LLL 44-1 Micronutrients in clinical nutrition: Trace elements.

BACKGROUND: Trace elements are an essential component of metabolism and medical nutrition therapy, with key roles in metabolic pathways, antioxidation, and immunity, which the present course aims at summarizing. RESULTS: Medical nutrition therapy includes the provision of all essential trace elements. The clinical essential issues are summarized for Copper, Iron, Selenium, Zinc, Iodine, Chromium, Molybdenum, and Manganese: the optimal analytical techniques are presented. The delivery of all these elements occurs nearly automatically when the patient is fed with enteral nutrition, but always requires separate prescription in case of parenteral nutrition. Isolated deficiencies may occur, and some patients have increased requirements, therefore a regular monitoring is required. The clinicians should always consider the impact of inflammation on blood levels, mostly lowering them even in absence of deficiency. CONCLUSION: This text summarises the most relevant clinical manifestations of trace element depletion and deficiency, the difficulties in assessing status, and makes practical recommendations for provision for enteral and parenteral nutrition.

THE ROLE OF INTRAVITREAL METHOTREXATE AS AN ADJUNCT TO LOCAL OR SYSTEMIC CORTICOSTEROIDS IN VITRECTOMY FOR RHEGMATOGENOUS RETINAL DETACHMENT AND CHOROIDAL DETACHMENT: A Pilot Study.

PURPOSE: To evaluate the role of repeated intravitreal methotrexate as an adjunct to pars plana vitrectomy in the management of rhegmatogenous retinal detachment with choroidal detachment. METHOD: The authors compared anatomical and visual outcomes of rhegmatogenous retinal detachment with choroidal detachment eyes that underwent pars plana vitrectomy with (Group B) or without repeated intravitreal methotrexate (Group A). RESULTS: The study included 25 eyes of 25 patients, 16 eyes in Group A and nine in Group B. Both groups had similar baseline characteristics. In Group A, successful retinal attachment was achieved in 50% as compared with 89% in Group B; however, the difference was not statistically significant ( P = 0.08). Also, Group B had a significantly greater change in visual acuity from baseline to the last follow-up visit (1.6 + 1.5 logMAR units) compared with Group A (1.18 + 1 logMAR units) ( P = 0.05). There were no significant safety concerns with the use of intravitreal methotrexate. CONCLUSION: Repeated intravitreal methotrexate after vitrectomy for rhegmatogenous retinal detachment with choroidal detachment improves outcomes without posing major safety concerns. Nonetheless, further investigation is necessary to establish the optimal intravitreal methotrexate dosage and duration to prevent recurrence effectively.

The science of micronutrients in clinical practice - Report on the ESPEN symposium.

BACKGROUND & AIMS: The European Society for Clinical Nutrition and Metabolism published its first clinical guidelines for use of micronutrients (MNs) in 2022. A two-day web symposium was organized in November 2022 discussing how to apply the guidelines in clinical practice. The present paper reports the main findings of this symposium. METHODS: Current evidence was discussed, the first day being devoted to clarifying the biology underlying the guidelines, especially regarding the definition of deficiency, the impact of inflammation, and the roles in antioxidant defences and immunity. The second day focused on clinical situations with high prevalence of MN depletion and deficiency. RESULTS: The importance of the determination of MN status in patients at risk and diagnosis of deficiencies is still insufficiently perceived, considering the essential role of MNs in immune and antioxidant defences. Epidemiological data show that deficiencies of several MNs (iron, iodine, vitamin D) are a global problem that affects human health and well-being including immune responses such as to vaccination. Clinical conditions frequently associated with MN deficiencies were discussed including cancer, obesity with impact of bariatric surgery, diseases of the gastrointestinal tract, critical illness, and aging. In all these conditions, MN deficiency is associated with worsening of outcomes. The recurrent problem of shortage of MN products, but also lack of individual MN-products is a worldwide problem. CONCLUSION: Despite important progress in epidemiology and clinical nutrition, numerous gaps in practice persist. MN depletion and deficiency are frequently insufficiently searched for in clinical conditions, leading to inadequate treatment. The symposium concluded that more research and continued education are required to improve patient outcome.

