Prevalence, Predictors, and Prognosis of Serious Infections in Takayasu Arteritis: A Cohort Study.

OBJECTIVE: To describe the incidence, risk factors, and outcomes associated with serious infections in patients with Takayasu arteritis (TA). METHODS: Serious infections, defined as infections resulting in hospitalization or death or unusual infections like tuberculosis, were identified from a cohort of patients with TA. Corticosteroid and disease-modifying antirheumatic drug (DMARD) use at the time of serious infection was noted. Demographic characteristics, clinical presentation, angiography, and disease activity at presentation, and the use of DMARDs during follow-up were compared between patients with TA with or without serious infections. Mortality in patients with TA who developed serious infections was compared to those who did not using hazard ratios (HR; with 95% CI). RESULTS: Of 238 patients with TA, 38 (16%) had developed serious infections (50 episodes, multiple episodes in 8; 3 episodes resulted in death). Among the 38 initial episodes, 11/38 occurred in those not on corticosteroids and 14/38 in those not on DMARDs. Pneumonia (n = 19) was the most common infection, followed by tuberculosis (n = 12). Patients with TA who developed serious infections vs those who did not had higher disease activity at presentation (active disease 97.4% vs 69.5%, mean Indian Takayasu Arteritis Activity Score 2010 12.7 (SD 7.3) vs 10.2 (SD 7.0), mean Disease Extent Index in Takayasu Arteritis 11.2 (SD 6.1) vs 8.8 (SD 6.1) and were more frequently initiated on corticosteroids or DMARDs. HRs calculated using exponential parametric regression survival-time model revealed increased mortality rate in patients with TA who developed serious infections (HR 5.52, 95% CI 1.75-17.39). CONCLUSION: Serious infections, which occurred in the absence of immunosuppressive treatment in approximately one-fifth of patients with TA, were associated with increased mortality in patients with TA.

Increased mortality rate in Takayasu arteritis is largely driven by cardiovascular disease-a cohort study.

OBJECTIVES: To analyze the risk, causes, and predictors of mortality in Takayasu arteritis (TAK). METHODS: Survival was assessed in a cohort of patients with TAK using Kaplan-Meier curves. Age- and sex-standardized mortality ratio (SMR = observed: expected deaths) for TAK were calculated by applying age- and sex-specific mortality rates for the local population to calculate expected deaths. Hazard ratios (HR with 95%CI) for predictors of mortality based on demographic characteristics, presenting features, baseline angiographic involvement, disease activity, number of immunosuppressive medications used, procedures related to TAK, and any serious infection were calculated using Cox regression or exponential parametric regression models. RESULTS: Among 224 patients with TAK (159 females, mean follow-up duration 44.36 months), survival at 1, 2, 5, and 10 years was 97.34%, 96.05%, 93.93%, and 89.23%, respectively. Twelve deaths were observed, most of which were due to cardiovascular disease (heart failure, myocardial infarction, stroke). Mortality risk was significantly higher with TAK (SMR 17.29, 95%CI 8.95-30.11) than the general population. Earlier age at disease onset (HR 0.90, 95%CI 0.83-0.98; or pediatric-onset vs adult-onset disease, HR 5.51, 95%CI 1.57-19.32), higher disease activity scores (ITAS2010: HR 1.15, 95%CI 1.05-1.25, DEI.TAK: HR 1.18, 95%CI 1.08-1.29), any serious infections (HR 5.43, 95%CI 1.72-17.12), heart failure (HR 7.83, 95%CI 2.17-28.16), or coeliac trunk involvement at baseline (HR 4.01, 95%CI 1.26-12.75) were associated with elevated mortality risk. CONCLUSION: Patients with TAK had an elevated risk of mortality as compared with the general population. Cardiovascular disease was the leading cause of death in TAK.

Paediatric-onset Takayasu's arteritis associates with worse survival than adult-onset Takayasu's arteritis. A matched retrospective cohort study.

