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Titanium is a commonly used inert bio-implant material within the medical and dental fields. Although the use of titanium is thought to be safe with a high success rate, in some cases, there are rare reports of problems caused by titanium. Even though various recent advancement in the implant has been implicated in this era, still titanium is gold stranded among dental implant materials. In most of these problematic reports, only individual reports are dominant and comprehensive reporting has not been performed. This comprehensive article has been prepared to review the toxicity of titanium and its alloy materials in the field of dentistry. Keywords: Allergy; implant toxicity; titanium implants; titanium particles; Yellow nail syndrome

Surgical Precision to restore both biologic and aesthetic demands of patients is most important in today’s periodontal practice. Technical skills of the clinician are challenged by the limited range of visual acuity. Periodontal microsurgery increases the efficiency of basic periodontal surgical procedures by improving normal vision through magnification along with advance lighting system. Incorporation of magnification in periodontal practice gives precise outcomes which are not achieved with traditional macro surgery in terms of improved visual acuity, ergonomic benefits, decreased patient morbidity, enhanced patient acceptance, rapid healing, passive wound closure and reduced tissue trauma.The aim of this review is to enlighten about periodontal microsurgery, its role in magnification, micro-surgical instrumentation, microsurgical suturing techniques, clinical advancement and application. Keywords: Ergonomics; magnification; microsurgery; precision; techniques

A previously independent 83-year-old lady presents with acute confusion, decreased mobility, urinary retention, and constipation, having recently received a course of oral acyclovir for shingles. The patient was noted to have extensive bruising to her upper limbs, and blood tests showed raised inflammatory markers with low platelet count, although this remained above 75 × 109/L. Her confusion on a background of shingles raised the differential diagnosis of varicella-zoster virus (VZV) encephalitis. CT head and MRI brain showed no acute intracranial abnormality. Lumbar puncture yielded frankly haemorrhagic cerebrospinal fluid (CSF), but viral polymerase chain reaction (PCR) testing was negative for the varicella-zoster virus. She later developed further right shoulder pain and right lower limb weakness three days post-initial lumbar puncture. Repeat CT head was unremarkable. MRI spine showed extensive spinal subarachnoid haemorrhage, with possible cervical arteriovenous malformation and L5/S1 spinal nerve compression. The patient was managed conservatively with dexamethasone and inpatient physiotherapy support. She was discharged after a long hospital stay at a new mobility baseline requiring hoist transfers.

Background/Aims Acquired hypocomplementemia occurs through immune complex-mediated diseases, as seen in systemic lupus erythematosus (SLE), idiopathic membranoproliferative glomerulonephritis (MPGN) and cryoglobulinemia. Infective causes are less common, although chronic bacterial and viral infections causing glomerulonephritis (GN) and vasculitis have been reported. Bacterial infections causing chronic osteomyelitis, endocarditis and visceral abscesses have all been implicated, whilst hepatitis B is the only virus known to cause severe GN/ vasculitis leading to low complement levels. Severe meningococcal disease is an established cause of acquired hypocomplementemia, typically associated with Nisseria Meningitidis. Parvovirus B19 is an infection exclusive to humans, usually manifesting as fifth disease, a mild illness characterised by a rash, fever and runny nose. Less common systemic effects include hydrops fetalis, thrombocytopenia, neutropenia, neurological sequalae (including encephalopathy, aseptic meningitis, neuropathy and neuralgic amyotrophy), myocarditis and hepatitis. Arthropathy is by far the most common manifestation in adults, affecting 60% of females and 30% of males. Methods The literature on Parvovirus B19 and hypocomplementemia is sparse, limited to case reports and comparative studies, the pathogenicity of which stems from glomerulonephritis, consequently resulting in low complement levels. We present a case series of 2 patients with Parvovirus B19 infection and acquired hypocomplementemia between 2016-2020. Results Patient A, a 26-year-old female, presented with a vasculitic rash on her legs and arthralgia affecting her hands and knees, refractory to oral prednisolone and hydroxychloroquine. She was found to have low complement levels (C3 0.61 g/l and C4 0.03 g/l), whilst ANA, ENA and ANCA testing was negative. She also had a negative rheumatoid factor and anti-CCP antibody, and a normal serum protein: creatinine (6 mg/mmol). Immunoglobulins were within normal range (IgG 8.7 g/l, IgA 0.80 g/l, IgM 2.41 g/l) and a serum protein electrophoresis was normal. Hepatitis and HIV serology was also negative. Patient B, a 34-year-old female, 9 weeks pregnant, presented with polyarthralgia, fever and a maculopapular rash, with normal inflammatory markers and a normal serum protein: creatinine (9 mg/mmol). Her complement was low (C3 0.57 g/l and C4 Conclusion We recommend that clinicians consider acute viral illness in patients presenting with vasculitis and hypocomplementemia. If diagnosis and treatment can be established early, patients can avoid the need for long term immunosuppression. Disclosure A. Gharatya: None. C. Nelson: None. S. Melath: None.