Fenfluramine in the treatment of Dravet syndrome: Results of a third randomized, placebo-controlled clinical trial.

OBJECTIVE: This study was undertaken to assess the safety and efficacy of fenfluramine in the treatment of convulsive seizures in patients with Dravet syndrome. METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial enrolled patients with Dravet syndrome, aged 2-18 years with poorly controlled convulsive seizures, provided they were not also receiving stiripentol. Eligible patients who had ≥6 convulsive seizures during the 6-week baseline period were randomized to placebo, fenfluramine .2 mg/kg/day, or fenfluramine .7 mg/kg/day (1:1:1 ratio) administered orally (maximum dose = 26 mg/day). Doses were titrated over 2 weeks and maintained for an additional 12 weeks. The primary endpoint was a comparison of the monthly convulsive seizure frequency (MCSF) during baseline and during the combined titration-maintenance period in patients given fenfluramine .7 mg/kg/day versus patients given placebo. RESULTS: A total of 169 patients were screened, and 143 were randomized to treatment. Mean age was 9.3 ± 4.7 years (±SD), 51% were male, and median baseline MCSF in the three groups ranged 12.7-18.0 per 28 days. Patients treated with fenfluramine .7 mg/kg/day demonstrated a 64.8% (95% confidence interval = 51.8%-74.2%) greater reduction in MCSF compared with placebo (p < .0001). Following fenfluramine .7 mg/kg/day, 72.9% of patients had a ≥50% reduction in MCSF compared with 6.3% in the placebo group (p < .0001). The median longest seizure-free interval was 30 days in the fenfluramine .7 mg/kg/day group compared with 10 days in the placebo group (p < .0001). The most common adverse events (>15% in any group) were decreased appetite, somnolence, pyrexia, and decreased blood glucose. All occurred in higher frequency in fenfluramine groups than placebo. No evidence of valvular heart disease or pulmonary artery hypertension was detected. SIGNIFICANCE: The results of this third phase 3 clinical trial provide further evidence of the magnitude and durability of the antiseizure response of fenfluramine in children with Dravet syndrome.

The relationship between micronutrient status, frailty, systemic inflammation, and clinical outcomes in patients admitted to hospital with COVID-19.

BACKGROUND: Micronutrients have been associated with disease severity and poorer clinical outcomes in patients with COVID-19. However, there is a paucity of studies examining if the relationship with micronutrient status and clinical outcomes is independent of recognised prognostic factors, specifically frailty and the systemic inflammatory response (SIR). The aim of the present study was to examine the relationship between micronutrient status, frailty, systemic inflammation, and clinical outcomes in patients admitted with COVID-19. METHODS: Retrospective analysis of prospectively collected data was performed on patients with confirmed COVID-19, admitted to hospital between the 1st April 2020-6th July 2020. Clinicopathological characteristics, frailty assessment, biochemical and micronutrient laboratory results were recorded. Frailty status was determined using the Clinical Frailty scale. SIR was determined using serum CRP. Clinical outcomes of interest were oxygen requirement, ITU admission and 30-day mortality. Categorical variables were analysed using chi-square test and binary logistics regression analysis. Continuous variables were analysed using the Mann-Whitney U or Kruskal Wallis tests. RESULTS: 281 patients were included. 55% (n = 155) were aged ≥ 70 years and 39% (n = 109) were male. 49% (n = 138) of patients were frail (CFS > 3). 86% (n = 242) of patients had a serum CRP > 10 mg/L. On univariate analysis, frailty was significantly associated with thirty-day mortality (p < 0.001). On univariate analysis, serum CRP was found to be significantly associated with an oxygen requirement on admission in non-frail patients (p = 0.004). Over a third (36%) of non-frail patients had a low vitamin B1, despite having normal reference range values of red cell B2, B6 and selenium. Furthermore, serum CRP was found to be significantly associated with a lower median red cell vitamin B1 (p = 0.029). CONCLUSION: Vitamin B1 stores may be depleted in COVID-19 patients experiencing a significant SIR and providing rationale for thiamine supplementation. Further longitudinal studies are warranted to delineate the trend in thiamine status following COVID-19.