OBJECTIVES: A subset of Takayasu's arteritis (TAK) begins in the paediatric age group (≤18 years). Differences in prognosis between paediatric-onset and adult-onset TAK are unclear. We compared the differences in the presentation and survival between paediatric-onset and adult-onset TAK in our cohort of TAK. METHODS: From a retrospective cohort of TAK, clinical presentation, angiographic features, treatments received, disease activity, and survival were compared between paediatric-onset and adult-onset TAK. Multivariable-adjusted logistic regression models were used to compute adjusted odds ratio (aOR) with 95% confidence intervals (95%CI) for paediatric-onset vs. adult-onset TAK. Hazard ratios (HR, with 95%CI) for mortality with paediatric-onset vs adult-onset TAK (crude, adjusted for prognostic covariates or differences in presentation) and propensity score-matched survival analyses were estimated. RESULTS: Among 56 paediatric-onset and 135 adult-onset TAK, chest pain (aOR 3.21, 95%CI 1.06-9.74), heart failure (aOR 3.16, 95%CI 1.05-9.53), headache (aOR 2.60, 95%CI 1.01-6.74), ascending aorta (aOR 3.02, 95%CI 1.04-8.80) and left renal artery involvement (aOR 2.45, 95%CI 1.04-5.80) were more frequent in paediatric-onset TAK. Despite similar longitudinal patterns of disease activity and glucocorticoid or disease-modifying antirheumatic drug (DMARD) use, mortality was higher for paediatric-onset TAK (HR, unadjusted 6.13, 95%CI 1.51-24.91; adjusted for prognostic covariates gender, diagnostic delay, baseline disease activity, number of conventional and biologic/targeted synthetic DMARDs used, 4.97, 95%CI 1.20-20.58; adjusted for differences between groups 5.54, 95%CI 1.22-25.09; after propensity-score matching for prognostic covariates, 54 pairs, log-rank p-value 0.026). CONCLUSIONS: Considering the greater mortality risk, greater vigilance is required while managing paediatric-onset TAK.

Comparing Estimated and Measured Glomerular Filtration Rate in Children with Posterior Urethral Valve.

Background: Posterior urethral valve (PUV) is obstructive uropathy that may lead to chronic kidney disease (CKD) and end-stage renal disease (ESRD) in children. Glomerular filtration rate (GFR) measurement remains the gold standard for renal function measurement. However, due to its less availability and cumbersome, it is not commonly used, and GFR is estimated utilizing various endogenous filtration markers. Objective: This study includes pediatric patients with PUV. We aimed to compare the measured GFR (mGFR) with various creatinine-based estimated GFR methods (eGFR). Materials and Methods: A single-center retrospective study included 62 treated cases of PUV, postvalve fulguration. The mGFR measured by 99mTc-diethylenetriaminepentaacetate in vitro method and compared with eight eGFR (Schwartz, Cockcroft-Gault [CG], Counahan-Barratt [CB], CKD Epidemiology Collaboration [CKD-EPI], full-age spectrum [FAS] age, FAS height (FAS Ht), Schwartz-Lyon [SL], and Ht independent). Patients were subdivided into different CKD grades and compared with various eGFR. Discussion: PUV is a common cause of CKD in children and needs special consideration as there is growth retardation associated with it. It decreases creatinine production and thus fallacies in eGFR measurement. There is a requisite to identify and closely monitor the subset of patients with baseline decreased renal function and therefore at risk of developing ESRD. Results: A total of 62 patients were included. Mean age and serum creatinine levels were 8.02 ± 5.53 years and 1.15 ± 0.95 mg/dl (range: 0.4-4.5), respectively. The mean mGFR was 61.6 ± 31.80 mL/min/1.73 m2 and a positive variable correlation was 0.46-0.77 between mGFR and eGFR. Based on mGFR, there were 14 (22.6%), 21 (33.8%), 13 (20.9%), 9 (14.5%), and 5 (8.1%) patients in Grades I-V, respectively. The correct classification of the CKD grades was noted in 25 (40.3%), 16 (25.8%), 32 (51.6%), 16 (25.8%), 25 (40.3%), 27 (43.5%), 26 (41.9%), and 28 (45.2%) patients by Schwartz, CG, CB, CKD-EPI, FAS age, FAS Ht, SL, and Ht-independent equation. The eGFR overestimates GFR at the lower level and underestimates at higher levels. Conclusion: Our results confirm the considerable limitations of various creatinine-based clearance methods for estimating actual GFR. The creatinine clearance-based eGFR should not replace the measurement of the GFR. An initial measure of the mGFR followed by serial follow-up with the eGFR equation may be done. The most accurate eGFR equations are CB for Grade II, SL or Ht independent for Grade III, FAS age for Grade IV, and SL for Grade V CKD.