Background Fibroblast Ggrowth factor-23 (FGF-23) is a phosphate regulator primarily expressed by osteocytes. Excess FGF-23 leads to decreased hydroxylation of 25-hydroxyvitamin D and poor renal phosphate reabsorption. This leads to hypophosphataemia and represents a rare cause of osteomalacia, resulting in bone oedema and stress fractures. Methods A 57-year-old man with known skin psoriasis presented with a two-year history of left foot and ankle pain. On examination, he had chronic dactylitis of the left, big toe associated with skin psoriasis and nail pitting. Serum inflammatory markers were normal, and autoimmune screens for RF, anti-CCP and HLA-B27 were negative. Bilateral foot and ankle X-rays showed no bony abnormality. This was diagnosed as likely psoriatic arthritis and MRI showed talar bone oedema, felt to be related to the inflammatory arthritis. Symptoms settled well on non-steroidal anti-inflammatories. However, he presented two months later with focal distal tibial pain and swelling. There was no history of trauma. Repeat MRI showed proximal migration of bone oedema with stress fractures of the left posterior talus and distal tibial metaphysis. Results Blood tests showed low phosphate, elevated PTH, normal adjusted calcium, raised ALP and low 25-hydroxyvitamin D. DEXA scan confirmed osteoporosis of the hip. The patient was commenced on intravenous three-monthly pamidronate and colecalciferol (vitamin D3) supplements. Despite this, the patient continued to have migratory joint pain affecting the ankle, hip and sacroiliac joints. Methotrexate was prescribed to improve his psoriasis, but whilst his skin improved his legs remained painful. A repeat MRI showed new insufficiency fractures to the left talus and right neck of femur. Although taking colecalciferol supplementation, his serum phosphate remained low (0.5mmol/L). On further investigation, Myeloma screen and FDG PET were normal but he was noted to have an increased fractional urinary phosphate excretion indicating poor renal phosphate reabsorption. Serum FGF-23 assay was elevated at 131 mIU/L (normal Conclusion This case illustrates the need for thorough investigation of symptomatic, treatment-refractory hypophosphataemia. Although mild hypophosphatemia could indicate adult onset rickets, rarer causes such as FGF-23 secreting tumours should be considered. These tumours are notoriously difficult to locate; 68-Gallium DOTATATE PET may offer superior specificity to other imaging modalities, including FDG-PET, in detecting these mesenchymal tumours. FGF-23 decreases hydroxylation of vitamin D3 and renal phosphate reabsorption, and calcitriol alongside phosphate supplementation is advisable for symptomatic management until definitive treatment. Disclosures K. Fisher None. S. Melath None. S. Patel None.

