BACKGROUND: Virtual reality is increasingly being utilized by clinicians to facilitate analgesia and anxiolysis within an inpatient setting. There is however, a lack of a clinically relevant review to guide its use for this purpose. OBJECTIVE: To systematically review the current evidence for the efficacy of virtual reality as an analgesic in the management of acute pain and anxiolysis in an inpatient setting. METHODS: A comprehensive search was conducted up to and including January 2019 on PubMed, Ovid Medline, EMBASE, and Cochrane Database of Systematic reviews according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Search terms included virtual reality, vr, and pain. Primary articles with a focus on acute pain in the clinical setting were considered for the review. Primary outcome measures included degree of analgesia afforded by virtual reality therapy, degree of anxiolysis afforded by virtual reality therapy, effect of virtual reality on physiological parameters, side effects precipitated by virtual reality, virtual reality content type, and type of equipment utilized. RESULTS: Eighteen studies were deemed eligible for inclusion in this systematic review; 67% (12/18) of studies demonstrated significant reductions in pain with the utilization of virtual reality; 44% (8/18) of studies assessed the effects of virtual reality on procedural anxiety, with 50% (4/8) of these demonstrating significant reductions; 28% (5/18) of studies screened for side effects with incidence rates of 0.5% to 8%; 39% (7/18) of studies evaluated the effects of virtual reality on autonomic arousal as a biomarker of pain, with 29% (2/7) demonstrating significant changes; 100% (18/18) of studies utilized a head mounted display to deliver virtual reality therapy, with 50% being in active form (participants interacting with the environment) and 50% being in passive form (participants observing the content only). CONCLUSIONS: Available evidence suggests that virtual reality therapy can be applied to facilitate analgesia for acute pain in a variety of inpatient settings. Its effects, however, are likely to vary by patient population and indication. This highlights the need for individualized pilot testing of virtual reality therapy's effects for each specific clinical use case rather than generalizing its use for the broad indication of facilitating analgesia. In addition, virtual reality therapy has the added potential of concurrently providing procedural anxiolysis, thereby improving patient experience and cooperation, while being associated with a low incidence of side effects (nausea, vomiting, eye strain, and dizziness). Furthermore, findings indicated a head mounted display should be utilized to deliver virtual reality therapy in a clinical setting with a slight preference for active over passive virtual reality for analgesia. There, however, appears to be insufficient evidence to substantiate the effect of virtual reality on autonomic arousal, and this should be considered at best to be for investigational uses, at present.

Targeting cell division by chemotherapy is a highly effective strategy to treat a wide range of cancers. However, there are limitations of many standard-of-care chemotherapies: undesirable drug toxicity, side-effects, resistance and high cost. New small molecules which kill a wide range of cancer subtypes, with good therapeutic window in vivo, have the potential to complement the current arsenal of anti-cancer agents and deliver improved safety profiles for cancer patients. We describe results with a new anti-cancer small molecule, WEHI-7326, which causes cell cycle arrest in G2/M, cell death in vitro, and displays efficacious anti-tumor activity in vivo. WEHI-7326 induces cell death in a broad range of cancer cell lines, including taxane-resistant cells, and inhibits growth of human colon, brain, lung, prostate and breast tumors in mice xenografts. Importantly, the compound elicits tumor responses as a single agent in patient-derived xenografts of clinically aggressive, treatment-refractory neuroblastoma, breast, lung and ovarian cancer. In combination with standard-of-care, WEHI-7326 induces a remarkable complete response in a mouse model of high-risk neuroblastoma. WEHI-7326 is mechanistically distinct from known microtubule-targeting agents and blocks cells early in mitosis to inhibit cell division, ultimately leading to apoptotic cell death. The compound is simple to produce and possesses favorable pharmacokinetic and toxicity profiles in rodents. It represents a novel class of anti-cancer therapeutics with excellent potential for further development due to the ease of synthesis, simple formulation, moderate side effects and potent in vivo activity. WEHI-7326 has the potential to complement current frontline anti-cancer drugs and to overcome drug resistance in a wide range of cancers.

<jats:title>Abstract</jats:title><jats:p>Robot-assisted laparoscopy has been developed to overcome some of the important limitations of conventional laparoscopy. In particular, the provision of stable magnified three-dimensional vision, tremor filtering, motion scaling, and articulated instruments with robot-assisted surgery has the potential to enable more surgeons to perform more complex surgery compared with conventional laparoscopy. The aim of this study was to evaluate the utility of a new robot-assisted surgical system (Versius, CMR Surgical, Cambridge, UK) for gynecologic procedures in a preclinical setting. Cadaveric sessions were conducted to evaluate the ability of the system to complete all surgical steps required for a robot-assisted total laparoscopy hysterectomy. A live animal (porcine) model was used to assess the system in performing oviduct removal as a surrogate for robot-assisted total laparoscopy hysterectomy. Procedures were performed by experienced gynecologic surgeons, supported by a surgical team. The precise surgical steps conducted to conclude that the procedures could be fully completed were systematically recorded, as well as instruments used and endoscope angle. In total, six gynecologic procedures were performed in cadavers by four surgeons; 16/17 procedures were completed successfully. Positioning of the ports and bedside units reflected the surgeons’ preferred laparoscopic setup and enabled good surgical access and reach, as exemplified by the high procedure completion rate. Oviduct removal procedures performed in pigs were all completed successfully by a single surgeon. This preclinical study of a new robot-assisted surgical system for gynecologic procedures demonstrated the safety and effectiveness of the system in cadaver and porcine models. Further studies are required to assess its clinical utility.</jats:p>