Functional dyspepsia in children: A study of pathophysiological factors.

BACKGROUND AND AIM: Functional dyspepsia (FD) is common in children, and treatment targeted towards the altered pathophysiology can improve outcome. We evaluated FD children for abnormality of gastric accommodation and emptying, psychological stressors (PS), Helicobacter pylori (HP) infection, and post-infectious FD. METHODS: Diagnosis of FD was based on ROME III criteria. Clinical evaluation including dyspeptic symptom scoring and assessment for PS was performed. Satiety drink test for gastric accommodation, gastroscopy with biopsy for HP infection, and solid meal gastric emptying were performed. Sixty-seven healthy children were enrolled for assessing PS and satiety drink test. RESULTS: Fifty-five FD children (33 boys, age 12 [6-18] years) with symptoms for 4 (2-48) months and dyspeptic score of 5 (1-13) were enrolled. PS were more common in FD than in controls (46/55 vs 9/67; P < 0.001). Median satiety drink volume was 360 mL (180-1320 mL); no patients had satiety drink volume of < 5th centile of healthy children. The frequency (98% vs 85%; P = 0.01) and severity (65 [10-175] vs 50 [5-130]; P < 0.001) of postprandial symptoms were higher in FD than in controls. Of the postprandial symptoms, pain (20.3% vs 0%; P = 0.000) was present only in FD. Delayed gastric emptying was present in 6.5%, HP infection in 11%, and post-infectious FD in 13% cases. Etiological factor was identified in 87% children, with 20% having multiple factors. CONCLUSIONS: Abnormality of gastric sensorimotor function is seen in one-fourth of FD cases. HP infection and post-infectious FD are present in 11% and 13% cases, respectively.

PET/CT features of extrapulmonary tuberculosis at first clinical presentation: a cross-sectional observational 18F-FDG imaging study across six countries.

BACKGROUND: A large proportion of the huge global burden of extrapulmonary tuberculosis (EPTB) cases are treated empirically without accurate definition of disease sites and extent of multi-organ disease involvement. Positron emission tomography (PET) imaging using 2-deoxy-2-(fluorine-18) fluoro-d-glucose (18F-FDG) in tuberculosis could be a useful imaging technique for localising disease sites and extent of disease. METHODS: We conducted a study of HIV-negative adult patients with a new clinical diagnosis of EPTB across eight centres located in six countries: India, Pakistan, Thailand, South Africa, Serbia and Bangladesh, to assess the extent of disease and common sites involved at first presentation. 18F-FDG PET/computed tomography (CT) scans were performed within 2 weeks of presentation. FINDINGS: 358 patients with EPTB (189 females; 169 males) were recruited over 45 months, with an age range of 18-83 years (females median 30 years; males median 38 years). 350 (98%) out of 358 patients (183 female, 167 male) had positive scans. 118 (33.7%) out of 350 had a single extrapulmonary site and 232 (66.3%) out of 350 had more than one site (organ) affected. Lymph nodes, skeleton, pleura and brain were common sites. 100 (28%) out of 358 EPTB patients had 18F-FDG PET/CT-positive sites in the lung. 110 patients were 18F-FDG PET/CT-positive in more body sites than were noted clinically at first presentation and 160 patients had the same number of positive body sites. INTERPRETATION: 18F-FDG PET/CT scan has potential for further elucidating the spectrum of disease, pathogenesis of EPTB and monitoring the effects of treatment on active lesions over time, and requires longitudinal cohort studies, twinned with biopsy and molecular studies.

Sequential 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) scan findings in patients with extrapulmonary tuberculosis during the course of treatment-a prospective observational study.