Background Fibroblast growth factor-23 (FGF-23) is a phosphate regulator primarily expressed by osteocytes. Excess FGF-23 leads to decreased hydroxylation of 25-hydroxyvitamin D and poor renal phosphate reabsorption. This leads to hypophosphatemia and represents a rare cause of osteomalacia, resulting in bone oedema and stress fractures. Methods A 57-year-old man with known skin psoriasis presented with a two-year history of left foot and ankle pain. On examination, he had chronic dactylitis of the big toe and extra-articular features included skin psoriasis on the scalp, elbows, knees, and nail pitting. Serum inflammatory markers were normal, and autoimmune screens for RF, anti-CCP and HLA-B27 were negative. Bilateral foot and ankle X-rays showed no bony abnormality. This was diagnosed as likely psoriatic arthritis and MRI showed talar bone oedema, felt to be related to inflammatory arthritis. Symptoms settled well on non-steroidal anti-inflammatories. However, he presented with focal distal tibial swelling and pain, two months later. There was no history of trauma, Repeat MRI2 showed proximal migration of bone oedema with stress fractures of the left posterior talus and distal tibial metaphysis. Bloods tests showed low phosphate, elevated PTH, normal adjusted calcium, raised ALP and low 25-OH vitamin D. DEXA scan confirmed osteoporosis of the hip. The patient was commenced on bisphosphonate with 25-hydroxyvitamin D and phosphate supplementation. Despite this, the patient continued to have migratory joint pain affecting the ankle, hip and sacroiliac joints. Methotrexate was started for psoriasis and whilst his skin improved, his pain remained and further MRI showed left talar and right neck of femur insufficiency fractures. Results Although taking vitamin D3 supplementation, he remained hypophosphateamic 0.5mmol/L. Myeloma screen and PET FDG were normal. However, he was noted to have an increased fractional urinary phosphate excretion indicating poor renal phosphate reabsorption. One possible cause of this is elevated FGF-23, which was confirmed with FGF-23 assay (include levels and normal range). The patient underwent PET Ga-DOTATE imaging, utilising a tracer specific for somatostatin receptors found on neuroendocrine tumours. This showed a T9 pedicle lesion and a CT-guided biopsy confirmed a mesenchymal tumour as the cause of FGF-23 secretion, resulting in TBMO and insufficiency fractures. The patient has become asymptomatic on calcitriol and phosphate supplementation. He is now being considered for radiofrequency ablation therapy. Conclusion This case illustrates the need for a thorough investigation of symptomatic, treatment-refractory hypophosphataemia. Although mild hypophosphatemia could indicate adult-onset rickets, rarer causes such as FGF-23 secreting tumours should be considered. These tumours are notoriously difficult to locate; Ga-DOTATE PET is probably superior to other imaging modalities including FDG-PET in isolating mesenchymal tumours. Disclosures K. Fisher None. S. Melath None. S. Patel None.

Background:Anti-Ku antibodies have been associated with various connective tissue diseases, including myositis, arthritis, interstitial lung disease and glomerulonephritis1.Objectives:We present a case of a woman initially diagnosed with biopsy proven Kikuchi-Fujimoto disease who later developed a rapidly progressive myositis in association with anti-Ku antibodies.Methods:A 47 year-old woman, originally from Myanmar, presented with lymphadenopathy, myalgia, fatigue, livedo reticularis and low-grade fever for the previous 6 months. This was initially diagnosed as a viral infection. Her myalgia progressed with proximal muscle weakness in both legs and associated rise in creatine kinase levels to 349U/L (normal range 25-200). She also developed dyspnoea, an erythematous rash, mouth ulcers and unintentional weight loss.Blood tests show a lymphopenia and progressively rising CK, with a maximum level of 516 U/L. MRI whole body confirmed a widespread diffuse myositis in her upper and lower limbs, with an unusual ‘speckled’ pattern. High resolution CT Chest was normal. C3 0.40 g/l (normal range 0.75-1.65) and C4 0.12 g/l (0.14-0.54) were low, with a positive ANA (1:160) and Ro-60 antibody. dsDNA, antiphospholipid screen and virology screens were all negative. Extended myositis panel revealed positive anti-Ku antibodies. Axillary lymph node biopsy confirmed necrotising lymphadenitis, consistent with Kikuchi-Fujimoto disease.Results:She was initially treated with low dose Prednisolone and Hydroxychloroquine, with a limited response. Due to progressive myositis, pulsed IV Methylprednisolone 1g was provided over 3 days and mycophenolate mofetil (MMF) was started.An inpatient stay was needed after developing an axillary node abscess and a chest infection. This was treated with intravenous antibiotics and repeated aspirations. Due to progressive myositis on a background of sepsis, intravenous immunoglobulin (IVIG) was administered over 5 days. Our patient made a good recovery, with normalization of CK levels and resolution of the myositis noted on repeat MRI scan. She remains on MMF as maintenance therapy.Conclusion:Anti Ku antibodies appear to be associated with 2 spectrums of disease – elevated CK levels with interstitial lung disease and renal disease associated with anti-dsDNA antibodies1To our knowledge this is the first report in association with Kikuchi-Fujimoto disease. The combination of MMF and IVIG appears to have been effective treatment and her renal function remains stable, although we are monitoring the patient carefully for the possible development of interstitial lung disease.References:[1]Spielmann L, Nespola B, Séverac F, et al. Anti-Ku syndrome with elevated CK and anti-Ku syndrome with anti-dsDNA are two distinct entities with different outcomes. Annals of the Rheumatic Diseases 2019;78:1101-1106.Disclosure of Interests:None declared

