Function Follows Form: Oriented Substrate Nanotopography Overrides Neurite-Repulsive Schwann Cell-Astrocyte Barrier Formation in an In Vitro Model of Glial Scarring.

Schwann cell (SC) transplantation represents a promising therapeutic approach for traumatic spinal cord injury but is frustrated by barrier formation, preventing cell migration, and axonal regeneration at the interface between grafted SCs and reactive resident astrocytes (ACs). Although regenerating axons successfully extend into SC grafts, only a few cross the SC-AC interface to re-enter lesioned neuropil. To date, research has focused on identifying and modifying the molecular mechanisms underlying such scarring cell-cell interactions, while the influence of substrate topography remains largely unexplored. Using a recently modified cell confrontation assay to model SC-AC barrier formation in vitro, highly oriented poly(ε-caprolactone) nanofibers were observed to reduce AC reactivity, induce extensive oriented intermingling between SCs and ACs, and ultimately enable substantial neurite outgrowth from the SC compartment into the AC territory. It is anticipated that these findings will have important implications for the future design of biomaterial-based scaffolds for nervous tissue repair.

Characterization of a Novel Aspect of Tissue Scarring Following Experimental Spinal Cord Injury and the Implantation of Bioengineered Type-I Collagen Scaffolds in the Adult Rat: Involvement of Perineurial-like Cells?

Numerous intervention strategies have been developed to promote functional tissue repair following experimental spinal cord injury (SCI), including the bridging of lesion-induced cystic cavities with bioengineered scaffolds. Integration between such implanted scaffolds and the lesioned host spinal cord is critical for supporting regenerative growth, but only moderate-to-low degrees of success have been reported. Light and electron microscopy were employed to better characterise the fibroadhesive scarring process taking place after implantation of a longitudinally microstructured type-I collagen scaffold into unilateral mid-cervical resection injuries of the adult rat spinal cord. At long survival times (10 weeks post-surgery), sheets of tightly packed cells (of uniform morphology) could be seen lining the inner surface of the repaired dura mater of lesion-only control animals, as well as forming a barrier along the implant-host interface of the scaffold-implanted animals. The highly uniform ultrastructural features of these scarring cells and their anatomical continuity with the local, reactive spinal nerve roots strongly suggest their identity to be perineurial-like cells. This novel aspect of the cellular composition of reactive spinal cord tissue highlights the increasingly complex nature of fibroadhesive scarring involved in traumatic injury, and particularly in response to the implantation of bioengineered collagen scaffolds.

Study To Evaluate the Performance of a Point-of-Care Whole-Blood HIV Viral Load Test (SAMBA II HIV-1 Semi-Q Whole Blood).

Remote areas of many low and middle income (LMI) countries have poor access to HIV viral load (HIV VL) testing. The SAMBA II (simple amplification-based assay) Semi-Q whole-blood test (Diagnostics for the Real World [DRW], Cambridge, UK) is a point-of-care assay, which uses leucodepletion technology to allow whole-blood testing in remote settings. A total of 1,540 consecutive HIV-positive clinic patients in Cameroon (250), United Kingdom (633), Ukraine (412), and Zimbabwe (245) donated venous blood (all countries) and finger prick blood (all except UK) for testing on SAMBA II. SAMBA II results were compared with simultaneous plasma results on the Abbott RealTime HIV-1 (Abbott Molecular, Des Plaines, IL) viral load assay and interpreted as either <1,000 RNA copies/ml or ≥1,000 RNA copies/ml. For 1,528 venous whole-blood samples tested on SAMBA II, overall percent agreement with the reference test at a cutoff HIV VL of ≥1,000 copies/ml was 96.9% (1,480/1,528; 95% confidence interval [CI], 95.9% to 97.7%), negative percent agreement was 97.7% (1,259/1,289; 95% CI, 96.7% to 98.4%), and positive percent agreement was 92.5% (221/239; 95% CI, 88.4% to 95.5%). For 854 finger prick samples, there was 95.0% (811/854; 95% CI, 93.3% to 96.3%) overall percent agreement, 98.0% (625/638; 95% CI, 96.5% to 98.9%) negative percent agreement, and 86.1% (186/216; 95% CI, 80.8% to 90.4%) positive percent agreement. These rose to 93.5% (82.1% to 98.6%), 97.6% (95.6% to 98.8%), and 95.6% (93.3% to 97.3%) after exclusion of aberrant results from the Ukraine center. These results show a high level of agreement between SAMBA-II and a laboratory-based assay. SAMBA-II has a performance that is suitable to use as a VL point-of-care assay in remote settings.

