Complications of total laparoscopic hysterectomy: A retrospective study of cases performed by a single surgeon.

Hysterectomy is the most common gynaecological surgery and there are different techniques of performing hysterectomy. With the advent of laparoscopic technology, laparoscopic hysterectomy (LH) is rapidly gaining its ground. However, every surgery has its complications which are specific but also depends on various factors such as surgical sk[ills and experience of surgeons, levels of operative laparoscopy and patient populations. Aims and Objective: In this study, we evaluated the complications of total laparoscopic hysterectomy (TLH) and analysed the trend of complications, intraoperative and post-operative, over a period of time. Methods: It was a retrospective study conducted in the private care setting. All women who underwent hysterectomy for benign conditions from a 1 January 2003 to 31 December 2017, (15 years) were included in this study. A total of 3272 patients were operated during this period. All surgeries were performed by a single surgeon. Results: Intraoperative complications that occurred during surgery during the study period were 3 cases (0.09%) had bladder injury, 3 cases (0.09%) had bowel injury, 1 case (0.03%) had internal iliac vessel bleeding and 1 case(0.03%) needed conversion to vaginal hysterectomy due to cautery failure and post operative complications were 90 cases (2.75%) had vault bleeding, 2 cases (0.06%) had intestinal obstruction, 5 cases (0.15%) had paralytic ileus, 1 case (0.03%) had vesicovaginal fistula, 1 case(0.03%) had ureterovaginal fistula and 1 case (0.03%) had peritonitis. Conclusions: TLH is a very effective, patient-friendly and safe technique in the hands of experienced surgeons giving good quality of life to patients postoperatively.

Clinical Utility of Intravascular Ultrasound (IVUS) in Carotid Artery Interventions: A Systematic Review and Meta-analysis.

BACKGROUND: Carotid plaque morphology plays an important role in determining outcome of carotid artery stenting (CAS). Intravascular ultrasound (IVUS) and its extension VH (Virtual Histology)-IVUS evaluate plaque characteristics in real time and guide decision making during stenting. To date, there is no consensus about indications of IVUS and its validated methods. This systematic review and meta-analysis aims to evaluate the clinical utility of IVUS in carotid artery interventions (CAS) and develop a future consensus for research and practice parameters. METHODS: A systematic review and meta-analysis was performed of the English literature articles published till February 2021. Studies reporting on IVUS parameters and findings and also its performance compared with other imaging modalities were included in review. Pooled prevalence with 95% confidence intervals (CI) was calculated. The statistical analysis was conducted in R version 3.6.2. RESULTS: A total of 2015 patients from 29 studies were included. Proportional meta-analysis was performed on 1566 patients from 11 studies. In 9 studies, stroke/transient ischemic attack (TIA) had a pooled prevalence of 4% (95% CI 3%-5%) while asymptomatic stroke had a pooled prevalence of 46% (95% CI 31%-62%) in 4 studies following IVUS. Two studies reported that IVUS detected more plaque protrusion compared with angiography (n=33/396 vs 11/396). IVUS led to stent type or size change in 8 of 48 cases which were missed on angiography in 3 other studies. Concordance between VH-IVUS and true histology was good at 80% to 85% reported in 2 studies. CONCLUSIONS: This systematic review and meta-analysis showed, though IVUS fared better to computed tomography (CT)/magnetic resonance (MR) angiography for better stent selection during CAS, with low to moderate risk of bias in the studies included. However, large scale, preferably randomized controlled studies are needed to predict its role in determining clinical outcome.

Historical and future trends in emergency pituitary referrals: a machine learning analysis.

