Efficacy and safety of creatine supplementation in childhood-onset systemic lupus erythematosus: a randomized, double-blind, placebo-controlled, crossover trial.

INTRODUCTION: Creatine supplementation has emerged as a promising non-pharmacological therapeutic strategy to counteract muscle dysfunction and low lean mass in a variety of conditions, including in pediatric and rheumatic diseases. The objective of this study was to examine the efficacy and safety of creatine supplementation in childhood systemic lupus erythematosus (C-SLE). METHODS: C-SLE patients with mild disease activity (n = 15) received placebo or creatine supplementation in a randomized fashion using a crossover, double-blind, repeated-measures design. The participants were assessed at baseline and after 12 weeks in each arm, interspersed by an eight-week washout period. The primary outcomes were muscle function, as assessed by a battery of tests including one-maximum repetition (1-RM) tests, the timed-up-and-go test, the timed-stands test, and the handgrip test. Secondary outcomes included body composition, biochemical markers of bone remodeling, aerobic conditioning, quality of life, and physical capacity. Possible differences in dietary intake were assessed by three 24-hour dietary recalls. Muscle phosphorylcreatine content was measured through phosphorus magnetic resonance spectroscopy (31 P-MRS). The safety of the intervention was assessed by laboratory parameters, and kidney function was measured by (51)Cr-EDTA clearance. Additionally, self-reported adverse events were recorded throughout the trial. RESULTS: Intramuscular phosphorylcreatine content was not significantly different between creatine and placebo before or after the intervention (creatine-Pre: 20.5 ± 2.6, Post: 20.4 ± 4.1, placebo-Pre: 19.8 ± 2.0; Post: 20.2 ± 3.2 mmol/kg wet muscle; p = 0.70 for interaction between conditions). In addition, probably as a consequence of the lack of change in intramuscular phosphorylcreatine content, there were no significant changes between placebo and creatine for any muscle function and aerobic conditioning parameters, lean mass, fat mass, bone mass, and quality of life scores (p > 0.05). The (51)Cr-EDTA clearance was not altered by creatine supplementation and no side effects were noticed. CONCLUSION: A 12-week creatine supplementation protocol at 0.1 g/kg/d is well tolerated and free of adverse effects but did not affect intramuscular phosphorylcreatine, muscle function, free-fat mass or quality of life in non-active C-SLE patients. TRIAL REGISTRATION: Clinicaltrials.gov number: NCT01217320.

Cyst infection in hospital-admitted autosomal dominant polycystic kidney disease patients is predominantly multifocal and associated with kidney and liver volume

Positron-emission tomography/computed tomography (PET/CT) has improved cyst infection (CI) management in autosomal dominant polycystic kidney disease (ADPKD). The determinants of kidney and/or liver involvement, however, remain uncertain. In this study, we evaluated clinical and imaging factors associated with CI in kidney (KCI) and liver (LCI) in ADPKD. A retrospective cohort study was performed in hospital-admitted ADPKD patients with suspected CI. Clinical, imaging and surgical data were analyzed. Features of infected cysts were evaluated by PET/CT. Total kidney (TKV) and liver (TLV) volumes were measured by CT-derived multiplanar reconstruction. CI was detected in 18 patients who experienced 24 episodes during an interval of 30 months (LCI in 12, KCI in 10 and concomitant infection in 2). Sensitivities of CT, magnetic resonance imaging and PET/CT were 25.0, 71.4, and 95.0%. Dysuria (P<0.05), positive urine culture (P<0.01), and previous hematuria (P<0.05) were associated with KCI. Weight loss (P<0.01) and increased C-reactive protein levels (P<0.05) were associated with LCI. PET/CT revealed that three or more infected cysts were present in 70% of the episodes. TKV was higher in kidney-affected than in LCI patients (AUC=0.91, P<0.05), with a cut-off of 2502 mL (72.7% sensitivity, 100.0% specificity). TLV was higher in liver-affected than in KCI patients (AUC=0.89, P<0.01) with a cut-off of 2815 mL (80.0% sensitivity, 87.5% specificity). A greater need for invasive procedures was observed in LCI (P<0.01), and the overall mortality was 20.8%. This study supports PET/CT as the most sensitive imaging method for diagnosis of cyst infection, confirms the multifocal nature of most hospital-admitted episodes, and reveals an association of kidney and liver volumes with this complication.

Cyst infection in hospital-admitted autosomal dominant polycystic kidney disease patients is predominantly multifocal and associated with kidney and liver volume.

