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BackgroundCulturing cells as cell spheres results in a tissue-like environment that drives unique cell phenotypes, making it useful for generating cell populations intended for therapeutic use. Unfortunately, common methods that utilize static suspension culture have limited scalability, making commercialization of such cell therapies challenging. Our team is developing an allogeneic cell therapy for the treatment of lumbar disc degeneration comprised of discogenic cells, which are progenitor cells expanded from human nucleus pulposus cells that are grown in a sphere configuration.MethodsWe evaluate sphere production in Erlenmeyer, horizontal axis wheel, stirred tank bioreactor, and rocking bag format. We then explore the use of ramped agitation profiles and computational fluid dynamics to overcome obstacles related to cell settling and the undesired impact of mechanical forces on cell characteristics. Finally, we grow discogenic cells in stirred tank reactors (STRs) and test outcomes in vitro (potency via aggrecan production and identity) and in vivo (rabbit model of disc degeneration).ResultsComputation fluid dynamics were used to model hydrodynamic conditions in STR systems and develop statistically significant correlations to cell attributes including potency (measured by aggrecan production), cell doublings, cell settling, and sphere size. Subsequent model-based optimization and testing resulted in growth of cells with comparable attributes to the original static process, as measured using both in vitro and in vivo models. Maximum shear rate (1/s) was maintained between scales to demonstrate feasibility in a 50 L STR (200-fold scale-up).ConclusionsTransition of discogenic cell production from static culture to a stirred-tank bioreactor enables cell sphere production in a scalable format. This work shows significant progress towards establishing a large-scale bioprocess methodology for this novel cell therapy that can be used for other, similar cell therapies.

Modern bioprocess development employs statistically optimized design of experiments (DOE) and regression modeling to find optimal bioprocess set points. Using modeling software, such as JMP Pro, it is possible to leverage artificial neural networks (ANNs) to improve model accuracy beyond the capabilities of regression models. Herein, we bridge the gap between a DOE skill set and a machine learning skill set by demonstrating a novel use of DOE to systematically create and evaluate ANN architecture using JMP Pro software. Additionally, we run a mammalian cell culture process at historical, one factor at a time, standard least squares regression, and ANN-derived set points. This case study demonstrates the significant differences between one factor at a time bioprocess development, DOE bioprocess development and the relative power of linear regression versus an ANN-DOE hybrid modeling approach. Supplementary Information The online version contains supplementary material available at 10.1007/s00449-021-02529-3.

Guidance on contact tracing in Chlamydia trachomatis (CT) is limited. CT contacts data over 12 months (1 December 2018–29 November 2019) at a UK sexual health clinic were analysed to determine the appropriateness of the currently recommended six-month ‘look-back’ interval. Age and sex of CT contacts were associated with clinical outcomes. Subgroups of 100 CT positive/negative contacts (each N = 100) were randomly selected. The relationship between time since sexual intercourse with the index case (Last Sexual Intercourse; LSI) and CT positivity was examined; suitability of varying look-back intervals was explored. Of 891 CT contacts (mean age = 25.0 years, 66.2% men), 66.9% tested positive for CT. Positive CT contacts were significantly younger (23.8 ± 6.8 years vs. 27.4 ± 9.1, p < 0.001) and more often women (36.4% vs. 28.5%, p = 0.018) than negative contacts. In the subgroups, the Mann–Whitney U test revealed no significant difference between the LSI of positive and negative contacts ( p = 0.081). 95% of positive CT contacts ( N = 82) were captured within a hypothetical three-month look-back interval. While most CT positive contacts were captured within three months, they appeared to remain proportionately represented beyond this point. Although this supports current guidelines, further research should investigate whether CT contacts involved in longer look-back intervals may require disproportionately greater resources to trace.

We conducted an audit looking at the management of HIV-positive women in the postpartum period. We found that of the women with a previous AIDS-defining condition or a CD4 count 500 cells/µL. A significant finding from our audit was that all of the women who had poor virological control or stopped ART against medical advice had social issues or self-reported depression. The main recommendation was to extend the pregnancy multidisciplinary team (MDT) meeting to include the 12-month postpartum period to offer support to women to try to improve treatment outcomes.

Renal cysts are a common radiological finding in both adults and children. They occur in a variety of conditions, and the clinical presentation, management, and prognosis varies widely. In this article, we discuss the major causes of renal cysts in children and adults with a particular focus on the most common genetic forms. Many cystoproteins have been localized to the cilia centrosome complex (CCC). We consider the evidence for a universal ‘cilia hypothesis’ for cyst formation and the evidence for non-ciliary proteins in cyst formation.