PURPOSE: Acute pituitary referrals to neurosurgical services frequently necessitate emergency care. Yet, a detailed characterisation of pituitary emergency referral patterns, including how they may change prospectively is lacking. This study aims to evaluate historical and current pituitary referral patterns and utilise state-of-the-art machine learning tools to predict future service use. METHODS: A data-driven analysis was performed using all available electronic neurosurgical referrals (2014-2021) to the busiest U.K. pituitary centre. Pituitary referrals were characterised and volumes were predicted using an auto-regressive moving average model with a preceding seasonal and trend decomposition using Loess step (STL-ARIMA), compared against a Convolutional Neural Network-Long Short-Term Memory (CNN-LSTM) algorithm, Prophet and two standard baseline forecasting models. Median absolute, and median percentage error scoring metrics with cross-validation were employed to evaluate algorithm performance. RESULTS: 462 of 36,224 emergency referrals were included (referring centres = 48; mean patient age = 56.7 years, female:male = 0.49:0.51). Emergency medicine and endocrinology accounted for the majority of referrals (67%). The most common presentations were headache (47%) and visual field deficits (32%). Lesions mainly comprised tumours or haemorrhage (85%) and involved the pituitary gland or fossa (70%). The STL-ARIMA pipeline outperformed CNN-LSTM, Prophet and baseline algorithms across scoring metrics, with standard accuracy being achieved for yearly predictions. Referral volumes significantly increased from the start of data collection with future projected increases (p < 0.001) and did not significantly reduce during the COVID-19 pandemic. CONCLUSION: This work is the first to employ large-scale data and machine learning to describe and predict acute pituitary referral volumes, estimate future service demands, explore the impact of system stressors (e.g. COVID pandemic), and highlight areas for service improvement.

Longitudinal analysis of T-cell receptor repertoires reveals persistence of antigen-driven CD4+ and CD8+ T-cell clusters in systemic sclerosis.

The T-cell receptor (TCR) is a highly polymorphic surface receptor that allows T-cells to recognize antigenic peptides presented on the major histocompatibility complex (MHC). Changes in the TCR repertoire have been observed in several autoimmune conditions, and these changes are suggested to predispose autoimmunity. Multiple lines of evidence have implied an important role for T-cells in the pathogenesis of Systemic Sclerosis (SSc), a complex autoimmune disease. One of the major questions regarding the roles of T-cells is whether expansion and activation of T-cells observed in the diseases pathogenesis is antigen driven. To investigate the temporal TCR repertoire dynamics in SSc, we performed high-throughput sequencing of CD4+ and CD8+ TCRß chains on longitudinal samples obtained from four SSc patients collected over a minimum of two years. Repertoire overlap analysis revealed that samples taken from the same individual over time shared a high number of TCRß sequences, indicating a clear temporal persistence of the TCRß repertoire in CD4+ as well as CD8+ T-cells. Moreover, the TCRßs that were found with a high frequency at one time point were also found with a high frequency at the other time points (even after almost four years), showing that frequencies of dominant TCRßs are largely consistent over time. We also show that TCRß generation probability and observed TCR frequency are not related in SSc samples, showing that clonal expansion and persistence of TCRßs is caused by antigenic selection rather than convergent recombination. Moreover, we demonstrate that TCRß diversity is lower in CD4+ and CD8+ T-cells from SSc patients compared with memory T-cells from healthy individuals, as SSc TCRß repertoires are largely dominated by clonally expanded persistent TCRß sequences. Lastly, using "Grouping of Lymphocyte Interactions by Paratope Hotspots" (GLIPH2), we identify clusters of TCRß sequences with homologous sequences that potentially recognize the same antigens and contain TCRßs that are persist in SSc patients. In conclusion, our results show that CD4+ and CD8+ T-cells are highly persistent in SSc patients over time, and this persistence is likely a result from antigenic selection. Moreover, persistent TCRs form high similarity clusters with other (non-)persistent sequences that potentially recognize the same epitopes. These data provide evidence for an antigen driven expansion of CD4+/CD8+ T-cells in SSc.

The role of altered glycosylation in human nucleus pulposus cells in inflammation and degeneration.