Positron-emission tomography/computed tomography (PET/CT) has improved cyst infection (CI) management in autosomal dominant polycystic kidney disease (ADPKD). The determinants of kidney and/or liver involvement, however, remain uncertain. In this study, we evaluated clinical and imaging factors associated with CI in kidney (KCI) and liver (LCI) in ADPKD. A retrospective cohort study was performed in hospital-admitted ADPKD patients with suspected CI. Clinical, imaging and surgical data were analyzed. Features of infected cysts were evaluated by PET/CT. Total kidney (TKV) and liver (TLV) volumes were measured by CT-derived multiplanar reconstruction. CI was detected in 18 patients who experienced 24 episodes during an interval of 30 months (LCI in 12, KCI in 10 and concomitant infection in 2). Sensitivities of CT, magnetic resonance imaging and PET/CT were 25.0, 71.4, and 95.0%. Dysuria (P<0.05), positive urine culture (P<0.01), and previous hematuria (P<0.05) were associated with KCI. Weight loss (P<0.01) and increased C-reactive protein levels (P<0.05) were associated with LCI. PET/CT revealed that three or more infected cysts were present in 70% of the episodes. TKV was higher in kidney-affected than in LCI patients (AUC=0.91, P<0.05), with a cut-off of 2502 mL (72.7% sensitivity, 100.0% specificity). TLV was higher in liver-affected than in KCI patients (AUC=0.89, P<0.01) with a cut-off of 2815 mL (80.0% sensitivity, 87.5% specificity). A greater need for invasive procedures was observed in LCI (P<0.01), and the overall mortality was 20.8%. This study supports PET/CT as the most sensitive imaging method for diagnosis of cyst infection, confirms the multifocal nature of most hospital-admitted episodes, and reveals an association of kidney and liver volumes with this complication.

Graves' disease radioiodine-therapy: choosing target absorbed doses for therapy planning.

PURPOSE: The precise determination of organ mass (mth) and total number of disintegrations within the thyroid gland (Ã) are essential for thyroid absorbed-dose calculations for radioiodine therapy. Nevertheless, these parameters may vary according to the method employed for their estimation, thus introducing uncertainty in the estimated thyroid absorbed dose and in any dose-response relationship derived using such estimates. In consideration of these points, thyroid absorbed doses for Graves' disease (GD) treatment planning were calculated using different approaches to estimating the mth and the Ã. METHODS: Fifty patients were included in the study. Thyroid (131)I uptake measurements were performed at 2, 6, 24, 48, 96, and 220 h postadministration of a tracer activity in order to estimate the effective half-time (Teff) of (131)I in the thyroid; the thyroid cumulated activity was then estimated using the Teff thus determined or, alternatively, calculated by numeric integration of the measured time-activity data. Thyroid mass was estimated by ultrasonography (USG) and scintigraphy (SCTG). Absorbed doses were calculated with the OLINDA∕EXM software. The relationships between thyroid absorbed dose and therapy response were evaluated at 3 months and 1 year after therapy. RESULTS: The average ratio (± 1 standard deviation) between mth estimated by SCTG and USG was 1.74 (± 0.64) and that between à obtained by Teff and the integration of measured activity in the gland was 1.71 (± 0.14). These differences affect the calculated absorbed dose. Overall, therapeutic success, corresponding to induction of durable hypothyroidism or euthyroidism, was achieved in 72% of all patients at 3 months and in 90% at 1 year. A therapeutic success rate of at least 95% was found in the group of patients receiving doses of 200 Gy (p = 0.0483) and 330 Gy (p = 0.0131) when mth was measured by either USG or SCTG and à was determined by the integration of measured (131)I activity in the thyroid gland and based on Teff, respectively. No statistically significant relationship was found between therapeutic response and patients' age, administered (131)I activity (MBq), 24-h thyroid (131)I uptake (%) or Teff (p ≥ 0.064); nonetheless, a good relationship was found between the therapeutic response and mth (p ≤ 0.035). CONCLUSIONS: According to the results of this study, the most effective thyroid absorbed dose to be targeted in GD therapy should not be based on a fixed dose but rather should be individualized based on the patient's mth and Ã. To achieve a therapeutic success (i.e., durable euthyroidism or hypothyroidism) rate of at least 95%, a thyroid absorbed dose of 200 or 330 Gy is required depending on the methodology used for estimating mth and Ã.

Primary chemotherapy effect in sentinel node detection in breast cancer.