IMMEDIATE VITRECTOMY vs TAP AND INJECT IN EYES WITH ACUTE POSTCATARACT ENDOPHTHALMITIS AND VISUAL ACUITY ≥HM: A Randomized Clinical Trial.

PURPOSE: To compare the outcomes of immediate pars plana vitrectomy (PPV) and tap and inject in eyes with postcataract surgery endophthalmitis. METHODS: Patients presenting with acute postcataract surgery endophthalmitis and visual acuity between ≥ hand movement and <6/18 were randomized to receive either PPV (Group A) or tap and inject (Group B). RESULTS: There were 26 and 31 eyes in Group A and Group B, respectively. The final mean visual acuity at 6 weeks [0.14 (Snellen equivalent 6/7.5) versus 0.22 (Snellen equivalent 6/9.5) LogMAR in Groups A and B, respectively; P = 0.2] was similar. However, eyes in Group A had significantly greater mean letter gain in vision compared with Group B (66.36 vs. 43.36, P = 0.02), and more eyes in Group A (88%) than in Group B (65%) attained a visual acuity of ≥ 6/18 ( P = 0.06). Eyes in Group B needed more reinterventions including delayed vitrectomy after tap and inject than those in Group A (39% vs. 8%; P = 0.09). On subgroup analysis, the mean visual acuity at the final follow-up was significantly better in the immediate PPV group compared with the delayed PPV group ( P = 0.04). CONCLUSION: PPV resulted in earlier recovery, lesser interventions, and greater change in visual acuity than tap and inject in eyes with postcataract surgery endophthalmitis presenting with visual acuity of ≥HM.

Pitfalls in the interpretation of blood tests used to assess and monitor micronutrient nutrition status.

Assessment of micronutrient (MN) status is of particular importance in patients who require medical nutrition therapy, especially those requiring parenteral nutrition. Blood testing is generally the only tool available in clinical settings to assess MN status. However, using plasma or serum concentration faces pitfalls mainly because of the impact of inflammation that diverts the MNs from the circulating compartment. This review aims to review the blood tests that are useful and provide information about how to integrate functional markers of status to reach a clinically relevant diagnosis. Most impacted, with a significant and proportional decrease in plasma concentrations, are iron, selenium, zinc, thiamin, folic acid, cobalamin, and vitamins A, C, and D; copper is the only MN for which the plasma concentration increases. Therefore, a surrogate marker of inflammation, C-reactive protein, must always be determined simultaneously. Validated intracellular and functional tests are proposed to improve status assessment. A protocol is suggested for tests required both on commencing and during nutrition support. A timely turnaround of analysis is essential for results to be clinically useful. In some cases, the appropriate provision of MNs should be commenced before results have been obtained to confirm the clinical assessment. Laboratory tests of MN status are an area prone to misuse and misinterpretation. The appropriate use and interpretation of such tests are essential to ensure the correct management of nutrition problems.

A New Mechanism of Silicone Oil-Induced Glaucoma and Its Management.

Purpose: To describe a case of secondary acute angle closure glaucoma due to silicone oil migration into the posterior chamber causing entrapment of aqueous and its successful management. Case Presentation. A 69-year-old female presented with decreased vision and pain in the left eye (LE) for one month. She had a history of complicated phacoemulsification with nucleus drop and retinal detachment in LE, for which vitreoretinal surgery with silicone oil endotamponade was done. She was also a known case of primary open angle glaucoma on medications. The corrected distance visual acuity was 20/20 and 20/125 in the right eye (RE) and LE, respectively. The intraocular pressure (IOP) was 18 mmHg in RE and 45 mmHg in LE. Anterior segment examination of LE revealed 270° of iridocorneal apposition in the periphery of the anterior chamber. Fundus examination of LE showed silicone oil filled vitreous cavity with attached retina. Given the recent history of silicone oil injection and elevated IOP despite maximum antiglaucoma medications, we decided to perform laser peripheral iridotomy (LPI) in the area of iridocorneal apposition. Following LPI, the IOP in LE came down to 17 mmHg and remained stable within the normal range for one month, after which the patient was taken up for silicone oil removal. Conclusion: This case report highlights a new mechanism of silicone oil-induced glaucoma and the technique of performing LPI in the area of iridocorneal apposition, for the first time in the literature. Silicone oil migration into the posterior chamber from the vitreous cavity in the presence of zonular dehiscence can push the iris forward and lead to iridocorneal apposition, resulting in an acute rise in IOP. Performing LPI within the area of iridocorneal apposition can help the aqueous seep into the anterior chamber and release the silicone oil globule trapped behind the iris to enter the anterior chamber, thus relieving the iridocorneal adhesions and lowering the IOP.