Intervertebral disc (IVD) degeneration causes low-back pain through disc compression, prolapse and herniation. Inflammation of the IVD and subsequent degeneration produce altered glycosylation profiles in several animal models of IVD injury and ageing, although the function of this altered glycosylation pattern in a human is unknown. Altered N-glycome, specifically sialylated and fucosylated N-glycosylation motif expression, might play a role in inflammation and disease progression. Healthy (foetal and adolescent idiopathic scoliosis) and degenerated (lumbar degeneration) human IVD glycosylation patterns were studied using lectin histochemistry. Small-molecule fluorinated sugar analogues (3Fax-Peracetyl Neu5Ac; 2F-Peracetyl-Fucose) were used to inhibit sialylation and fucosylation in an in vitro model of inflammation, to investigate their effects on the glycosignature, cell metabolism, extracellular matrix synthesis and cell migration. The effects of interleukin (IL)-1ß, tumour necrosis factor (TNF)-α and IL-6 on glycosylation in human nucleus pulposus cells were investigated by lectin histochemistry, PCR and enzyme-linked immunosorbent assay (ELISA). In the in vitro model of IVD degeneration, cytokine-induced inflammation-induced hypersialylation was observed, as indicated by Sambucus nigra I binding. However, this modification was inhibited by the sialyltransferase inhibitor. Inhibition of sialylation and fucosylation modulates cell migration and protein translation of catabolic enzymes in response to inflammation. The altered patterns of glycosylation in human tissue in degeneration was consistent with previous IVD studies in murine, bovine and ovine models. The present study was the first functional investigation of glycosylation in human degenerated IVD, elucidating the role of the glycome in disease progression and identified potential therapeutic targets for future regenerative therapies.

The role of innate immune cells in systemic sclerosis in the context of autologous hematopoietic stem cell transplantation.

Systemic sclerosis (SSc) is a complex, heterogeneous autoimmune connective tissue disease. Autologous hematopoietic stem-cell transplantation (AHSCT) has emerged as a valuable treatment option for rapidly progressive diffuse cutaneous SSc (dcSSc) patients, and thus far is the only treatment that has been shown to have a long-term clinical benefit. AHSCT is thought to reintroduce immune homeostasis through elimination of pathogenic self-reactive immune cells and reconstitution of a new, tolerant immune system. However, the mechanism of action underlying this reset to tolerance remains largely unknown. In this study we review the immune mechanisms underlying AHSCT for SSc, with a focus on the role of the innate immune cells, including monocytes and natural killer (NK) cells, in restoring immune balance after AHSCT.

Microbial biofilms in nature: unlocking their potential for agricultural applications.

Soil environments are dynamic and the plant rhizosphere harbours a phenomenal diversity of micro-organisms which exchange signals and beneficial nutrients. Bipartite beneficial or symbiotic interactions with host roots, such as mycorrhizae and various bacteria, are relatively well characterized. In addition, a tripartite interaction also exists between plant roots, arbuscular mycorrhizal fungi (AMF) and associated bacteria. Bacterial biofilms exist as a sheet of bacterial cells in association with AMF structures, embedded within a self-produced exopolysaccharide matrix. Such biofilms may play important functional roles within these tripartite interactions. However, the details about such interactions in the rhizosphere and their relevant functional relationships have not been elucidated. This review explores the current understanding of naturally occurring microbial biofilms, and their interaction with biotic surfaces, especially AMF. The possible roles played by bacterial biofilms and the potential for their application for a more productive and sustainable agriculture is discussed in this review.

Cell-free soluble expression of the membrane protein PsbS.

Photosystem II subunit S (PsbS) is a membrane protein that plays an exclusive role in non-photochemical quenching for photoprotection of plants under high-light conditions. The activation mechanism of PsbS and its pH-induced conformational changes are currently unknown. For structural investigation of PsbS, effective synthesis of PsbS with selective isotope or electron-spin labels or non-natural amino acids incorporated would be a great asset. Here we present cell-free (CF) expression as a successful method for in vitro production of PsbS that would allow such incorporation. The addition of several detergents, liposomes and lipid nanodiscs was tested for achieving soluble CF expression of PsbS. We have optimized the CF method to yield soluble PsbS of ∼500 ng/µl using a continuous-exchange method at 30 °C, along with a successful purification and refolding of PsbS in n-Dodecyl ß-D-maltoside (ß-DM) detergent. We expect that the presented protocols are transferrable for in vitro expression of other membrane proteins of the Light-Harvesting Complex family.

Utility of 18 F-FDG PET/CT in pre-surgical risk stratification of patients with breast cancer.

