Simulating traumatic brain injury in vitro:developing high throughput models to test biomaterial based therapies

Traumatic brain injuries are serious clinical incidents associated with some of the poorest outcomes in neurological practice.Coupled with the limited regenerative capacity of the brain,this has significant implications for patients,carers,and healthcare systems,and the requirement for life-long care in some cases.Clinical treatment currently focuses on limiting the initial neural damage with longterm care/support from multidisciplinary teams.Therapies targeting neuroprotection and neural regeneration are not currently available but are the focus of intensive research.Biomaterial-based interventions are gaining popularity for a range of applications including biomolecule and drug delive ry,and to function as cellular scaffolds.Experimental investigations into the development of such novel therapeutics for traumatic brain injury will be critically underpinned by the availability of appropriate high thro ughput,facile,ethically viable,and pathomimetic biological model systems.This represents a significant challenge for researchers given the pathological complexity of traumatic brain injury.Specifically,there is a concerted post-injury response mounted by multiple neural cell types which includes microglial activation and astroglial scarring with the expression of a range of growth inhibito ry molecules and cytokines in the lesion environment.Here,we review common models used for the study of traumatic brain injury(ranging from live animal models to in vitro systems),focusing on penetrating traumatic brain injury models.We discuss their relative advantages and drawbacks for the developmental testing of biomaterial-based therapies.

Radiofrequency ablation for early oesophageal squamous neoplasia:Outcomes form United Kingdom registry

AIM:To report outcomes on patients undergoing radiofrequency ablation(RFA)for early oesophageal squamous neoplasia from a National Registry.METHODS:A Prospective cohort study from 8 tertiary referral centres in the United Kingdom.Patients with squamous high grade dysplasia(HGD)and early squamous cell carcinoma(ESCC)confined to the mucosa were treated.Visible lesions were removed by endoscopic mucosal resection(EMR)before RFA.Following initial RFA treatment,patients were followed up 3monthly.Residual flat dysplasia was treated with RFA until complete reversal dysplasia(CR-D)was achieved or progression to invasive Squamous cell cancer defined as infiltration into the submucosa layer or beyond.The main outcome measures were CR-D at 12 mo from start of treatment,long term durability,progression to cancer and adverse events.RESULTS:Twenty patients with squamous HGD/ESCC completed treatment protocol.Five patients(25%)had EMR before starting RFA treatment.CR-D was 50%at12 mo with a median of 1 RFA treatment,mean 1.5(range 1-3).Two further patients achieved CR-D with repeat RFA after this time.Eighty per cent with CR-D remain dysplasia free at latest biopsy,with median follow up 24 mo(IQR 17-54).Six of 20 patients(30%)progressed to invasive cancer at 1 year.Four patients(20%)required endoscopic dilatations for symptomatic structuring after treatment.Two of these patients have required serial dilatations thereafter for symptomatic dysphagia with a median of 4 dilatations per patient.The other 2 patients required only a single dilatation to achieve an adequate symptomatic response.One patient developed cancer during follow up after end of treatment protocol.CONCLUSION:The role of RFA in these patients re-mains unclear.In our series 50%patients responded at12 mo.These figures are lower than limited published data.

Situs inversus abdominus and malrotation in an adult with Ladd's band formation leading to intestinal ischaemia

Situs inversus abdominus with rotational anomaly of the intestines is an extremely rare condition. Although intestinal malrotation has been recognized as a cause of obstruction in infants and children and may be complicated by intestinal ischaemia, it is very rare in adults. When it occurs in the adult patient, it may present acutely as bowel obstruction or intestinal ischaemia or chronically as vague intermittent abdominal pain. Herein, we present an acute presentation of a case of situs inversus abdominus and intestinal malrotation with Ladd＇s band leading to infarction of the intestine in a 32 year old woman.