OBJECTIVE: To determine heart rate centiles during the first 5 min after birth in healthy term newborns delivered vaginally with delayed cord clamping. DESIGN: Single-centre prospective observational study. SETTING: Stavanger University Hospital, Norway, March-August 2019. PATIENTS: Term newborns delivered vaginally were eligible for inclusion. Newborns delivered by vacuum or forceps or who received any medical intervention were excluded. INTERVENTIONS: A novel dry electrode electrocardiography monitor (NeoBeat) was applied to the newborn's chest immediately after birth. The newborns were placed on their mother's chest or abdomen, dried and stimulated, and cord clamping was delayed for at least 1 min. MAIN OUTCOME MEASURES: Heart rate was recorded at 1 s intervals, and the 3rd, 10th, 25th, 50th, 75th, 90th and 97th centiles were calculated from 5 s to 5 min after birth. RESULTS: 898 newborns with a mean (SD) birth weight 3594 (478) g and gestational age 40 (1) weeks were included. The heart rate increased rapidly from median (IQR) 122 (98-146) to 168 (146-185) beats per minute (bpm) during the first 30 s after birth, peaking at 175 (157-189) bpm at 61 s after birth, and thereafter slowly decreasing. The third centile reached 100 bpm at 34 s, suggesting that heart rates <100 bpm during the first minutes after birth are uncommon in healthy newborns after delayed cord clamping. CONCLUSION: This report presents normal heart rate centiles from 5 s to 5 min after birth in healthy term newborns delivered vaginally with delayed cord clamping.

INTRODUCTION: Early identification of infants requiring surfactant therapy improves outcomes. We evaluated the accuracy of delivery room lung ultrasound (LUS) to predict surfactant therapy in very- and extremely preterm infants. METHODS: Infants born at <320/7 weeks were prospectively enrolled at 2 centres. LUS videos of both sides of the chest were obtained 5-10 min, 11-20 min, and 1-3 h after birth. Clinicians were masked to the results of the LUS assessment and surfactant therapy was provided according to local guidelines. LUS videos were graded blinded to clinical data. Presence of unilateral type 1 ('whiteout') LUS or worse was considered test positive. Receiver Operating Characteristic (ROC) analysis compared the accuracy of LUS and an FiO2 threshold of 0.3 to predict subsequent surfactant therapy. RESULTS: Fifty-two infants with a median age of 276/7 weeks (IQR 260/7-286/7) were studied. Thirty infants (58%) received surfactant. Area under the ROC curve (AUC) for LUS at 5-10 min, 11-20 min and 1-3 h was 0.78 (95% CI, 0.66-0.90), 0.76 (95% CI, 0.65-0.88) and 0.86 (95% CI, 0.75-0.97) respectively, outperforming FiO2 at the 5-10 min timepoint (AUC 0.45, 95% CI 0.29-0.62, p = 0.001). At 11-20 min, LUS had a specificity of 95% (95% CI 77-100%) and sensitivity of 59% (95% CI, 39-77%) to predict surfactant therapy. All infants born at 23-276/7 weeks with LUS test positive received surfactant. Twenty-six infants (50%) had worsening of LUS grades on serial assessment. CONCLUSIONS: LUS in the delivery room and accurately predicts surfactant therapy in infants <320/7 weeks.

Naive and memory T cells are maintained in a quiescent state, yet capable of rapid response and differentiation to antigen challenge via molecular mechanisms that are not fully understood. In naive cells, the deletion of Foxo1 following thymic development results in the increased expression of multiple AP-1 family members, rendering T cells less able to respond to antigenic challenge. Similarly, in the absence of FOXO1, post-infection memory T cells exhibit the characteristics of extended activation and senescence. Age-based analysis of human peripheral T cells reveals that levels of FOXO1 and its downstream target, TCF7, are inversely related to host age, whereas the opposite is found for AP-1 factors. These characteristics of aging also correlate with the formation of T cells manifesting features of cellular senescence. Our work illustrates a role for FOXO1 in the active maintenance of stem-like properties in T cells at the timescales of acute infection and organismal life span.