OBJECTIVE: To determine the correlation between fluorine-18-fluorodeoxyglucose (18F-FDG) uptake values and clinicopathological prognostic markers using preoperative 18F-FDG positron emission tomography/computed tomography (PET/CT) in primary breast cancer (BC). SUBJECTS AND METHODS: One hundred and twelve patients with primary BC were studied prospectively. Pretreatment 18F-FDG PET/CT was performed. Maximum standardized uptake values (SUVmax) were compared with various clinicopathological variables. RESULTS: In a univariate analysis, SUVmax correlated well with the following prognostic variables: T stage, absence of progesterone receptor (PR), absence of estrogen receptor (ER), triple negative lesions (ER/PR and Her 2 negative) and high histologic grade. Metastatic lesions and ductal lesions had higher SUVmax than lobular carcinoma. No significant correlation was found between SUVmax,and human epidermal growth factor receptor 2 (Her-2) statusor perineural and lymphovascular invasion. Multivariate analyses showed that breast density, tumor size and PR negativity were significantly correlated with SUVmax (P=0.046 and 0.009, respectively). CONCLUSION: The pre-treatment tumor SUVmax could be utilized as an independent imaging biomarker of the tumor aggressiveness and poor prognosis. Risk stratification based on this index could play a pivotal role in alteration of treatment planning, such as neoadjuvant chemotherapy (precision oncology).

Bone marrow mononuclear cell therapy in ischaemic stroke: a systematic review.

Bone marrow mononuclear cell (BM-MNC) therapy has emerged as a potential therapy for the treatment of stroke. We performed a systematic review of published studies using BM-MNC therapy in patients with ischaemic stroke (IS). Literature was searched using MEDLINE, PubMed, EMBASE, Trip Database, Cochrane library and clinicaltrial.gov to identify studies on BM-MNC therapy in IS till June, 2016. Data were extracted independently by two reviewers. STATA version 13 was used for carrying out meta-analysis. We included non-randomized open-label, single-arm and non-randomized comparative studies or randomized controlled trials (RCTs) if BM-MNCs were used to treat patients with IS in any phase after the index stroke. One randomized trial, two non-randomized comparative trials and four single-arm open-label trials (total seven studies) involving 227 subjects (137 patients and 90 controls) were included in the systematic review and meta-analysis. The pooled proportion for favourable clinical outcome (modified Rankin Scale score ≤2) in six studies involving 122 subjects was 29% (95% CI 0.16-0.43) who were exposed to BM-MNCs and pooled proportion for favourable clinical outcome of 69 subjects (taken from two trials) who did not receive BM-MNCs was 20% (95% CI 0.12-0.32). The pooled difference in the safety outcomes was not significant between both the groups. Our systematic review suggests that BM-MNC therapy is safe up to 1 year post-intervention and is feasible; however, its efficacy in the case of IS patients is debatable. Well-designed randomized controlled trials are required to provide more information on the efficacy of BM-MNC transplantation in patients with IS.

High-dose statin therapy and risk of intracerebral hemorrhage: a meta-analysis.

Statin plays a major role in the primary and secondary prevention of cardiovascular disease (CVD). Inconsistent findings in the studies have been observed toward the risk of intracerebral hemorrhage (ICH) using higher dose of statin. To examine this issue, we performed a meta-analysis of randomized controlled trials (RCTs) to assess the association between higher dose of various statins and risk of ICH among patients with CVD. Literature was searched for studies published before June 10, 2015, using electronic database 'PubMed', 'EMBASE', and 'Google Scholar' as well as from many trial databases. The following search terms were used: 'Statin therapy' AND 'Cardiovascular Disease', AND 'Dose' AND 'Intracerebral hemorrhage', AND 'Randomized Controlled Trials' AND 'High Dose Statin'. High dose of statins was defined as atorvastatin 80 mg, simvastatin 80 mg, pravastatin 40 mg, rosuvastatin 20 mg per day. Fixed-effect model was used to estimate the risk ratio (RR) and 95% confidence interval (CI) if heterogeneity was <50%; otherwise, random-effect model was used. Begg's funnel plot was used to assess the publication bias. Seven RCTs involving 31,099 subjects receiving high-dose statin and 31,105 subjects receiving placebo were analyzed in our meta-analysis. A significant risk of ICH was observed in subjects with higher dose of statin (RR = 1.53; 95% CI: 1.16-2.01; P = 0.002). There was no difference in all-cause mortality between the two groups (RR = 0.95; 95% CI: 0.86-1.06; P = 0.36). No publication bias was observed through Begg's funnel plot. Higher dose of statins was found to be associated with the risk of ICH. Future studies are needed to confirm these findings.