Are “Straight to Test” Pathways Always Best for Patients? A Prospective Observational Study of Two-Week-Wait Colorectal Referrals

Aim: Many centres have adopted a straight to test approach to deliver a fast-track service for suspected lower GI cancer. We undertook a prospective comparison between patients having a straight to test (STT) flexible sigmoidoscopy and those attending an outpatient appointment (OPA). The study aimed to determine whether STT reduced diagnostic time without additional investigations. Methods: An observational study of 200 consecutive fast-track colorectal referrals was undertaken. Data collected included: patient demographics, whether STT or OPA, investigations undertaken (including dates) and final diagnosis. Outcomes were compared by adjusted linear regression and logistic regression, for numerical and binary outcomes respectively. Potential confounding factors included were: age, gender and whether NICE referral criteria were achieved. Results: 186 out of 200 referrals attended their appointment, 62% (116/186) went STT and 38% (70/186) had an OPA. No significant difference was seen in the number of days to final investigation, adjusted coefficient -3.71, 95% C.I. -8.92 to 1.50. The STT group had 0.4 more tests per patient, adjusted 95% C.I. 0.07 to 0.73, than the OPA group. Significantly more patients in the STT group had a flexible sigmoidoscopy in addition to whole colonic imaging (all modalities), compared to the OPA group, adjusted OR of 93.47 (95% C.I. 29.26 to 298.54). Conclusion: This study highlights the potential disadvantages of STT flexible sigmoidoscopy for patients referred under the two-week-rule with suspected lower GI cancer. Despite the previously published work highlighting the potential cost and time benefits, it may come at the sacrifice of exposing patients to additional investigations.

HeartSmart^(TM):A New Method of Assessing Hydration in Neurosurgical Patients

Background: Maintenance of normal fluid homeostasis is challenging in neurosurgical patients. Consequently, we studied hydration assessment in neurosurgical intensive care patients. Methods: Pulmonary artery catheter thermodilution (PACTD) is the conventional method for measuring cardiac index (CI) and mean pulmonary artery occlusion (MPAOP) or wedge pressure (MPWP). We compared values from this technique with those derived from continuous cardiac dynamic monitoring (CCDM)-HeartSmart?, a new, less invasive, software-based technique. Over 4 years, we undertook an audit of 101 paired sets of data from 21 patients with sub-arachnoid hemorrhage who had pulmonary artery flotation catheters inserted as part of their treatment. Measured values of CI and MPWP were obtained retrospectively from patients’ charts and compared with values calculated using CCDM-HeartSmart? software. Results: Using the Bland-Altman method for comparing two measurement techniques, there was good agreement between measured and calculated MPWP (mean of differences –1.81, SD 3.97, SE 0.39, 95% CI –2.59 to 2.04 l/min/m2;two-sided p 2). This indicates that, when estimating CI and MPWP in critically ill neurosurgical patients, CCDM-HeartSmart? provides values close to those generated using PACTD. Conclusions: The CCDM-HeartSmart? could prove invaluable for optimizing response to fluid replacement and for guiding cardiovascular support in neurosurgical patients. This new, simple technology may help to facilitate routine adoption of perioperative optimization of blood flow using early goal-directed therapy.

Validating HeartSmart^(■) against the Cardiopulmonary Bypass Machine

Purpose: To assess the utility of HeartSmart?, a new method that uses empirical physiological formulae to estimate hemodynamic variables, in estimating cardiac index during open heart surgery when compared with the cardiopulmonary bypass machine. Methods: This was a prospective, blinded study of patients undergoing elective cardiac bypass surgery. We monitored and compared the flow rates provided by the cardiopulmonary bypass machine (roller pump) with estimates derived from the empirical physiological formulae embedded in the HeartSmart? monitor in 32 patients. Cardiac index values were compared at the start of cardiopulmonary bypass, during re-warming, and at the end of cardiopulmonary bypass. Results: A total of 256 paired sets of measurements were suitable for comparison. The mean of the differences or bias (95% limits of agreement) was 0.09 l/min/m2 and the limits of agreement –0.86 to 1.05 l/min/m2. The mean difference of the sets of 256 measurements was 585.5 l/min/m for the pump and 575.0 l/min/m2 for the empirical physiological formulae—a difference of 5% l/min/m2. The range of flow rates for the pump was 1.2 to 2.85 l/min/m2;for the empirical physiological formulae, the range was 1.2 to 3.0 l/min/m2. Conclusion: The cardiac index estimates derived from the empirical physiological formulae in the HeartSmart? software are in good agreement with pump cardiac output rates. These results suggest that HeartSmart? measurements are sufficiently accurate for assessing hemodynamic variables in many groups of patients.