BACKGROUND: Initial studies of tuberculosis (TB) in macaques and humans using 18F-FDG positron emission tomography (PET) imaging as a research tool suggest its usefulness in localising disease sites and as a clinical biomarker. Sequential serial scans in patients with extrapulmonary TB (EPTB) could inform on the value of PET-CT for monitoring response to treatment and defining cure. PATIENTS AND METHODS: HIV-negative adults with EPTB from eight sites across six countries had three 18F-FDG PET/CT scans: (i) within 2 weeks of enrolment, (ii) at 2 months into TB treatment and (iii) at end of ATT treatment. Scanning was performed according to the EANM guidelines. 18F-FDG PET/CT scans were performed 60 ± 10 min after intravenous injection of 2.5-5.0 MBq/kg of 18F-FDG. FINDINGS: One hundred and forty-seven patients with EPTB underwent 3 sequential scans. A progressive reduction over time of both the number of active sites and the uptake level (SUVmax) at these sites was seen. At the end of WHO recommended treatment, 53/147 (36.0%) patients had negative PET/CT scans, and 94/147 (63.9%) patients remained PET/CT positive, of which 12 patients had developed MDR TB. One died of brain tuberculoma. INTERPRETATION: Current 18F-FDG PET/CT imaging technology cannot be used clinically as a biomarker of treatment response, cure or for decision-making on when to stop EPTB treatment. PET/CT remains a research tool for TB and further development of PET/CT is required using new Mycobacterium tuberculosis-specific radiopharmaceuticals targeting high-density surface epitopes, gene targets or metabolic pathways.

Low-cost Fluorescein as an Alternative to Radio-colloid for Sentinel Lymph Node Biopsy-a Prospective Validation Study in Early Breast Cancer.

BACKGROUND: Sentinel lymph node biopsy (SLNB) using radio-pharmaceutical (RP) and a blue dye is gold standard for axillary staging in clinically node-negative early breast cancer. High costs and limited availability of RP and/or gamma probe are major deterrents in performing SLNB in developing countries. Fluorescence-guided SLNB can obviate the need for RP and gamma probe. Fluorescein is an inexpensive fluorescent lymphatic tracer. In this study, we compared SLN identification rate (SLN-IR) and false negative rates (FNR) of fluorescein-guided SLNB and radio-guided SLNB using 99mTc-Sulfur-colloid, in isolation, or in combination with methylene blue dye (MBD). METHODS: Sixty-five cN0 early and large operable breast cancer patients underwent validation SLNB using fluorescein (and blue LED light), 99mTc-Sulfur-colloid (and gamma probe) and MBD. Inj Fluorescein 4% was injected, 1 ml each peri-tumoral and sub-areolar five minutes before axillary incision. Axillary dissection was performed irrespective of SLNB histology. The SLN-IR and FNR with various tracers and their combinations were compared. RESULTS: The mean number of SLNs identified was 3.5 ± 1.8 (range 1-6). The SLN-IR using RP alone was 94%, fluorescein alone was 92%, and MBD alone was 82%. The SLN-IR using fluorescein plus MBD combination was 95.4%, compared to 97% using MBD plus RP combination. FNR was 6.3% using fluorescein plus MBD, as well as RP plus MBD combinations. CONCLUSIONS: SLN-IR of > 90% and SLN-FNR of < 10% using fluorescein plus MBD combination are in acceptable range, and are comparable to that of RP plus MBD combination. Fluorescein can replace RP for performing SLNB, in combination with MBD.

Design and development of novel p-aminobenzoic acid derivatives as potential cholinesterase inhibitors for the treatment of Alzheimer's disease.

Based on the quantitative structure-activity relationship (QSAR), some novel p-aminobenzoic acid derivatives as promising cholinesterase enzyme inhibitors were designed, synthesized, characterized and evaluated to enhance learning and memory. The in vitro enzyme kinetic study of the synthesized compounds revealed the type of inhibition on the respective acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. The in vivo studies of the synthesized compounds exhibited significant reversal of cognitive deficits in the animal models of amnesia as compared to standard drug donepezil. Further, the ex vivo studies in the specific brain regions like the hippocampus, hypothalamus, and prefrontal cortex regions also exhibited AChE inhibition comparable to standard donepezil. The in silico molecular docking and dynamics simulations studies of the most potent compound 22 revealed the consensual interactions at the active site pocket of the AChE.

Prospective Randomized Trial of Use of In-House Prepared Low-Cost Radiopharmaceutical Versus Commercial Radiopharmaceutical for Sentinel Lymph Node Biopsy in Patients with Early Stage Invasive Breast Cancer.