Whole-brain mapping of structural connectivity in infants reveals altered connection strength associated with growth and preterm birth.

Cerebral white-matter injury is common in preterm-born infants and is associated with neurocognitive impairments. Identifying the pattern of connectivity changes in the brain following premature birth may provide a more comprehensive understanding of the neurobiology underlying these impairments. Here, we characterize whole-brain, macrostructural connectivity following preterm delivery and explore the influence of age and prematurity using a data-driven, nonsubjective analysis of diffusion magnetic resonance imaging data. T1- and T2-weighted and -diffusion MRI were obtained between 11 and 31 months postconceptional age in 49 infants, born between 25 and 35 weeks postconception. An optimized processing pipeline, combining anatomical, and tissue segmentations with probabilistic diffusion tractography, was used to map mean tract anisotropy. White-matter tracts where connection strength was related to age of delivery or imaging were identified using sparse-penalized regression and stability selection. Older children had stronger connections in tracts predominantly involving frontal lobe structures. Increasing prematurity at birth was related to widespread reductions in connection strength in tracts involving all cortical lobes and several subcortical structures. This nonsubjective approach to mapping whole-brain connectivity detected hypothesized changes in the strength of intracerebral connections during development and widespread reductions in connectivity strength associated with premature birth.

Efficacy of stem cell in improvement of left ventricular function in acute myocardial infarction--MI3 Trial.

BACKGROUND & OBJECTIVES: Acute myocardial infarction (AMI) is characterized by irreparable and irreversible loss of cardiac myocytes. Despite major advances in the management of AMI, a large number of patients are left with reduced left ventricular ejection fraction (LVEF), which is a major determinant of short and long term morbidity and mortality. A review of 33 randomized control trials has shown varying improvement in left ventricular (LV) function in patients receiving stem cells compared to standard medical therapy. Most trials had small sample size and were underpowered. This phase III prospective, open labelled, randomized multicenteric trial was undertaken to evaluate the efficacy in improving the LVEF over a period of six months, after injecting a predefined dose of 5-10 × 10 [8] autologous mononuclear cells (MNC) by intra-coronary route, in patients, one to three weeks post ST elevation AMI, in addition to the standard medical therapy. METHODS: In this phase III prospective, multicentric trial 250 patients with AMI were included and randomized into stem cell therapy (SCT) and non SCT groups. All patients were followed up for six months. Patients with AMI having left ventricular ejection fraction (LVEF) of 20-50 per cent were included and were randomized to receive intracoronary stem cell infusion after successfully completing percutaneous coronary intervention (PCI). RESULTS: On intention-to-treat analysis the infusion of MNCs had no positive impact on LVEF improvement of ≥ 5 per cent. The improvement in LVEF after six months was 5.17 ± 8.90 per cent in non SCT group and 4.82 ± 10.32 per cent in SCT group. The adverse effects were comparable in both the groups. On post hoc analysis it was noted that the cell dose had a positive impact when infused in the dose of ≥ 5 X 10 [8] (n=71). This benefit was noted upto three weeks post AMI. There were 38 trial deviates in the SCT group which was a limitation of the study. INTERPRETATION & CONCLUSIONS: Infusion of stem cells was found to have no benefit in ST elevation AMI. However, the procedure was safe. A possible benefit was seen when the predefined cell dose was administered which was noted upto three weeks post AMI, but this was not significant and needs confirmation by larger trials.

A randomized double-blind, placebo-controlled trial to evaluate the safety and efficacy of live Bifidobacterium longum CECT 7347 (ES1) and heat-treated Bifidobacterium longum CECT 7347 (HT-ES1) in participants with diarrhea-predominant irritable bowel syndrome.