Randomised trial of intravenous thiamine and/or magnesium sulphate administration on erythrocyte transketolase activity, lactate concentrations and alcohol withdrawal scores.

Alcohol withdrawal syndrome (AWS) occurs in 2% of patients admitted to U.K. hospitals. Routine treatment includes thiamine and benzodiazepines. Laboratory studies indicate that thiamine requires magnesium for optimal activity, however this has not translated into clinical practice. Patients experiencing AWS were randomized to three groups: (group 1) thiamine, (group 2) thiamine plus MgSO4 or (group 3) MgSO4. Pre- and 2-h post-treatment blood samples were taken. AWS severity was recorded using the Glasgow Modified Alcohol Withdrawal Score (GMAWS). The primary outcome measure was 15% change in erythrocyte transketolase activity (ETKA) in group 3. Secondary outcome measures were change in plasma lactate concentrations and time to GMAWS = 0. 127 patients were recruited, 115 patients were included in the intention-to-treat analysis. Pre-treatment, the majority of patients had normal or high erythrocyte thiamine diphosphate (TDP) concentrations (≥ 275-675/> 675 ng/gHb respectively) (99%), low serum magnesium concentrations (< 0.75 mmol/L) (59%), and high plasma lactate concentrations (> 2 mmol/L) (67%). Basal ETKA did not change significantly in groups 1, 2 or 3. Magnesium deficient patients (< 0.75 mmol/L) demonstrated less correlation between pre-treatment basal ETKA and TDP concentrations than normomagnesemic patients (R2 = 0.053 and R2 = 0.236). Median plasma lactate concentrations normalized (≤ 2.0 mmol/L) across all three groups (p < 0.001 for all groups), but not among magnesium deficient patients in group 1 (n = 22). The median time to achieve GMAWS = 0 for groups 1, 2 and 3 was 10, 5.5 and 6 h respectively (p < 0.001). No significant difference was found between groups for the primary endpoint of change in ETKA. Co-administration of thiamine and magnesium resulted in more consistent normalization of plasma lactate concentrations and reduced duration to achieve initial resolution of AWS symptoms.ClinicalTrials.gov: NCT03466528.

Safety and efficacy of suprachoroidal triamcinolone acetonide for the management of serous choroidal detachment prior to rhegmatogenous retinal detachment surgery: A Pilot study.

Purpose: To study the safety and efficacy of pre-operative suprachoroidal triamcinolone acetonide (SCTA) for achieving reduction/resolution of serous choroidal detachment (CD) associated with rhegmatogenous retinal detachment (RRD). Methods: This was a prospective, noncomparative, interventional pilot study. All consecutive patients presenting with RD and coexisting CD underwent transconjunctival injection of SCTA before proceeding with vitrectomy/scleral buckle surgery. Sequential ultrasound B scans were performed for assessing the change in height of the CD. Results: The mean age of the cohort was 53.8 ± 10.8 years (range: 39-72 years). The CD was present in a median of 3 quadrants; the cumulative mean CD height was 5.59 mm (range: 2.02-9.42 mm). Following SCTA, a successful response (>50% reduction) was seen in five eyes by day 3 and in two eyes by day 5. Three eyes failed to respond to SCTA and required surgical drainage before proceeding with vitrectomy. No intraprocedural injection-related complications were noted. A transient rise in the intraocular pressure (30 mmHg) was seen in one eye following vitrectomy and was managed successfully with topical antiglaucoma medications. Conclusion: Suprachoroidal administration of triamcinolone appears to be a safe and effective technique to achieve CD resolution in eyes with RRD.

Development of age-dependent micronutrient centile charts and their utility in children with chronic gastrointestinal conditions at risk of deficiencies: A proof-of-concept study.