BACKGROUND: The current standard-of-care for surgical staging of the axilla in clinically node-negative (N0) early breast cancers is sentinel lymph node biopsy (SLNB), which requires expensive radiopharmaceuticals for efficacious results. In-house produced low-cost radiopharmaceuticals may be the solution and have shown efficacy in earlier observational/pilot studies. We compared SLNB using in-house prepared radiopharmaceutical (99mTc-Antimony-colloid) versus commercially marketed radiopharmaceutical (99mTc-Sulphur-colloid) in this prospective randomized study. STUDY DESIGN: 78 clinically N0 early breast cancer patients (T1/2, N0 stages), undergoing primary surgery were prospectively randomized 1:1 into two groups; to receive SLNB using methylene blue, and either 99mTc-Antimony colloid (Group-1) or  99mTc-Sulphur colloid (Group-2). Completion axillary dissection was done in all (validation SLNB). SLNB indices were compared between the groups. RESULTS: The groups were comparable with regard to age, stage, tumour size, hormone receptors and HER2neu status. Cost of the in-house prepared 99mTc-antimony colloid was 16-times lesser compared to 99mTc-sulphur colloid. SLN identification rates (IR) in Groups 1 and 2 were 100 and 97.4% respectively, (p > 0.05). False negative rates (FNR) in Group 1 and 2 were 6.3% (1/16 patients) and 7.7% (1/13 patients), respectively, (p > 0.05). There were no major allergic reactions in either group. CONCLUSION: In this prospective randomized trial on early breast cancer patients, accuracy of SLNB was comparable using in-house prepared, 99mTc-antimony colloid and commercially marketed 99mTc-sulphur colloid as radiopharmaceutical, while 99mTc-antimony colloid was much cheaper than 99mTc-sulphur colloid.

Assessment of gastric emptying in children: Establishment of control values utilizing a standardized vegetarian meal.

BACKGROUND AND AIM: Disorders of gastric emptying constitute an important group of conditions in children. The diagnostic gold standard is scintigraphy, and recommendations for standardization have been published with adult normative data. Pediatric literature lacks standardized age specific normative values. Our aim was to establish normal values of solid phase gastric emptying utilizing scintigraphy in children (5-18 years) using the recommended imaging protocol and standardized meal. METHODS: Gastric emptying was assessed by scintigraphy of a (99m) Tc-labeled vegetarian meal. Image acquisition was dynamic for first hour and static at 2, 3, and 4 h. Results were reported as percent intragastric retention; lag phase defined as time to 5% emptying. RESULTS: Thirty (17 boys) healthy children, mean ages of 9.5 ± 3.1 (range 5 to 16) years, were enrolled. Median values (5th and 95th percentiles) for percent gastric retention at 30 min, 1, 2, 3 and 4 h were 90% (76 and 100%), 77% (56 and 96%), 33% (10 and 71%), 16% (3 and 44%), and 7% (0.5 and 22%). The median (5th and 95th percentiles) lag phase was 18 min (6 and 60 min). Lag phase had no correlation with gastric retention at 4 h. CONCLUSIONS: This study provides valuable normative ranges for solid phase gastric emptying in children. Using adult normative data in children may be inappropriate.

A Comparative Validation of Primary Surgical Versus Post-neo-adjuvant Chemotherapy Sentinel Lymph Node Biopsy for Stage III Breast Cancers.

INTRODUCTION: Sentinel lymph node biopsy (SLNB) is the standard of care for staging N0 primary early breast cancers (EBC). Patients in developing countries mostly present with large (LOBC) or locally advanced cancers (LABC) and are treated with neo-adjuvant chemotherapy (NACT). Accuracy of SLNB in staging stage III N0 and post-NACT N0 patients is uncertain. This prospective validation study on LOBC/LABC patients compared the accuracy of SLNB between primary versus post-NACT surgery. MATERIALS AND METHODS: Fifty T3/T4, N0 patients undergoing primary surgery (Group I) and 70 LOBC/LABC (index stage) treated with NACT and N0 at the time of surgery (Group II) were inducted. Validation SLNB was performed using low-cost methylene-blue and (99m)Tc-Antimony colloid. SLN identification (IR) and false-negative (FNR) rates were compared between the groups. Sub-group analysis was done in Group II per index tumor and nodal stage to identify factors predicting SLN IR and FNR in post-NACT patients. SLN IR and FNR in both groups were compared with those in previously published SLN validation study and meta-analysis in EBC. RESULTS: Using combination of blue-dye and radio-colloid, post-NACT SLN IR and FNR (82.9, 13.5 %) were far inferior to T3/T4 primary surgery group (94, 7.7 %; p values 0.034, 0.041) and in EBC. SLN IR using blue-dye alone was dismally low in post-NACT LABCs. Factors predicting unidentified post-NACT SLN and false-negative SLNB included young age, LVI, skin infiltration, extra-nodal spread or N2a stage, and UOQ tumors. CONCLUSIONS: Accuracy of SLNB in T3, N0 tumors undergoing primary surgery is comparable to that of SLNB for N0 EBC. In post-NACT patients, SLNB IR are lower and FNR are higher. Factors predictive of non-identification and false-negative SLNB include pre-NACT skin involvement (T4b), N2a stage or extra-nodal invasion and LVI, and to a lesser extent, young age and UOQ location of the tumor.