To determine the efficacy of the probiotic Bifidobacterium longum CECT 7347 (ES1) and postbiotic heat-treated Bifidobacterium longum CECT 7347 (HT-ES1) in improving symptom severity in adults with diarrhea-predominant irritable bowel syndrome (IBS-D), a randomised, double-blind, placebo-controlled trial with 200 participants split into three groups was carried out. Two capsules of either ES1, HT-ES1 or placebo were administered orally, once daily, for 84 days (12 weeks). The primary outcome was change in total IBS-Symptom Severity Scale (IBS-SSS) score from baseline, compared to placebo. Secondary outcome measures were stool consistency, quality of life, abdominal pain severity and anxiety scores. Safety parameters and adverse events were also monitored. The change in IBS-SSS scores from baseline compared to placebo, reached significance in the ES1 and HT-ES1 group, on Days 28, 56 and 84. The decrease in mean IBS-SSS score from baseline to Day 84 was: ES1 (-173.70 [±75.60]) vs placebo (-60.44 [±65.5]) (p < .0001) and HT-ES1 (-177.60 [±79.32]) vs placebo (-60.44 [±65.5]) (p < .0001). Secondary outcomes included changes in IBS-QoL, APS-NRS, stool consistency and STAI-S and STAI-T scores, with changes from baseline to Day 84 being significant in ES1 and HT-ES1 groups, compared to the placebo group. Both ES1 and HT-ES1 were effective in reducing IBS-D symptom severity, as evaluated by measures such as IBS-SSS, IBS-QoL, APS-NRS, stool consistency, and STAI, in comparison to the placebo. These results are both statistically significant and clinically meaningful, representing, to the best of the authors' knowledge, the first positive results observed for either a probiotic or postbiotic from the same strain, in this particular population.

What is already known on this topicIBS is a chronic functional gastrointestinal disorder characterized by abdominal pain, bloating and abnormalities in stool frequency or form. The gut microbiota of people living with IBS differs markedly to the microbiota of healthy individuals. Gut microbiota may play a key role in IBS aetiology and IBS symptoms may be alleviated by modulating the gut microbiota. Several proposed ways to modulate gut health include normalizing the gut microbiota, preventing the overgrowth of pathogenic bacteria, modulating visceral afferent pathways, and enhancing intestinal barrier function. However, significant heterogeneity between studies, study quality and population, study design and concerns about sample size have limited national and supranational bodies from recommending probiotics for IBS. Further well-powered, randomized, repeatable and controlled trials are warranted.What this study addsThe results of this study substantially contribute to the IBS research field, firstly by providing clinically meaningful and statistically significant results from a rigorous, well designed randomized, placebo-controlled trial and secondly, by exploring the use of postbiotics in IBS, an area of research still in its infancy. Probiotic (ES1) and postbiotic (HT-ES1) supplementation significantly reduced IBS symptom severity scores compared to placebo. This study met primary and secondary outcomes and strongly suggest that ES1 and HT-ES1 could be beneficial in the management of IBS.How this study might affect research, practice, or policyThis study adds to the current evidence base, supporting the use of probiotic/postbiotics for IBS. This research could be used to inform health professionals about using probiotics in IBS and help improve the quality of life and wellbeing for people living with the condition.

Improved axonal regeneration of transected spinal cord mediated by multichannel collagen conduits functionalized with neurotrophin-3 gene.

Functionalized biomaterial scaffolds targeted at improving axonal regeneration by enhancing guided axonal growth provide a promising approach for the repair of spinal cord injury. Collagen neural conduits provide structural guidance for neural tissue regeneration, and in this study it is shown that these conduits can also act as a reservoir for sustained gene delivery. Either a G-luciferase marker gene or a neurotrophin-3-encoding gene, complexed to a non-viral, cyclized, PEGylated transfection vector, was loaded within a multichannel collagen conduit. The complexed genes were then released in a controlled fashion using a dual release system both in vitro and in vivo. For evaluation of their biological performance, the loaded conduits were implanted into the completely transected rat thoracic spinal cord (T8-T10). Aligned axon regeneration through the channels of conduits was observed one month post-surgery. The conduits delivering neurotrophin-3 polyplexes resulted in significantly increased neurotrophin-3 levels in the surrounding tissue and a statistically higher number of regenerated axons versus the control conduits (P<0.05). This study suggests that collagen neural conduits delivering a highly effective non-viral therapeutic gene may hold promise for repair of the injured spinal cord.

Challenges and strategies in the repair of ruptured annulus fibrosus.