BACKGROUND & AIMS: Interpretation of blood micronutrient levels requires age-appropriate reference intervals. This study developed age-dependent micronutrient centiles for healthy children (HC) and explored their utility in sick children. METHODS: 244 blood samples were collected from normal HC who underwent tests for acute illness. Age-dependent, centile charts were fitted for zinc, copper, magnesium and selenium in plasma and erythrocytes (RBC), and for vitamins B1, B2 and B6 in RBC. For 34 children with Crohn's disease (CrD) and 55 with coeliac disease (CoeD), Z-scores for the levels of these micronutrients were computed, using the new charts. Associations were explored between plasma and RBC micronutrient Z-scores, and in CrD with CRP and serum albumin. RESULTS: In HC, plasma zinc and selenium increased and plasma copper, magnesium and RBC vitamins B1, B2 and B6 decreased with age. In HC and in CrD, plasma and RBC Z-scores for copper, selenium and magnesium (all p < 0.001) were positively correlated, but not for zinc. In CrD, albumin was related with plasma zinc (rho = 0.62; p < 0.001) and selenium Z-scores (rho = 0.65; p < 0.001) and plasma copper Z-score with CRP (rho = 0.45; p = 0.02). A higher proportion of CrD children had low levels for B2 (21% vs 0%; p = 0.01) and B6 (18% vs 0%; p = 0.02) using the new centile charts than the local laboratory references. CONCLUSION: Age-dependent micronutrient centile charts enable tracking of micronutrient status, Z-score calculation and may prevent misdiagnosis and inappropriate treatment of deficiencies. In systemic inflammatory conditions, RBC measurements of certain micronutrients may be more reliable to use than measurements in plasma.

All India Ophthalmological Society (AIOS) Task Force guidelines to prevent intraocular infections and cluster outbreaks after cataract surgery.

Infectious endophthalmitis is a serious and vision-threatening complication of commonly performed intraocular surgeries such as cataract surgery. The occurrence of endophthalmitis can result in severe damage to the uveal and other ocular tissues even among patients undergoing an uncomplicated surgical procedure. If the infections result from common factors such as surgical supplies, operative or operation theater-related risks, there can be a cluster outbreak of toxic anterior segment syndrome (TASS) or infectious endophthalmitis, leading to several patients having an undesirable outcome. Since prevention of intraocular infections is of paramount importance to ophthalmic surgeons, the All India Ophthalmological Society (AIOS) has taken the lead in the formation of a National Task Force to help ophthalmic surgeons apply certain universal precautions in their clinical practice. The Task Force has prepared a handy checklist and evidence-based guidelines to minimize the risk of infectious endophthalmitis following cataract surgery.

SCN8A Epilepsy, Developmental Encephalopathy, and Related Disorders.

Understanding the precise genetic -basis of disease is one of the critical developments in medicine in the twenty-first century. Genetic testing has revolutionized the diagnosis and treatment of neurological diseases in children. Whole-genome and whole-exome sequencing have particularly been useful in understanding the genetic basis of childhood epileptic encephalopathies characterized by early-onset seizures with significant developmental impairment and regression. In this review we describe the identification of a new epileptic encephalopathy caused by a de novo mutation in the SCN8A gene, which encodes for NaV1.6, a vital sodium channel in the central nervous system. SCN8A variants in patients with epilepsy result primarily in gain-of-function in Nav1.6 and hyperexcitability of neurons in the central nervous system. Following the original discovery in 2012 of a de novo mutation in a child with developmental and epileptic encephalopathy (DEE), more than 400 individuals with SCN8A-related disorders have been identified. Clinical manifestations range from movement disorders or intellectual disability only to severe DEE, which includes epileptic encephalopathy with intractable multivariate seizure types, developmental impairment and regression, intellectual disability, and other neurological manifestations. Gain-of-function of the Nav1.6 channel predicts effectiveness of sodium channel-blocking agents in the treatment of seizures, which has been corroborated by clinical experience. Nevertheless, treatment options remain limited and adverse effects are common. However, with the availability of a growing database of genetic and clinical data along with transfected cell lines and mouse models, more efficacious, targeted, and selective treatments may soon be feasible.