Very high coronary artery calcium score with normal myocardial perfusion SPECT imaging is associated with a moderate incidence of severe coronary artery disease.

PURPOSE: Myocardial perfusion imaging (MPI) has limitations in the presence of balanced multivessel disease (MVD) and left main (LM) coronary artery disease, occasionally resulting in false-normal results despite the high cardiovascular risk associated with this condition. The purpose of this study was to assess the incidence of severe coronary artery disease (CAD) in the presence of a very high Agatston coronary artery calcium (CAC) score (>1,000) in stable symptomatic patients without known CAD but with normal MPI results. METHODS: A total of 2,659 prospectively acquired consecutive patients were referred for MPI and evaluation of CAC score by CT. Of this patient population, 8 % (222/2,659) had ischemia without myocardial infarction (MI) on MPIand 11 % (298/2,659) had abnormal MPI (MI and/or ischemia). On presentation 1 % of the patients (26/2,659) were symptomatic, had a CAC score >1,000 and normal MPI results. The definition of normal MPI was strict and included a normal hemodynamic response without ischemic ECG changes and normal imaging, particularly absence of transient ischemic dilation. All of these 26 patients with a CAC score >1,000 and normal MPI findings underwent cardiac catheterization. RESULTS: Of these 26 patients, 58 % (15/26) had severe disease (≥70 % stenosis) leading to revascularization. Of this group, 47 % (7/15) underwent percutaneous intervention, and 53 % (8/15) underwent coronary artery bypass grafting. All of these 15 patients had either MVD (14/15) or LM coronary artery disease (1/15), and represented 0.6 % (15/2,659) of all referred patients (95 % CI 0.3 - 0.9 %). The majority, 90 % (8/9), had severe CAD with typical chest pain. CONCLUSION: A very high CAC score (>1,000) with normal MPI in a small subset of symptomatically stable patients was associated with a moderate incidence of severe CAD (95 % CI 37 - 77 %). Larger studies and/or a meta-analysis of small studies are needed to more precisely estimate the incidence of CAD in this population. This study also supports the concept that a normal MPI result in patients with severe CAD may be due to balanced MVD.

Preoperative contrast-enhanced computerized tomography should not delay radioiodine ablation in differentiated thyroid carcinoma patients.

BACKGROUND: There is concern about potential interference of iodinated contrast used in contrast-enhanced computerized tomography (CECT) with radioiodine therapy in differentiated thyroid carcinoma (DTC). The aim of this study was to determine the effect of iodinated contrast on urinary iodine concentration (UIC) in patients having thyroidectomy compared with control groups without CECT and without thyroidectomy. METHODS: This prospective control study consisted of 4 groups each comprising 32 patients. Group 1- DTC patients undergoing preoperative CECT, group 2- DTC patients not undergoing CECT, group 3- benign goiter patients undergoing preoperative CECT, and group 4- patients with non-thyroidal diseases undergoing preoperative CECT. Spot UIC before CECT, after surgery (5-7 d), and at follow-up (4-6 wk) were compared among the groups. RESULTS: The median basal UIC levels were not significantly different between the four groups (232.2 versus 263.9 versus 268.2 versus 178.2 µg/L, respectively, P = 0.443). In contrast, groups having preoperative CECT had significantly higher UIC levels at discharge (924 versus 329 versus 776 versus 661 µg/L, respectively, P = 0.001). These differences became insignificant at follow-up (225 versus 252 versus 310 versus 275 µg/L, respectively, P = 0.505). Patients having follow-up UIC values above the conventional cut-off of clinically relevant iodine excess (>200 µg/L) also had significantly higher basal values than those having lower follow-up values (283.0 versus 181.7 µg/L; P = 0.037). CONCLUSIONS: Irrespective of the fact whether a patient is thyroidectomized or not preoperative CECT using non-lipophilic contrast does not result in long-term iodine retention.