PURPOSE: Sentinel node (SN) biopsy is a reliable method for improved staging of breast cancer, offering an alternative to routine axillary dissection. Perhaps preoperative chemotherapy could increase the rate of false-negative SN because of induced lymphatic changes. The aim of the study was to evaluate the utility of lymphoscintigraphy and of hand-held probe detection in the SN approach after chemotherapy, correlating it with histologic analysis of the axilla. METHODS: Eighty-three patients (mean age, 53 years; TNM stage I) were studied prospectively. They were separated into two groups: group 1 (G1), 37 patients with preoperative chemotherapy and group 2 (G2), 46 patients without chemotherapy. Mean tumor size was 2 cm in both groups. Lymphoscintigraphy was performed 3 to 4 hours after peritumoral injection of Tc-99m dextran-70 in a 0.2-ml volume and activity of 14.8 MBq (0.4 mCi), performed under ultrasound or mammographic control. On the following day, each patient underwent tumor resection with axillary dissection, included the SN. RESULTS: The SN was detected by scintigraphy in 78 patients (94%). The failure of SN to predict the axillary histologic status was significantly higher (P = 0.01) in G1 than in G2 (7 and 1 false-negative result, respectively). CONCLUSION: Preoperative chemotherapy seems to impair axillary evaluation by SN biopsy and should be used cautiously in this subset of patients.

The use of 99mTc-phytate for sentinel node mapping in melanoma, breast cancer and vulvar cancer: a study of 100 cases.

Sentinel node mapping reduces surgical morbidity and allows the use of more accurate tumour staging techniques. Radionuclide studies are preferentially performed using small colloids, which have limited availability in our country. The possibility of using phytate for sentinel node mapping was raised because of the similarity between its biodistribution and that of nanocolloids in the reticulo-endothelial system. In this paper we evaluated the use of 99mTc-phytate for sentinel node mapping, correlating the histopathological results with the status of the rest of the lymph node chain in different malignant tumours. A total of 100 patients were studied. group 1 consisted of 62 patients with breast cancer, group 2 of 20 patients with melanoma and group 3 of 18 patients with vulvar carcinoma. Lymph node scintigraphy was carried out after injecting 99mTc-phytate subdermally, and the sentinel node projection was marked on the skin. After 18-24 h, intraoperative sentinel node localisation was performed using a gamma probe (combined with visual localisation using patent blue dye) in 75 patients, and lymph node dissection was then carried out. Radionuclide scintigraphy identified the sentinel node in 98% of all studies. Intraoperative detection using the gamma probe was equally efficient: group 1=93% (38/41), group 2=95% (18/19) and group 3=100% (15/15). The sentinel node was involved in 41%, 31% and 20% of cases in groups 1, 2 and 3, respectively. Among the patients with positive nodes, the sentinel node was the only one affected in 53% of group 1, 50% of group 2 and 67% of group 3 cases. The method's negative predictive value was 91% in group 1 and 100% in the other groups. One false-negative study occurred in a patient who had a multifocal tumour and an intraparenchymatous lymph node; another occurred in a patient with a macroscopically affected node found during surgery. There were no side-effects related to the 99mTc-phytate. It is concluded that scintigraphic and intraoperative sentinel node identification was satisfactorily performed using 99mTc-phytate. The results were comparable to those previously described in the literature using other radiopharmaceuticals. Easy availability and low cost justify the use of phytate in our practice.

The use of (99m)Tc-phytate for sentinel node mapping in melanoma, breast cancer and vulvar cancer: a study of 100 cases.

Sentinel node mapping reduces surgical morbidity and allows the use of more accurate tumour staging techniques. Radionuclide studies are preferentially performed using small colloids, which have limited availability in our country. The possibility of using phytate for sentinel node mapping was raised because of the similarity between its biodistribution and that of nanocolloids in the reticulo-endothelial system. In this paper we evaluated the use of (99m)Tc-phytate for sentinel node mapping, correlating the histopathological results with the status of the rest of the lymph node chain in different malignant tumours. A total of 100 patients were studied. group 1 consisted of 62 patients with breast cancer, group 2 of 20 patients with melanoma and group 3 of 18 patients with vulvar carcinoma. Lymph node scintigraphy was carried out after injecting (99m)Tc-phytate subdermally, and the sentinel node projection was marked on the skin. After 18-24 h, intraoperative sentinel node localisation was performed using a gamma probe (combined with visual localisation using patent blue dye) in 75 patients, and lymph node dissection was then carried out. Radionuclide scintigraphy identified the sentinel node in 98% of all studies. Intraoperative detection using the gamma probe was equally efficient: group 1=93% (38/41), group 2=95% (18/19) and group 3=100% (15/15). The sentinel node was involved in 41%, 31% and 20% of cases in groups 1, 2 and 3, respectively. Among the patients with positive nodes, the sentinel node was the only one affected in 53% of group 1, 50% of group 2 and 67% of group 3 cases. The method's negative predictive value was 91% in group 1 and 100% in the other groups. One false-negative study occurred in a patient who had a multifocal tumour and an intraparenchymatous lymph node; another occurred in a patient with a macroscopically affected node found during surgery. There were no side-effects related to the (99m)Tc-phytate. It is concluded that scintigraphic and intraoperative sentinel node identification was satisfactorily performed using (99m)Tc-phytate. The results were comparable to those previously described in the literature using other radiopharmaceuticals. Easy availability and low cost justify the use of phytate in our practice.