Regulators of G protein signalling as pharmacological targets for the treatment of neuropathic pain.

Neuropathic pain, a specific type of chronic pain resulting from persistent nervous tissue lesions, is a debilitating condition that affects about 7% of the population. This condition remains particularly difficult to treat because of the poor understanding of its underlying mechanisms. Drugs currently used to alleviate this chronic pain syndrome are of limited benefit due to their lack of efficacy and the elevated risk of side effects, especially after a prolonged period of treatment. Although drugs targeting G protein-coupled receptors (GPCR) also have several limitations, such as progressive loss of efficacy due to receptor desensitization or unavoidable side effects due to wide receptor distribution, the identification of several molecular partners that contribute to the fine-tuning of receptor activity has raised new opportunities for the development of alternative therapeutic approaches. Regulators of G protein signalling (RGS) act intracellularly by influencing the coupling process and activity of G proteins, and are amongst the best-characterized physiological modulators of GPCR. Changes in RGS expression have been documented in a range of models of neuropathic pain, or after prolonged treatment with diverse analgesics, and could participate in altered pain processing as well as impaired physiological or pharmacological control of nociceptive signals. The present review summarizes the experimental data that implicates RGS in the development of pain with focus on the pathological mechanisms of neuropathic pain, including the impact of neuropathic lesions on RGS expression and, reciprocally, the influence of modifying RGS on GPCRs involved in the modulation of nociception as well as on the outcome of pain. In this context, we address the question of the relevance of RGS as promising targets in the treatment of neuropathic pain.

Post-stroke treatment with argon attenuated brain injury, reduced brain inflammation and enhanced M2 microglia/macrophage polarization: a randomized controlled animal study.

BACKGROUND: In recent years, argon has been shown to exert neuroprotective effects in an array of models. However, the mechanisms by which argon exerts its neuroprotective characteristics remain unclear. Accumulating evidence imply that argon may exert neuroprotective effects via modulating the activation and polarization of microglia/macrophages after ischemic stroke. In the present study, we analyzed the underlying neuroprotective effects of delayed argon application until 7 days after reperfusion and explored the potential mechanisms. METHODS: Twenty-one male Wistar rats underwent transient middle cerebral artery occlusion or sham surgery randomly for 2 h using the endoluminal thread model. Three hours after transient middle cerebral artery occlusion induction and 1 h after reperfusion, animals received either 50% vol Argon/50% vol O2 or 50% vol N2/50% vol O2 for 1 h. The primary outcome was the 6-point neuroscore from 24 h to d7 after reperfusion. Histological analyses including infarct volume, survival of neurons (NeuN) at the ischemic boundary zone, white matter integrity (Luxol Fast Blue), microglia/macrophage activation (Iba1), and polarization (Iba1/Arginase1 double staining) on d7 were conducted as well. Sample size calculation was performed using nQuery Advisor + nTerim 4.0. Independent t test, one-way ANOVA and repeated measures ANOVA were performed, respectively, for statistical analysis (SPSS 23.0). RESULTS: The 6-point neuroscore from 24 h to d7 after reperfusion showed that tMCAO Ar group displayed significantly improved neurological performance compared to tMCAO N2 group (p = 0.026). The relative numbers of NeuN-positive cells in the ROIs of tMCAO Ar group significantly increased compared to tMCAO N2 group (p = 0.010 for cortex and p = 0.011 for subcortex). Argon significantly suppressed the microglia/macrophage activation as revealed by Iba1 staining (p = 0.0076) and promoted the M2 microglia/macrophage polarization as revealed by Iba1/Arginase 1 double staining (p = 0.000095). CONCLUSIONS: Argon administration with a 3 h delay after stroke onset and 1 h after reperfusion significantly alleviated neurological deficit within the first week and preserved the neurons at the ischemic boundary zone 7 days after stroke. Moreover, argon reduced the excessive microglia/macrophage activation and promoted the switch of microglia/macrophage polarization towards the anti-inflammatory M2 phenotype. Studies making efforts to further elucidate the protective mechanisms and to benefit the translational application are of great value.

