thrombosis, 0.0% for pulmonary embolism, and 3.7% for bleeding in chemoprophylaxis group; 2.9% for deep venous thrombosis, 0.4% for pulmonary embolism and 0.0% for bleeding in mechanoprophylaxis; and 0.7% for deep venous thrombosis, 0.1% for pulmonary embolism and 0.2% for bleeding in mixed prophylaxis group with no specific data on these rates for the type of patient and type and location of surgery. None of the articles retrieved provided information on the adolescent population. Discussion and conclusions: The poor design and high variability among the studies regarding characteristics of study population, details of interventions, and definitions of outcomes, determines a low quality of the available evidence and limits the interpretation of the results. We were unable to identify a clear advantage of one type of thromboprophylaxis over the other, although there was an increased risk of bleeding with chemoprophylaxis, which could favor the use of mechanoprophylaxis in this scenario