[Evaluation of inflammatory activity in chronic osteomyelitis. Contribution of scintigraphy with polyclonal antibodies]. / Avaliação de atividade inflamatória na osteomielite crônica. Contribuição da cintilografia com anticorpos policlonais.

BACKGROUND: Active chronic osteomyelitis or complicating osteomyelitis are difficult to be diagnosed by radiological imaging modalities, such as plain radiograph and CT. They frequently cause increased bone remodeling, leading to nonspecific uptake of Tc-99m-bone scan agents and gallium-67. New radiopharmaceuticals with greater infection avidity are being developed, including the nonspecific polyclonal immunoglobulin (IgG) labeled with technetium-99m. Tc-99m-IgG may be available as a ready to use kit, with no reported side effects, low patient absorbed radiation dose and low cost. MATERIAL AND METHODS: 23 bone segments with suspected active chronic osteomyelitis or violated bone osteomyelitis were studied by Tc-99m-IgG scintigraphy. All patients underwent standard three-phase bone scintigraphy using methylene diphosphonate (Tc-99m-MDP), gallium-67 scintigraphy and plain radiographs, compared with clinical evaluation and laboratory tests values. RESULTS: Infection was found in 8 sites. Sensitivity and specificity for Tc-99m-MDP, gallium-67 and Tc-99m-IgG scintigraphy were, respectively, 88 and 36%, 75 and 73%, 88 and 82%. CONCLUSION: Tc-99m-IgG may be usefull in the scintigraphic evaluation of osteomyelitis.

Avaliaçäo de atividade inflamatória na osteomielite crônica: contribuiçäo da cintilografia com anticorpos policlonais / Evaluation of inflammatory activity in chronic osteomyelitis: contribution of scintigraphy with polyclonal antibodies

OBJETIVO: O diagnóstico de osteomielite crônica em atividade ou sobreposta a outras patologias é difícil, pois estas situações mascaram os achados radiológicos de infecção. A especificidade da cintilografia do esqueleto ou com gálio-67 também é reduzida pela influência da remodelação óssea na captação destes radiofármacos. Anticorpos policlonais marcados com tecnécio-99m (Tc-99m-IgG) apresentam captação independente do metabolismo ósseo, sendo um dos radiofármacos em investigação para avaliação mais específica de infecção. CASUÍSTICA E MÉTODO: Neste estudo comparou-se a cintilografia com Tc-99m-IgG, cintilografia óssea trifásica e cintilografia com gálio-67 no diagnóstico da osteomielite crônica em atividade em 23 segmentos ósseos; correlacionando-as com dados clínico-laboratoriais e radiológicos. RESULTADOS: Oito dos 23 segmentos foram classificados como infectados, 11 não infectados e quatro inconclusivos. A sensibilidade e especificidade encontradas para cintilografia óssea, com gálio-67 e com Tc-99m-IgG foram, respectivamente, 88 e 36 por cento, 75 e 73 por cento, 88 e 82 por cento. CONCLUSÃO: Os resultados sugerem que a Tc-99m-IgG possa ser utilizada no diagnóstico da osteomielite crônica em atividade.

Gallbladder emptying in normal volunteers. Comparative study between cholescintigraphy and ultrasonography.

To assess the reproducibility of and compare the patterns of gallbladder emptying after a fatty meal stimulus, the authors analyzed 10 healthy fasting volunteers (8 men; mean age, 32 years). Cholescintigraphy was obtained after intravenous injection of 185 MBq of Tc-99m DISIDA. A standardized fatty meal was provided 70 minutes after injection. The ejection fraction was measured sequentially by ultrasound and cholescintigraphy 15, 30, 45, and 60 minutes after eating. All patients had repeat studies within 1-3 weeks. The two methods showed a distinct gallbladder time course of emptying after the fatty meal stimulus. Nuclear medicine showed higher values of gallbladder ejection fraction at 45 and 60 minutes after eating when compared to ultrasound (P < 0.01). The plotted curves, using the four different periods of time, also showed different behavior due mainly to distinct angular coefficients (nuclear medicine, 2.6; ultrasound, 0.9). Good reproducibility of fatty meal-induced gallbladder ejection fraction at 30, 45, and 60 minutes was also observed using both methods. Thus, ultrasound and nuclear medicine are reproducible methods of studying gallbladder dynamics. However, nuclear medicine demonstrated continued excretion of bile at 45 and 60 minutes, whereas ultrasound did not show significant volume variations in these time frames.