BackgroundIn the UK, Clinical simulation is strongly recommended for training in Medicine. In Genito-urinary Medicine, simulation is used for summative assessment for major examination such as Dip GUM and Dip HIV. Unfortunately it's rarely used for training. New Trainees in GUM have very little experience in Sexual Health. A recent in-house survey showed around 85% would have found simulation useful if included in the induction program and would have addressed training needs specific to the speciality.MethodologyAll new trainees will be invited to participate. Faculty will consist of GUM Consultants and Registrars. The course will consist of 2 parts Skills Workshop Using part-task trainers, candidates will rotate through 5 Stations that will include: -Female Pelvis: for speculum insertion, cervical cytology, Microbiology sampling and bimanual examination -Male Pelvis: for examination and sampling techniques -Rectal examination: for proctoscopy and prostate examination -Anatomy of Male and female genital tract using illustrations -Illustrations of Common Dermatological conditions and skin infections and cryotherapy for warts. Scenario-based Simulation: Trainees will participate in simulated communication scenarios.Objectives: 1. To demonstrate good listening skills2. To use simple, clear language when communication with patients3. To develop understanding of ethics, law and consent.ResultsWe anticipate that trainees will have more confidence during clinical consultations and in managing challenging cases.ConclusionsBetter understanding of the team dynamics and nature of work in GUM will improve working relationships which will ultimately result in better patient care.

Kalso and colleagues summarise drugs used to manage neuropathic pain.1 However, they should have mentioned the potential misuse of pregabalin and gabapentin, which Spence highlighted last year.2 Reports of gabapentin and pregabalin …

Background/introduction The early recognition and investigation of outbreaks of sexually transmitted infections (STIs) is vital for preventing onward transmission. Aim(s)/objectives We sought to understand the facilitators and barriers to outbreak recognition in order to improve early detection. To review the recognition and management of a series of recent outbreaks of sexually transmitted infections in the United Kingdom (UK). To formulate guidance that will enable early recognition of outbreaks. Methods We interviewed clinicians and public health professionals who had been recently involved in identifying and managing STI outbreaks in the UK. Interviews were audio-recorded and transcribed verbatim. Transcripts were analysed using thematic analysis. Results Ten STI outbreaks were reviewed, generally by interviewing both a clinician and public health professional. Health advisers and sexual health consultants often noticed increases in cases with smaller clinics often identifying outbreaks more quickly than larger centres through “soft” signals such as increased partner notification, contacts named multiple times or cases with similar geographical location. Sometimes changing demographics first alerted staff. In two centres, increased ceftriaxone use prompted data review. Public Health England (PHE) regional teams identified two outbreaks: one through analysis of the national dataset (GUMCAD); and one via the formal Infectious Diseases Notifications process. Discussion/conclusion “Soft” signals, picked up in smaller clinics were less readily noticed in larger services. Although quarterly retrospective collation of electronic data by PHE currently limits their role, electronic records should be better exploited locally within services.

Background/introduction When outbreaks of sexually transmitted infections (STIs) are identified, effective management in a timely manner is essential for bringing the outbreak under control. Challenges to achieving this may vary, needing different approaches. Aim(s)/objectives To review the management of outbreaks contrasting by setting and sexual orientation in order to inform responsive guidance. Methods We interviewed clinicians and public health professionals who had recently been involved in identifying and managing STI outbreaks in the United Kingdom. Transcripts were analysed using thematic analysis. Results Ten outbreaks were reviewed. The combination of public health teams’ wider outbreak expertise and clinic staff’s knowledge of the local population was essential when developing management strategies. Partner notification, mainly by health advisers, was very achievable in smaller heterosexual outbreaks but proved challenging in MSM focussed outbreaks where use of mobile apps or anonymous sex was common. Publicity campaigns via social media platforms and third sector organisations were employed although quantifying their impact was difficult. Education of local physicians resulted in syphilis referrals to sexual health services via ophthalmology, gastroenterology, oral and maxillofacial surgery and general practice. Enhanced surveillance enabled venue identification but was time consuming for clinic staff. In gonorrhoea outbreaks, the use of dual NAAT testing as part of the chlamydia screening programme enabled case finding. Discussion/conclusion Traditional management strategies remain important but as the use of social media increases, novel strategies for managing outbreaks are needed. Education of other professionals is essential to maximise case finding.