Although relatively uncommon, the incidence of fetal echogenic lung lesions - a heterogeneous group of anomalies that includes congenital pulmonary airway malformations (CPAM) and bronchopulmonary sequestrations (BPS) - has increased recently. Two decades ago, the CPAM-volume ratio (CVR) was first described as a tool to predict the development of hydrops, with this outcome found to be unlikely in fetuses with CVRs of ≤1.6 cm2. Since then, no clear international consensus has evolved as to the optimal CVR thresholds for the prediction of fetal/neonatal outcomes. This systematic review aimed to assess all original research studies that reported on the predictive utility of the CVR. Potentially relevant papers were identified through searching for citations of the paper that originally described the CVR, in addition to keyword searches of electronic databases. Fifty-two original research papers were included in the final review. Of these, 34 used the CVR for descriptive purposes only, 5 assessed the validity of established thresholds in different populations, and 13 proposed new thresholds. The evidence identified in this review would suggest that a threshold much lower than 1.6 cm2 is likely to be of greater utility in most populations for many outcomes of perinatal relevance. For neonatal outcomes (mostly respiratory compromise at birth), a CVR on the initial ultrasound scan ranging from 0.5 to 1.0 cm2 appears to have the greatest predictive value. Although a number of studies concurred that 1.6 cm2 was a useful threshold for the prediction of hydrops, many others were unable to assess this due to the rarity of this complication. For this reason, thresholds as low as 0.4 cm2 may be more useful for the prediction of a broader range of fetal concerns, including mediastinal shift and fluid collections. Further large-scale studies are required to determine the true utility of this well-established index.

OBJECTIVE: To identify attention profiles at 7 and 13 years, and transitions in attention profiles over time in children born very preterm (VP; <30 weeks' gestation) and full term (FT), and examine predictors of attention profiles and transitions. METHODS: Participants were 167 VP and 60 FT children, evaluated on profiles across five attention domains (selective, shifting and divided attention, processing speed, and behavioral attention) at 7 and 13 years using latent profile analyses. Transitions in profiles were assessed with contingency tables. For VP children, biological and social risk factors were tested as predictors with a multinomial logistic regression. RESULTS: At 7 and 13 years, three distinct profiles of attentional functioning were identified. VP children were 2-3 times more likely to show poorer attention profiles compared with FT children. Transition patterns between 7 and 13 years were stable average, stable low, improving, and declining attention. VP children were two times less likely to have a stable average attention pattern and three times more likely to have stable low or improving attention patterns compared with FT children. Groups did not differ in declining attention patterns. For VP children, brain abnormalities on neonatal MRI and greater social risk at 7 years predicted stable low or changing attention patterns over time. CONCLUSIONS: VP children show greater variability in attention profiles and transition patterns than FT children, with almost half of the VP children showing adverse attention patterns over time. Early brain pathology and social environment are markers for attentional functioning.

Cell therapies for neonatal morbidities are progressing to early phase clinical trials. However, protocols for intravenous (IV) delivery of cell therapies to infants have not been evaluated. It has been assumed the cell dose prescribed is the dose delivered. Early in our clinical trial of human amnion epithelial cells (hAECs), we observed cells settling in the syringe and IV tubing used to deliver the suspension. The effect on dose delivery was unknown. We aimed to quantify this observation and determine an optimal protocol for IV delivery of hAECs to extremely preterm infants. A standard pediatric infusion protocol was modeled in the laboratory. A syringe pump delivered the hAEC suspension over 60 minutes via a pediatric blood transfusion set (200-μm filter and 2.2 mL IV line). The infusion protocol was varied by agitation methods, IV-line volumes (0.2-2.2 mL), albumin concentrations (2% vs 4%), and syringe orientations (horizontal vs vertical) to assess whether these variables influenced the dose delivered. The influence of flow rate (3-15 mL/h) was assessed after other variables were optimized. The standard infusion protocol delivered 17.6% ± 9% of the intended hAEC dose. Increasing albumin concentration to 4%, positioning the syringe and IV line vertically, and decreasing IV-line volume to 0.6 mL delivered 99.7% ± 13% of the intended hAEC dose. Flow rate did not affect dose delivery. Cell therapy infusion protocols must be considered. We describe the refinement of a cell infusion protocol that delivers intended cell doses and could form the basis of future neonatal cell delivery protocols.

BACKGROUND: The association between smoking, diabetes and obesity and oncological outcomes in patients with stage III colon cancer treated with surgery and adjuvant chemotherapy is unclear. AIM: To evaluate whether smoking, obesity and diabetes are associated with the disease-free survival and overall survival rates of patients with stage III colon cancer who have received adjuvant chemotherapy. METHODS: Patients were selected from the prospectively maintained Australian Cancer Outcomes and Research Database (ACCORD). All stage III colon cancer patients who received adjuvant chemotherapy between January 2003 to December 2015 were retrospectively analyzed. The three primary exposures of interest were smoking status, body mass index (BMI) and diabetic (DM) status. The primary outcomes of interest were disease-free survival (DFS) and overall survival (OS). RESULTS: A total of 785 patients between 2003 and 2015 were included for analysis. Using Kaplan-Meier survivorship curves, there was no association between OS and smoking (P = .71), BMI (P = .3) or DM (P = .72). Similarly, DFS did not reveal an association with smoking (P = .34), BMI (P = .2) and DM (P = .34). Controlling for other covariates the results did not reach statistical significance in adjusted multiple regression models. CONCLUSION: Smoking, obesity and DM were not shown to influence DFS or OS for patients with stage III colon cancer who have received adjuvant chemotherapy.