Background Rheumatoid arthritis (RA) treatment is target driven. The aim is to prevent joint damage and relieve pain and functional loss. X-ray (XR) erosions are an unambiguous sign of disease activity and progression. Objectives We aimed to review our practice in looking for erosions in our biologic treated patients. We chose this group as they were likely to have the most severe and clearly defined RA. Methods 100 random biologic treated patients from our biologics database were selected for analysis. We used patient letters and our digital imaging system (PACS) for further information. Our PACS has records running back to 2004. Results Mean age was 58 years. 77% were female. Mean duration of RA was 10.6 years (range 0.9–44 years). 46 were currently receiving etanercept; 17 tocilizumab; 15 adalimumab; 14 certolizumab; 5 rituximab and 3 abatacept. 61 patients were current prednisolone users. The mean duration of biologic treatment was 4.8 years. 44 patients had received more than one biologic drug; 17 more than two. Mean DAS was 3.4. 72 patients had had previous documented hand XRs; 25 (34%) of these had erosions. The mean duration since the last hand XR was 37 months. 27 patients had had 2 previous hand XRs; 11 had had 3, 4 had had 4 and 2 had had 6 previous XRs. In 19 cases hand erosions appeared to have progressed in the patients who had had more than one XR. 44 patients had had previous foot XRs; 15 (34%) had erosions. 26 patients had had more than one foot XR. 36 patients had had previous joint ultrasound (US); in 17 (47%) US suggested active synovitis. The mean duration since the last US was 17 months. Conclusions Our patients had relatively high disease activity despite biologic treatment, over half were also on steroids and significant numbers had had several biologic switches. Despite this only around two thirds of patients had had previous hand XRs documented over an average of 10 years RA duration, and there was a long average time since the last imaging. US rates were lower, but scans were more recent, perhaps suggesting a more modern trend to US over XR. Less than half of patients had had foot XRs. Although there was a lower rate of foot XRs the rate of erosions was similar in hand and foot XRs, suggesting similar patterns of joint damage. Interestingly, despite erosions being a hard end point in most treatment trials, NICE guidance only suggests XR early in RA in ‘people with persistent synovitis’1 and EULAR guidance suggests assessing for ‘structural damage’ without specifying time intervals.2 Although newer imaging techniques may be more sensitive, XRs remain cheap, quickly accessible and allow objective assessment, particularly in long term patients being assessed for biologic switches. Our audit suggests that this well established and useful measure of disease burden may currently be relatively neglected. References [1] https://www.nice.org.uk/guidance/qs33 [2] http://ard.bmj.com/content/early/2017/03/17/annrheumdis-2016-210715 Disclosure of Interest None declared