Lumbar discectomy is the surgical procedure most frequently performed for patients suffering from low back pain and sciatica. Disc herniation as a consequence of degenerative or traumatic processes is commonly encountered as the underlying cause for the painful condition. While discectomy provides favourable outcome in a majority of cases, there are conditions where unmet requirements exist in terms of treatment, such as large disc protrusions with minimal disc degeneration; in these cases, the high rate of recurrent disc herniation after discectomy is a prevalent problem. An effective biological annular repair could improve the surgical outcome in patients with contained disc herniations but otherwise minor degenerative changes. An attractive approach is a tissue-engineered implant that will enable/stimulate the repair of the ruptured annulus. The strategy is to develop three-dimensional scaffolds and activate them by seeding cells or by incorporating molecular signals that enable new matrix synthesis at the defect site, while the biomaterial provides immediate closure of the defect and maintains the mechanical properties of the disc. This review is structured into (1) introduction, (2) clinical problems, current treatment options and needs, (3) biomechanical demands, (4) cellular and extracellular components, (5) biomaterials for delivery, scaffolding and support, (6) pre-clinical models for evaluation of newly developed cell- and material-based therapies, and (7) conclusions. This article highlights that an interdisciplinary approach is necessary for successful development of new clinical methods for annulus fibrosus repair. This will benefit from a close collaboration between research groups with expertise in all areas addressed in this review.

Miliary sarcoidosis with secondary Sjogren's syndrome.

We report a case of miliary sarcoidosis with secondary Sjogren's in a 45-year-old male who presented with symptoms of sicca syndrome in the form of dryness of eyes and mouth with parotid swelling. Computed tomography thorax showed mediastinal and hilar lymphadenopathy, bilateral miliary opacities in lung parenchyma. Whole body FDG PET/CT showed involvement of both parotids, liver, diffuse uptake in lungs, mediastinal and retroperitoneal lymph nodes. Patient is on treatment with prednisolone and has responded well.

COVID-19 nasopharyngeal swab and cribriform fracture.

Since the start of the pandemic, over 400 million COVID-19 swab tests have been conducted in the UK with a non-trivial number associated with skull base injury. Given the continuing use of nasopharyngeal swabs, further cases of swab-associated skull base injury are anticipated. We describe a 54-year-old woman presenting with persistent colourless nasal discharge for 2 weeks following a traumatic COVID-19 nasopharyngeal swab. A ß2-transferrin test confirmed cerebrospinal fluid (CSF) rhinorrhoea and a high-resolution sinus computed tomography (CT) scan demonstrated a cribriform plate defect. Magnetic resonance imaging showed radiological features of idiopathic intracranial hypertension (IIH): a Yuh grade V empty sella and thinned anterior skull base. Twenty-four hour intracranial pressure (ICP) monitoring confirmed raised pressures, prompting insertion of a ventriculoperitoneal shunt. The patient underwent CT cisternography and endoscopic transnasal repair of the skull base defect using a fluorescein adjuvant, without complications. A systematic search was performed to identify cases of COVID-19 swab-related injury. Eight cases were obtained, of which three presented with a history of IIH. Two cases were complicated by meningitis and were managed conservatively, whereas six required endoscopic skull base repair and one had a ventriculoperitoneal shunt inserted. A low threshold for high-resolution CT scanning is suggested for patients presenting with rhinorrhoea following a nasopharyngeal swab. The literature review suggests an underlying association between IIH, CSF rhinorrhoea and swab-related skull base injury. We highlight a comprehensive management pathway for these patients, including high-resolution CT with cisternography, ICP monitoring, shunt and fluorescein-based endoscopic repair to achieve the best standard of care.

Autonomous functioning thyroid nodule successfully treated with radioiodine in a 3 and a half-year-old boy.

Hyperthyroidism is rare in paediatric age group, the most common cause being Graves' disease. Very few cases of autonomous functioning thyroid nodule (AFTN) as a cause of paediatric hyperthyroidism have been reported. We herein report a case of AFTN in a 3 and a half-year-old boy who had become symptomatic with a swelling in the neck and hypermetabolic features at the age of 8 months. He was successfully treated with 131I radioablation, which rendered him euthyroid.