The relation between acute changes in the systemic inflammatory response and circulating thiamine and magnesium concentrations after elective knee arthroplasty.

Thiamine diphosphate (TDP) and magnesium are co-factors for key enzymes in human intermediary metabolism. However, their role in the systemic inflammatory response (SIR) is not clear. Therefore, the aim of the present study was to examine the relation between acute changes in the SIR and thiamine and magnesium dependent enzyme activity in patients undergoing elective knee arthroplasty (a standard reproducible surgical injury in apparently healthy individuals). Patients (n = 35) who underwent elective total knee arthroplasty had venous blood samples collected pre- and post-operatively for 3 days, for measurement of whole blood TDP, serum and erythrocyte magnesium, erythrocyte transketolase activity (ETKA), lactate dehydrogenase (LDH), glucose and lactate concentrations. Pre-operatively, TDP concentrations, erythrocyte magnesium concentrations, ETKA and plasma glucose were within normal limits for all patients. In contrast, 5 patients (14%) had low serum magnesium concentrations (< 0.75 mmol/L). On post-operative day1, both TDP concentrations (p < 0.001) and basal ETKA (p < 0.05) increased and serum magnesium concentrations decreased (p < 0.001). Erythrocyte magnesium concentrations correlated with serum magnesium concentrations (rs = 0.338, p < 0.05) and remained constant during SIR. Post-operatively 14 patients (40%) had low serum magnesium concentrations. On day1 serum magnesium concentrations were directly associated with LDH (p < 0.05), WCC (p < 0.05) and neutrophils (p < 0.01). Whole blood TDP and basal ETKA increased while serum magnesium concentrations decreased, indicating increased requirement for thiamine and magnesium dependent enzyme activity during SIR. Therefore, thiamine and magnesium represent potentially modifiable therapeutic targets that may modulate the host inflammatory response. Erythrocyte magnesium concentrations are likely to be reliable measures of status, whereas serum magnesium concentrations and whole blood TDP may not.ClinicalTrials.gov: NCT03554668.

The systemic inflammatory response and clinicopathological characteristics in patients admitted to hospital with COVID-19 infection: Comparison of 2 consecutive cohorts.

BACKGROUND: In order to manage the COVID-19 systemic inflammatory response, it is important to identify clinicopathological characteristics across multiple cohorts. METHODS: The aim of the present study was to compare the 4C mortality score, other measures of the systemic inflammatory response and clinicopathological characteristics in two consecutive cohorts of patients on admission with COVID-19. Electronic patient records for 2 consecutive cohorts of patients admitted to two urban teaching hospitals with COVID-19 during two 7-week periods of the COVID-19 pandemic in Glasgow, U.K. (cohort 1: 17/3/2020-1/5/2020) and (cohort 2: 18/5/2020-6/7/2020) were examined for routine clinical, laboratory and clinical outcome data. RESULTS: Compared with cohort 1, cohort 2 were older (p<0.001), more likely to be female (p<0.05) and have less independent living circumstances (p<0.001). More patients in cohort 2 were PCR positive, CXR negative (both p<0.001) and had low serum albumin concentrations (p<0.001). 30-day mortality was similar between both cohorts (23% and 22%). In cohort 2, age >70 (p<0.05), male gender (p<0.05), COPD (p<0.05), cognitive impairment (p<0.05), frailty (p<0.001), delirium (p = 0.001), CRP>150mg/L (p<0.05), albumin <30 g/L (p<0.01), elevated perioperative Glasgow Prognostic Score (p<0.05), elevated neutrophil-lymphocyte ratio (p<0.001), low haematocrit (p<0.01), elevated PT (p<0.05), sodium <133 mmol/L (p<0.01) elevated urea (p<0.001), creatinine (p<0.001), glucose (p<0.05) and lactate (p<0.001) and the 4C score (p<0.001) were associated with 30-day mortality. In multivariate analysis, greater frailty (CFS>3) (OR 11.3, 95% C.I. 2.3-96.7, p<0.05), low albumin (<30g/L) (OR 2.5, 95% C.I. 1.0-6.2, p<0.05), high NLR (≥3) (OR 2.2, 95% C.I. 1.5-4.5, p<0.05) and the 4C score (OR 2.4, 95% C.I. 1.0-5.6, p<0.05) remained independently associated with 30-day mortality. CONCLUSION: In addition to the 4C mortality score, frailty score and a low albumin were strongly independently associated with 30-day mortality in two consecutive cohorts of patients admitted to hospital with COVID-19. TRIAL REGISTRATION: clinicaltrials.gov: NCT04484545.