Stem cells from human apical papilla decrease neuro-inflammation and stimulate oligodendrocyte progenitor differentiation via activin-A secretion.

Secondary damage following spinal cord injury leads to non-reversible lesions and hampering of the reparative process. The local production of pro-inflammatory cytokines such as TNF-α can exacerbate these events. Oligodendrocyte death also occurs, followed by progressive demyelination leading to significant tissue degeneration. Dental stem cells from human apical papilla (SCAP) can be easily obtained at the removal of an adult immature tooth. This offers a minimally invasive approach to re-use this tissue as a source of stem cells, as compared to biopsying neural tissue from a patient with a spinal cord injury. We assessed the potential of SCAP to exert neuroprotective effects by investigating two possible modes of action: modulation of neuro-inflammation and oligodendrocyte progenitor cell (OPC) differentiation. SCAP were co-cultured with LPS-activated microglia, LPS-activated rat spinal cord organotypic sections (SCOS), and LPS-activated co-cultures of SCOS and spinal cord adult OPC. We showed for the first time that SCAP can induce a reduction of TNF-α expression and secretion in inflamed spinal cord tissues and can stimulate OPC differentiation via activin-A secretion. This work underlines the potential therapeutic benefits of SCAP for spinal cord injury repair.

Author Correction: Stem cells from human apical papilla decrease neuro­inflammation and stimulate oligodendrocyte progenitor differentiation via activin­A secretion.

In the original publication, sixth author's surname was incorrectly published as "Llyod" instead of "Lloyd". The correct name should read as "Amy Lloyd".

Commentary: A review of risk of hepatitis B and C transmission through biting or spitting.

A draft UK Parliamentary Bill sought to criminalize assaults on emergency workers through biting and spitting. This seemed to be based on a fear of bloodborne virus transmission. We undertook a literature search to clarify the risk of hepatitis infection from such exposures. We identified 245 possible papers and then reduced these to those relevant to HBV and HCV transmission through biting or spitting and the scientific plausibility. Nine papers were identified, reporting 16 possible cases of HBV (15 bites, 1 spitting) and 2 of HCV transmission (both bites). Only 3 HBV transmissions by bites and 1 by spitting and both HCV transmissions were felt to be plausible. Although both HBV DNA and HCV RNA can be found in the saliva of infected patients, it seems unlikely that there is enough to transmit infection unless there is blood contamination. In conclusion, the risk of acquiring HCV through spitting is negligible and is very low for HBV. The risk is also low for acquiring HBV and HCV through biting, especially if no blood is apparent in the saliva.

Inflammation-associated regulation of RGS in astrocytes and putative implication in neuropathic pain.

BACKGROUND: Regulators of G-protein signaling (RGS) are major physiological modulators of G-protein-coupled receptors (GPCR) signaling. Several GPCRs expressed in both neurons and astrocytes participate in the central control of pain processing, and the reduced efficacy of analgesics in neuropathic pain conditions may rely on alterations in RGS function. The expression and the regulation of RGS in astrocytes is poorly documented, and we herein hypothesized that neuroinflammation which is commonly observed in neuropathic pain could influence RGS expression in astrocytes. METHODS: In a validated model of neuropathic pain, the spared nerve injury (SNI), the regulation of RGS2, RGS3, RGS4, and RGS7 messenger RNA (mRNA) was examined up to 3 weeks after the lesion. Changes in the expression of the same RGS were also studied in cultured astrocytes exposed to defined activation protocols or to inflammatory cytokines. RESULTS: We evidenced a differential regulation of these RGS in the lumbar spinal cord of animals undergoing SNI. In particular, RGS3 appeared upregulated at early stages after the lesion whereas expression of RGS2 and RGS4 was decreased at later stages. Decrease in RGS7 expression was already observed after 3 days and outlasted until 21 days after the lesion. In cultured astrocytes, we observed that changes in the culture conditions distinctly influenced the constitutive expression of these RGS. Also, brief exposures (4 to 8 h) to either interleukin-1ß, interleukin-6, or tumor necrosis factor α caused rapid changes in the mRNA levels of the RGS, which however did not strictly recapitulate the regulations observed in the spinal cord of lesioned animals. Longer exposure (48 h) to inflammatory cytokines barely influenced RGS expression, confirming the rapid but transient regulation of these cell signaling modulators. CONCLUSION: Changes in the environment of astrocytes mimicking the inflammation observed in the model of neuropathic pain can affect RGS expression. Considering the role of astrocytes in the onset and progression of neuropathic pain, we propose that the inflammation-mediated modulation of RGS in astrocytes constitutes an adaptive mechanism in a context of neuroinflammation and may participate in the regulation of nociception.