The diagnostic conundrum in necrotizing otitis externa

Necrotizing otitis externa(NOE)is an aggressive and fast‐evolving infection of the external auditory canal.Late diagnoses and untreated cases can lead to severe,even fatal consequences and so early diagnosis and treatment are paramount.NOE is a notoriously challenging diagnosis to make.It is therefore important to understand what diagnostic modalities are available and how otolaryngologists can use them to accurately treat such an aggressive disease.This review aims to evaluate the different diagnostic options available in NOE and discuss their advantages and limitations,thus,providing an up‐to‐date picture of the multimodal approach required in the diagnosis of this disease.

Using no-cost mobile phone reminders to improve attendance for HIV test results: a pilot study in rural Swaziland

Background:Mobile technology has great potential to improve adherence and treatment outcomes in healthcare settings.However,text messaging and phone calls are unaffordable in many resource-limited areas.This study investigates the use of a no-cost alternative mobile phone technology using missed calls(‘buzzing’)to act as a patient reminder.The use of missed calls as a patient reminder was evaluated for feasibility and effectiveness as an appointment reminder in the follow-up of newly-diagnosed human immunodeficiency virus(HIV)positive patients in an HIV testing and counselling department in rural Swaziland.Methods:This pilot study uses a before-and-after operational research study design,with all patients with mobile phones being offered the intervention.The primary outcome was the rate of attendance at the HIV testing and counselling department for collection of results in those with mobile phones before and after the introduction of the intervention.Results:Over two-thirds,71.8%(459/639),of patients had a mobile phone.All patients with a mobile phone consented to being buzzed.There was no difference in attendance for follow-up at the clinic before and after the intervention was implemented(80.1%versus 83.3%,p=0.401),or after adjusting for confounding factors(OR 1.13,p=0.662).Conclusion:This pilot study illustrates that mobile technology may be feasible in rural,resource-poor settings as there are high rates of mobile phone ownership and the intervention had a 100%uptake rate,with positive feedback from staff and patients.In this particular setting,the intervention did not improve attendance rates.However,further research is planned to investigate the impact on adherence to appointments and medications in other settings,such as HIV chronic care follow-up and as part of an enhanced package to improve adherence.

Effects of financial incentives for treatment supporters on tuberculosis treatment outcomes in Swaziland: a pragmatic interventional study

Background:Swaziland has the highest national incidence of tuberculosis(TB)in the world,with treatment success rates well below the 85%international target.Treatment support as part of comprehensive TB services is a core component of the Stop TB Strategy.This study investigated the effects of financial incentives for treatment supporters on TB treatment outcomes in Swaziland.Methods:This was a controlled study that compared treatment outcomes for patients with a treatment supporter who received or did not receive a financial incentive.Results:The intervention group had a higher chance of treatment success as compared with the control group:73%(95%confidence intervals[CIs]66–80%)versus 60%(95%CIs 57–64%),respectively,p=0.003.This improvement remained significant when treatment success rates were adjusted for differences in baseline characteristics,with the effect of incentivised treatment supporters on treatment outcomes having an odds ratio(OR)of 1.8.There was also a significant improvement in the death rate in the intervention group,as compared with the control group(10.6 versus 23.5%,p=<0.001).Conclusion:Incentives provided to TB treatment supporters appear to significantly improve TB treatment outcomes.Incentivising treatment support may be appropriate as an effective addition to support and supervision measures(199 words).