L-type voltage gated calcium channels play essential role in contraction of various skeletal and vascular smooth muscles, thereby plays important role in regulating blood pressure. Dihydropyridine receptors have been targeted for development of newer antihypertensive agents, one of the structurally analogs nucleus dihydropyrimidines have been reported earlier by us as a potential agent toward development of calcium channel modulator. A pre-synthetic QSAR was run and on the basis of structure activity relationship a series of twenty three molecules was synthesized and studied by myosin light chain kinase assay (MLCK), Angiotensin Converting Enzyme (ACE) colorimetric assay, non-invasive blood pressure (NIBP) and invasive blood pressure (IBP) methods. Molecules with significant efficacy were studied for their single crystal X-ray diffraction, molecular docking, molecular dynamics and post-synthetic QSAR. The NIBP and IBP methods screened molecules with better percentage inhibition versus time compared to standard drug Nifedipine. The lead compound ethyl 2-methyl-4-(3-nitrophenyl)-4H-pyrimido [2,1-b] [1,3] benzothiazole-3-carboxylate (26) presented a triclinic structure with polymeric chain packing in lattice. 26 exhibited IC50 on MLCK assay of 2.1±1.7 μM with selectivity of L-type calcium channels and comparative to Nifedipine. It offered satisfactory physicochemical properties with partition coefficient of (ClogP) 4.64. Its pharmacokinetic profile is also good with Cmax at 0.40 μg/ml by oral route with Tmax reaching in 0.5 h which means in 30 min. 26 also exhibits superior t1/2 of 5.4 h and oral bioavailability of (F) 56.75% with an AUC0-∞ of 0.84 μg h/ml. Molecular docking studies indicates toward the interaction of lead compound via hydrogen bonds with Lys144, Glu181 and Asp183, it forms the Van der Walls interactions with Ser18, Asp20, Asn187, Pro185, Glu180, Glu181 and Arg10 with Glide score and Glide energy to be -3.602 and -47.098, respectively. Post-synthetic QSAR of newly synthesized molecules indicates toward improvement with respect to steric descriptor which contributed negatively in former series.

Background: Interferon regulatory factor 6 (IRF6) is a transcription factor with distinct and conserved DNA and protein binding domains. Mutations within the protein binding domain have been significantly observed in subjects with orofacial cleft relative to healthy controls. In addition, recent studies have identified loss of expression of IRF6 due to promoter hypermethylation in cutaneous squamous cell carcinomas. Since mutational events occurring within the conserved domains are likely to affect the function of a protein, we investigated whether regions within the IRF6 gene that encodes for the conserved protein binding domain carried mutations in oral squamous cell carcinoma (OSCC). Materials and Methods: Total chromosomal DNA extracted from 32 post surgical OSCC tissue samples were amplified using intronic primers flanking the exon 7 of IRF6 gene, which encodes for the major region of protein binding domain. The PCR amplicons from all the samples were subsequently resolved in a 1.2% agarose gel, purified and subjected to direct sequencing to screen for mutations. Results: Sequencing analysis resulted in the identification of a mutation within exon 7 of IRF6 that occurred in heterozygous condition in 9% (3/32) of OSCC samples. The wild type codon TTC at position 252 coding for phenylalanine was found to be mutated to TAC that coded for tyrosine (F252Y). Conclusions: The present study identified for the first time a novel mutation within the conserved protein binding domain of IRF6 gene in tissue samples of subjects with OSCC.

A 35-year-old Afro-Caribbean woman presented with dyspnoea, urticarial rash and myalgia 1 month after treatment for a community-acquired respiratory tract infection. Investigations revealed raised antisynthetase antibodies, lung fibrosis and an inflammatory myopathy. The patient was diagnosed with antisynthetase syndrome (ASS) and started on immunosuppressive medication. Despite treatment she died 4 weeks after presentation from a fulminant cardiomyopathy. ASS is a rare condition and is not typically associated with a cardiomyopathy. This case report intends to raise awareness that cardiomyopathy is a potentially fatal complication of ASS.

Association between cold stress and oxidative stress was demonstrated by measuring the activity of two antioxidant enzymes and the level of free radicals generated in two batches of cells of an Antarctic bacterium Pseudomonas fluorescens MTCC 667, grown at 22 and 4°C. Increase in oxidative stress in cells grown at low temperature was evidenced by increase in the activity of an enzyme and also in the amount of free radicals generated, in the cold-grown cells. The association between cold stress and oxidative stress demonstrated in this investigation bolsters the concept of interlinked stress response in bacteria.

Patients with rheumatic disorders treated with TNF inhibitors are at increased risk of developing TB. There is no 'gold-standard' for the diagnosis of latent TB prior to initiation of biologic agents. We report our own experience of comparing two interferon gamma release assays (IGRAs) in screening for latent TB in a 'high-risk' TB area in patients with rheumatic disorders. The study demonstrated good concordance between the two tests. We believe the additional cost of these assays is justified in high-risk populations prior to biologic agents, with 16% of the current study population with at least one positive IGRA assay.