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.

Automated Synthesis of [11C]PiB via [11CH3OTf]-as Methylating Agent for PET Imaging of ß-Amyloid.

AIM: Efficient synthesis of precursor from commercially available starting materials and automated radiosynthesis of [11C]PiB using commercially available dedicated [11C]- Chemistry module from the synthesized precursor. BACKGROUND: [11C]PiB is a promising radiotracer for PET imaging of ß-Amyloid, advancing Alzheimer's disease research. The availability of precursors and protocols for efficient radiolabelling foster the applications of any radiotracer. Efficient synthesis of PiB precursor was performed using anisidine and 4-nitrobenzoyl chloride as starting materials in 5 steps, having addition, substitutions, and cyclization chemical methodologies. This precursor was used for fully automated radiosynthesis of [11C]PiB in a commercially available synthesizer, MPS-100 (SHI, Japan). The synthesized [11C]PiB was purified via solid-phase methodology, and its quality control was by the quality and safety criteria required for clinical use. METHODS: The synthesis of desired precursors and standard authentic compounds started with commercially available materials with 70-80% yields. The standard analytical methods characterized all synthesized compounds. The fully automated [11C]-chemistry synthesizer (MPS-100) used for radiosynthesis of [11C]PiB with [11C]CH3OTf acts as a methylating agent. For radiolabelling, varied amounts of precursor and time of reaction were explored. The resulting crude product underwent purification through solid-phase cartridges. The synthesized radiotracer was analyzed using analytical tools such as radio TLC, HPLC, pH endo-toxicity, and half-life. RESULTS: The precursor for radiosynthesis of [11C]PiB was achieved in excellent yield using simple and feasible chemistry. A protocol for radiolabelling of precursor to synthesized [11C]PiB was developed using an automated synthesizer. The crude radiotracer was purified by solid-phase cartridge, with a decay-corrected radiochemical yield of 40±5% and radiochemical purity of more than 97% in approx 20 minutes (EOB). The specific activity was calculated and found in a 110-121 mCi/µmol range. CONCLUSION: A reliable methodology was developed for preparing precursor followed by fully automated radiolabeling using [11C]MeOTf as a methylating agent to synthesize [11C]PiB. The final HPLC-free purification yielded more than 97% radiochemical purity tracer within one radionuclide half-life. The method was reproducible and efficient for any clinical center.

Renal artery involvement is associated with increased morbidity but not mortality in Takayasu arteritis: a matched cohort study of 215 patients.

BACKGROUND: We analyzed differences in presentation and survival of Takayasu arteritis (TAK) with or without renal artery involvement (RAI) from a large monocentric cohort of patients with TAK. METHODS: Clinical and angiographic features were compared between TAK with versus without RAI, with bilateral versus unilateral RAI, and with bilateral RAI versus without RAI using multivariable-adjusted logistic regression. Inter-group differences in survival were analyzed [hazard ratios (HR) with 95% confidence intervals (95%CI)] adjusted for gender, age at disease onset, diagnostic delay, baseline disease activity, and significant clinical/angiographic inter-group differences after multivariable-adjustment/propensity score matching (PSM). RESULTS: Of 215 TAK, 117(54.42%) had RAI [66(56.41%) bilateral]. TAK with RAI or with bilateral RAI had earlier disease onset than without RAI (p < 0.001). Chronic renal failure (CRF) was exclusively seen in TAK with RAI. TAK with RAI (vs without RAI) had more frequent hypertension (p = 0.001), heart failure (p = 0.047), abdominal aorta (p = 0.001) or superior mesenteric artery involvement (p = 0.018). TAK with bilateral RAI (vs unilateral RAI) more often had hypertension (p = 0.011) and blurring of vision (p = 0.049). TAK with bilateral RAI (vs without RAI) more frequently had hypertension (p = 0.002), heart failure (p = 0.036), abdominal aorta (p < 0.001), superior mesenteric artery (p = 0.002), or left subclavian artery involvement (p = 0.041). Despite higher morbidity (hypertension, CRF), mortality risk was not increased with RAI vs without RAI (HR 2.32, 95%CI 0.61-8.78), with bilateral RAI vs unilateral RAI (HR 2.65, 95%CI 0.52-13.42) or without RAI (HR 3.16, 95%CI 0.79-12.70) even after multivariable adjustment or PSM. CONCLUSION: RAI is associated with increased morbidity (CRF, hypertension, heart failure) but does not adversely affect survival in TAK. Key Points •Renal artery involvement in TAK is associated with chronic renal failure. •TAK with renal artery involvement more often have heart failure and hypertension. •Bilateral renal artery involvement (compared with unilateral) is more often associated with hypertension and visual symptoms. •Renal artery involvement is not associated with an increased risk of mortality in TAK.