Micronutrient deficiencies in children with coeliac disease; a double-edged sword of both untreated disease and treatment with gluten-free diet.

INTRODUCTION: In coeliac disease (CD) micronutrient deficiencies may occur due to malabsorption in active disease and diminished intake during treatment with a gluten-free diet (GFD). This study assessed the micronutrient status in children with CD at diagnosis and follow-up. METHODS: Fifteen micronutrients were analysed in 106 blood samples from newly diagnosed CD and from patients on a GFD for <6 months, 6-12 months and with longstanding disease (>12 months). Predictors of micronutrient status included: demographics, disease duration, anthropometry, gastrointestinal symptoms, raised tissue transglutaminase antibodies (TGA), multivitamin use and faecal gluten immunogenic peptide (GIP). Micronutrient levels were compared against laboratory reference values. RESULTS: At CD diagnosis (n = 25), low levels in ≥10% of patients were observed for: vitamins E (88%), B1 (71%), D (24%), K (21%), A (20%) and B6 (12%), ferritin (79%), and zinc (33%). One year post-diagnosis, repletion of vitamins E, K, B6 and B1 was observed (<10% patients). In contrast, deficiencies for vitamins D, A and zinc did not change significantly post-diagnosis. Copper, selenium and magnesium did not differ significantly between diagnosis and follow-up. All samples for B2, folate, vitamin C (except for one sample) and B12 were normal. A raised TGA at follow-up was associated with low vitamins A and B1 (raised vs normal TGA; vitamin A: 40% vs 17%, p = 0.044, vitamin B1: 37% vs 13%, p = 0.028). Low vitamin A (p = 0.009) and vitamin D (p = 0.001) were more common in samples collected during winter. There were no associations between micronutrient status with GIP, body mass index, height, socioeconomic status, or gastrointestinal symptom. Multivitamin use was less common in patients with low vitamin D. CONCLUSIONS: Several micronutrient deficiencies in CD respond to a GFD but others need to be monitored long-term and supplemented where indicated.

Clinical efficacy and safety of Razumab® (CESAR) study: Our experience with the world's first biosimilar Ranibizumab.

Purpose: : The aim of this study was to evaluate the efficacy and safety of Razumab (the biosimilar Ranibizumab by Intas Pharmaceuticals Ltd.) for the treatment of chorioretinal vascular diseases such as diabetic macular edema (DME), choroidal neovascular membrane (CNVM), and macular edema secondary to retinal vein occlusion (RVO). Methods: : We conducted a single-center, retrospective study, including patients with DME, CNVM, and RVO, who had received treatment with Razumab® between October 2018 and September 2019. Primary outcome measures were the changes in corrected distance visual acuity (CDVA) and central foveal thickness (CFT) from baseline to 1 month and 3 months. Secondary outcome measures included intraocular pressure (IOP) at day 1, any signs of ocular inflammation or systemic adverse events during the follow-up. Results: : One hundred and fifty-three eyes of 141 patients were analyzed. The indications included DME in 70 (45.8%) eyes, CNVM in 70 (45.8%) eyes, and RVO in 13 (8.4%) eyes. Mean CDVA improved from baseline (0.62 ± 0.44) to month 1 (0.45 ± 0.42) and maintained till 3 months (0.42 ± 0.44; P < 0.001). Mean CFT showed significant reduction from baseline (405.68 ± 192.422 µm) to month 1 (286.08 ± 118.36 µm) and month 3 (271 ± 104.24 µm; P < 0.001). None of the eyes recorded IOP >20 mmHg on day 1. No evidence of ocular toxicity or systemic adverse event was noted. Conclusion: : Razumab® showed a rapid improvement in CDVA and CFT in most of the eyes with efficacy observed as early as 1 month and maintained till 3 months. The biosimilar Ranibizumab can be a safe and effective low-cost drug for treating macular diseases.