Pre-differentiation of mesenchymal stromal cells in combination with a microstructured nerve guide supports peripheral nerve regeneration in the rat sciatic nerve model.

Many bioartificial nerve guides have been investigated pre-clinically for their nerve regeneration-supporting function, often in comparison to autologous nerve transplantation, which is still regarded as the current clinical gold standard. Enrichment of these scaffolds with cells intended to support axonal regeneration has been explored as a strategy to boost axonal regeneration across these nerve guides Ansselin et al. (1998). In the present study, 20 mm rat sciatic nerve defects were implanted with a cell-seeded microstructured collagen nerve guide (Perimaix) or an autologous nerve graft. Under the influence of seeded, pre-differentiated mesenchymal stromal cells, axons regenerated well into the Perimaix nerve guide. Myelination-related parameters, like myelin sheath thickness, benefitted from an additional seeding with pre-differentiated mesenchymal stromal cells. Furthermore, both the number of retrogradely labelled sensory neurons and the axon density within the implant were elevated in the cell-seeded scaffold group with pre-differentiated mesenchymal stromal cells. However, a pre-differentiation had no influence on functional recovery. An additional cell seeding of the Perimaix nerve guide with mesenchymal stromal cells led to an extent of functional recovery, independent of the differentiation status, similar to autologous nerve transplantation. These findings encourage further investigations on pre-differentiated mesenchymal stromal cells as a cellular support for peripheral nerve regeneration.

Characterisation of cell-substrate interactions between Schwann cells and three-dimensional fibrin hydrogels containing orientated nanofibre topographical cues.

The generation of complex three-dimensional bioengineered scaffolds that are capable of mimicking the molecular and topographical cues of the extracellular matrix found in native tissues is a field of expanding research. The systematic development of such scaffolds requires the characterisation of cell behaviour in response to the individual components of the scaffold. In the present investigation, we studied cell-substrate interactions between purified populations of Schwann cells and three-dimensional fibrin hydrogel scaffolds, in the presence or absence of multiple layers of highly orientated electrospun polycaprolactone nanofibres. Embedded Schwann cells remained viable within the fibrin hydrogel for up to 7 days (the longest time studied); however, cell behaviour in the hydrogel was somewhat different to that observed on the two-dimensional fibrin substrate: Schwann cells failed to proliferate in the fibrin hydrogel, whereas cell numbers increased steadily on the two-dimensional fibrin substrate. Schwann cells within the fibrin hydrogel developed complex process branching patterns, but, when presented with orientated nanofibres, showed a strong tendency to redistribute themselves onto the nanofibres, where they extended long processes that followed the longitudinal orientation of the nanofibres. The process length along nanofibre-containing fibrin hydrogel reached near-maximal levels (for the present experimental conditions) as early as 1 day after culturing. The ability of this three-dimensional, extracellular matrix-mimicking scaffold to support Schwann cell survival and provide topographical cues for rapid process extension suggest that it may be an appropriate device design for the bridging of experimental lesions of the peripheral nervous system.

'It's all in the message': the utility of personalised short message service (SMS) texts to remind patients at higher risk of STIs and HIV to reattend for testing-a repeat before and after study.