Insight into Tumor Hypoxia: Radionuclide-based Biomarker as Diagnostic Tools.

The radiolabeled tracers have been extensively utilized to access various physiological and pathological conditions non-invasively, such as cancers, inflammation, and organ-specific imaging. These tracers demonstrate and study tumor hypoxia in several malignancies. Hypoxia is commonly seen in solid tumors. Tumor Hypoxia is a non-physiological condition of reduced oxygen concentration in the tumor. Hypoxia is associated with adverse outcomes such as treatment resistance and metastases in solid tumors. Tumor hypoxia may result in resistance to radiation therapy and chemotherapy, leading to a poor prognosis. It is one of the clinically paramount factors in treatment planning. Various chemical scaffolds are labeled with compatible radioisotopes for imaging hypoxia by Single-photon emission computed tomography (SPECT) and Positron emission tomography (PET). Radionuclides, such as [18F]Flourine, [99mTc]Technetium, [131I]Iodine, [124I] Iodine, and [64Cu]Copper are used for incorporation into different chemical scaffolds.Among them, [18F]Flourine and [64Cu]Copper tagged radiopharmaceuticals are most explored, such as [18F]FMISO, [18F]FAZA, [18F]FETNIM, and N4-methyl thiosemicarbazone [64Cu][Cu (ATSM)]. Some of the promising scaffolds for imaging hypoxia are [18F]EF1, [18F]EF5, [18F]EF3, and [18F]HX4. This review is focused on developing radiochemistry routes to synthesize different radiopharmaceuticals for imaging hypoxia in clinical and preclinical studies, as described in the literature. The chemist and radiochemist exerted enormous efforts to overcome these obstacles. They have successfully formulated multiple radiopharmaceuticals for hypoxia imaging. Radionuclide incorporation in high selectivity and efficiency (radiochemical yield, specific activity, purity, and radio-scalability) is a need for application perspective. Versatile chemistry, including nucleophilic and electrophilic substitutions, allows the direct or indirect introduction of radioisotopes into molecules of interest. This review will discuss the chemical routes for synthesizing and utilizing different precursors for radiolabeling with radionuclides.We will briefly summaries these radio-labeled tracers' application and biological significance.

Extensive Extramedullary Involvement at Presentation in B-Cell Acute Lymphoblastic Leukemia.

ABSTRACT: Extensive extramedullary involvement as presentation is uncommon in pediatric B-cell acute lymphoblastic leukemia. A 7-year-old boy was diagnosed with painless parotid gland enlargement. He had pancytopenia and significantly raised serum lactate dehydrogenase. Fine-needle aspiration cytology from the parotid was suggestive of lymphoid malignancy. Flow cytometry and bone marrow biopsy suggested B-cell acute lymphoblastic leukemia. 18 F-FDG PET/CT revealed extensive bone marrow disease and the involvement of the spleen, pancreas, kidneys, and the parotid, submandibular, and lacrimal glands. He had negligible physiological brain uptake.

18 F-FDG PET/CT in Extensive Follicular Dendritic Cell Sarcoma With Response Assessment to Chemotherapy.

ABSTRACT: Follicular dendritic cell sarcoma (FDCS) is a low-grade sarcoma of mesenchymal dendritic cell origin, and it constitutes <0.4% of soft tissue sarcomas. We report a rare case of FDCS in a 32-year-old man. 18 F-FDG PET/CT demonstrated the involvement of cervical, axillary, mediastinal, abdominal, and pelvic groups of lymph nodes and spleen. A cervical lymph node biopsy suggested FDCS. 18 F-FDG PET/CT scan done after 3 cycles of chemotherapy (CHOP regime) revealed a complete metabolic response. This case presents the rarity of extensive presentation and complete response to the CHOP regime.