BACKGROUND: Patients at increased risk of sexually transmitted infections (STIs)/HIV acquisition are advised to reattend for retesting. A previous study showed that 'generic' text reminders did not improve reattendance. AIM: To assess if a personalised text message with increased contact information would increase reattendance rates of at-risk patients. METHODS: Patients who are at risk of future STIs, defined by having a current acute STI, attending for emergency contraception, commercial sex workers (CSWs) or men who have sex with men (MSM), were sent a text reminder to reattend for retesting 6 weeks after initial visit. Reattendance rates were measured for September to December 2012 (control group who received a generic text message) and February to May 2014 (intervention 'personalised message' group who received a text message containing their first name and ways to contact the clinic). Reattendance was counted within 4 months of the end of the initial episode of care. RESULTS: The reattendance rate was significantly higher for the intervention group: 149/266 (56%) than the control group: 90/273 (33%) (p=0.0001) and was also significantly higher in the intervention group than the control group in patients with the following risks: recent chlamydia (64/123 (52%) vs 43/121 (36%)) (p=0.03), recent gonorrhoea (41/64 (64%) vs 4/21 (19%)) (p=0.0003) and MSM (26/45 (58%) vs 3/18 (16%)) (p=0.006). New STI rates in the reattending intervention group and controls were 26/ 149 (17%) and 13/90 (14%) (n.s), respectively. CONCLUSIONS: Sending a personalised text message with increased contact information as a reminder for retesting increased reattendance rates by 23% in patients who are at higher risk of STIs.

The performance of non-NAAT point-of-care (POC) tests and rapid NAAT tests for chlamydia and gonorrhoea infections. An assessment of currently available assays.

OBJECTIVES: To identify point-of-care (POC) and rapid nucleic acid amplification techniques (NAATs) for the diagnosis of chlamydia and gonorrhoea and assess their utility. METHODS: Literature search for available POC and rapid NAATs. The performance from the best-performing assays were applied hypothetically to patients in the clinic in which 100 consecutive patients with chlamydia and 100 with gonorrhoea were diagnosed in 1737 and 4575 patients respectively, with 44/100 and 54/100 treated at first attendance, respectively. RESULTS: 11 POC and 1 rapid NAAT were identified. Published performances for the best POC for chlamydia (CRT) were: sensitivity 41%-87%, specificity 89%-99.6%. Our data suggest that if this assay was used instead of our current NAAT, for every 100 patients diagnosed currently, 23-46 extra patients would be treated at first attendance; 10-35 would go undiagnosed with 7-191 false-positives. Best chlamydia rapid NAAT (GeneXpert): sensitivity 97.5%-98.7%, specificity 99.4%-99.9%. Anticipated performance for every 100 patients diagnosed currently: 0 extra patients treated at first attendance, 1-3 undiagnosed, 0-2 false-positives. Best POC for gonorrhoea (GC Check): sensitivity 54%-70%, specificity 97%-98%. Anticipated performance for every 100 patients diagnosed currently: 14-18 extra patients treated at first attendance, 28-32 undiagnosed, 92-137 false-positives. Best rapid NAAT for gonorrhoea (GeneXpert): sensitivity 96%-100%, specificity 99.9%-100%. Anticipated performance for every 100 patients diagnosed currently: 0 extra patients treated at first attendance, 0-4 undiagnosed, 0-5 false-positives. Rapid NAAT would reduce time to treatment by 4 days for initially untreated patients. CONCLUSIONS: POC assays would need to be used in conjunction with a NAAT, increasing early treatment rates expense and false-positive results. The rapid NAAT could be used alone, with a reduction in average time-to-treat and a small reduction in sensitivity and specificity.

Olympics and Paralympics 2012 mass gathering in London: time-series analysis shows no increase in attendances at sexual health clinics.

OBJECTIVE: To determine whether the 2012 Olympic and Paralympic Games were associated with a change in the number of patients attending or diagnosed with a new sexually transmitted infection (STI) at sexual health clinics in London and Weymouth. METHODS: We undertook an interrupted time-series analysis of surveillance data from the Genitourinary Medicine Clinic Activity Dataset (GUMCAD) collected at 33 genitourinary medicine (GUM) clinics in London and Weymouth (where Games events were concentrated) between 2009 and 2012. Mixed-effects linear regression models of weekly attendance and diagnoses, incorporating temporal trends, bank holidays, categorical month and clinic closures, were used to test for the effect of the 'Olympic-Paralympic' period. We subdivided the 9-week 'Olympic-Paralympic' period (16 July 2012 to 17 September 2012) into five periods, including three Olympic weeks, two Paralympic weeks, pre-, post- and inter-Games weeks. We also compared characteristics of patients attending during the Olympic-Paralympic period and those attending during the same period in 2011. RESULTS: During the 3 weeks of the Olympics, there was a significant reduction in the number of new episode attendances (2020 fewer, 5.6% reduction (95% CI -8.2 to -2.9)) and the number of patients diagnosed with an STI (267 fewer, 4.8% reduction (95% CI -8.6 to -0.9)) compared to expected. There were no important differences in the profile of patients attending during the 2012 Olympic-Paralympic period and those attending during the same period in 2011. CONCLUSIONS: We conclude that a 'business-as-usual' approach to managing local sexual health clinics during the 2012 Olympic and Paralympics would have been appropriate.

Epidemiology of Sexually Transmitted Infections in Visitors for the London 2012 Olympic Games: A Review of Attendees at Sexual Health Services.

BACKGROUND: Mass gatherings and large sporting events, such as the Olympics, may potentially pose a risk of increased sexually transmitted infection (STI) transmission and increase burden on local STI services. The objectives of this analysis were to assess whether the STI profile of Olympic visitors differed from that of the local STI clinic population and to investigate what impact these visitors had on local STI services. METHODS: Self-administered questionnaires (completed by 29,292 patients) were used to determine the visitor status of patients attending 20 STI clinics, between July 20, 2012, and September 16, 2012, in the host cities, London and Weymouth. Using routine surveillance data from the Genitourinary Medicine Clinic Activity Dataset version 2, Olympic visitors were compared with usual attendees (local residents and non-Olympic visitors) in terms of their demographic characteristics, services utilized, and STIs diagnosed using univariate and multivariate methods. RESULTS: Compared with usual attendees, Olympic visitors were more likely to be heterosexual males (56.0% vs. 34.9%, P = 0.001), aged between 15 and 24 years of age (47.1% vs. 34.0%, P = 0.001), of white ethnicity (81.9% vs. 66.4%, P = 0.001), and born in Australasia, Asia, North America, or South America (18.8% vs. 12.0%, P = 0.006). Olympic visitors constituted 1% of new clinic attendances and were less likely to be diagnosed as having a new STI (adjusted odds ratio, 0.69; 95% confidence interval, 0.48-0.98; P = 0.040). CONCLUSIONS: In this first multisite study to examine the effect of Olympic visitors on local sexual health services, the 2012 Olympic Games was found to have minimal impact. This suggests that a "business as usual" approach would have been sufficient.

The utility of short message service (SMS) texts to remind patients at higher risk of STIs and HIV to reattend for testing: a controlled before and after study.

BACKGROUND: Patients attending for sexually transmitted infection (STI)/HIV testing may be at continuing risk of infection and advised to return for retesting at a later date. OBJECTIVES: To measure the impact of short message service (SMS) text reminders on the reattendance rates of patients who require repeat STI testing. METHODS: Reattendance rates were measured for two groups of higher risk patients: those listed for routine SMS text reminders in 2012 and a control group of patients from 2011 with the same risk profile who had not received any active recall. Reattendance was counted if it was within 4 months of the end of the episode of care. RESULTS: Reattendance rates were not statistically different between the text group 32% (89/274) and the control group 35% (92/266). Reattendance also was not statistically different between the text and control groups respectively in patients with the following risks: recent chlamydia 43/121 (36%) versus 41/123 (33%), recent gonorrhoea 4/21 (19%) versus 7/21 (33%), recent emergency contraception 27/60 (45%) versus 25/56 (45%) and other risks 7/27 (26%) versus 9/26 (35%). High rates of STIs were found in patients who reattended in both the text group (13/90, 14%) and control group (15/91, 17%) and at even higher rates at reattendance if the reason for recall was chlamydia infection at the initial visit: 9/43 (21%) in the text group and 10/41 (24%) in the control group. CONCLUSIONS: SMS texts sent as reminders to patients at higher risk of STIs and HIV did not increase the reattendance rate, when compared with standard advice, in this service which already has a high reattendance rate. STI rates were high in those patients who reattended.

Antenatal atazanavir: a retrospective analysis of pregnancies exposed to atazanavir.

INTRODUCTION: There are few data regarding the tolerability, safety, or efficacy of antenatal atazanavir. We report our clinical experience of atazanavir use in pregnancy. METHODS: A retrospective medical records review of atazanavir-exposed pregnancies in 12 London centres between 2004 and 2010. RESULTS: There were 145 pregnancies in 135 women: 89 conceived whilst taking atazanavir-based combination antiretroviral therapy (cART), "preconception" atazanavir exposure; 27 started atazanavir-based cART as "first-line" during the pregnancy; and 29 "switched" to an atazanavir-based regimen from another cART regimen during pregnancy. Gastrointestinal intolerance requiring atazanavir cessation occurred in five pregnancies. Self-limiting, new-onset transaminitis was most common in first-line use, occurring in 11.0%. Atazanavir was commenced in five switch pregnancies in the presence of transaminitis, two of which discontinued atazanavir with persistent transaminitis. HIV-VL < 50 copies/mL was achieved in 89.3% preconception, 56.5% first-line, and 72.0% switch exposures. Singleton preterm delivery (<37 weeks) occurred in 11.7% preconception, 9.1% first-line, and 7.7% switch exposures. Four infants required phototherapy. There was one mother-to-child transmission in a poorly adherent woman. CONCLUSIONS: These data suggest that atazanavir is well tolerated and can be safely prescribed as a component of combination antiretroviral therapy in pregnancy.

The Role of Length of Nerve Grafts in Combination with Free Functional Muscle Transplantation for Brachial Plexus Injury: A Single-Center Experience.

PURPOSE: Extensive lesions of the brachial plexus, or late cases, require free functional muscle grafts because the expected recovery time exceeds the critical threshold of 1.5 years, beyond which irreversible damage may be expected in the distal nerve stump and in the muscle. The reconstructive concept consists of a two-stage procedure where, in the first step, a nerve transfer is performed (from ipsi- or contralateral donor nerves). In the second step, after successful axonal regeneration within the graft has been confirmed, a free muscle transfer is performed. These grafts often exceed 40 cm in length, particularly for contralateral transfers. The purpose of this study was to assess whether robust motor recovery could be supported by such long nerve grafts. METHODS: From April 2004 to April 2023, a total of 327 free functional muscle transfers were performed, the nerve graft length ranging from 0 cm (direct coaptation) to 90 cm (serial grafts). Motor recovery was evaluated 1.5 years after surgery according to the MRC scale. RESULTS: A total of 208 patients were available for follow up. Direct coaptation yielded the best results, with 83% of patients reaching an M3 or M4 level of muscle strength. With the application of long (30-60 cm) grafts, 73% of the patients were classified as M3 or M4. The application of serial nerve grafts, however, only resulted in 18% of patients achieving a motor recovery rating of M3. CONCLUSIONS: These findings demonstrate that robust motor regeneration is supported by long (30-60 cm) nerve grafts, whereas serial nerve grafting results in a marked reduction in the quality of regeneration.

Pregnancy Management in HIV Viral Controllers: Twenty Years of Experience.

(1) Background: The evidence base for the management of spontaneous viral controllers in pregnancy is lacking. We describe the management outcomes of pregnancies in a series of UK women with spontaneous HIV viral control (<100 copies/mL 2 occasions before or after pregnancy off ART). (2) Methods: A multi-centre, retrospective case series (1999-2021) comparing pre- and post-2012 when guidelines departed from zidovudine-monotherapy (ZDVm) as a first-line option. Demographic, virologic, obstetric and neonatal information were anonymised, collated and analysed in SPSS. (3) Results: A total of 49 live births were recorded in 29 women, 35 pre-2012 and 14 post. HIV infection was more commonly diagnosed in first reported pregnancy pre-2012 (15/35) compared to post (2/14), p = 0.10. Pre-2012 pregnancies were predominantly managed with ZDVm (28/35) with pre-labour caesarean section (PLCS) (24/35). Post-2012 4/14 received ZDVm and 10/14 triple ART, p = 0.002. Post-2012 mode of delivery was varied (5 vaginal, 6 PLCS and 3 emergency CS). No intrapartum ZDV infusions were given post-2012 compared to 11/35 deliveries pre-2012. During pregnancy, HIV was detected (> 50 copies/mL) in 14/49 pregnancies (29%) (median 92, range 51-6084). Neonatal ZDV post-exposure prophylaxis was recorded for 45/49 infants. No transmissions were reported. (4) Conclusion: UK practice has been influenced by the change in guidelines, but this has had little impact on CS rates.