The effect of antifibrotic agents on acute respiratory failure in COVID-19 patients: a retrospective cohort study from TriNetX US collaborative networks.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on global health and economies, resulting in millions of infections and deaths. This retrospective cohort study aimed to investigate the effect of antifibrotic agents (nintedanib and pirfenidone) on 1-year mortality in COVID-19 patients with acute respiratory failure. METHODS: Data from 61 healthcare organizations in the TriNetX database were analyzed. Adult patients with COVID-19 and acute respiratory failure were included. Patients with a pre-existing diagnosis of idiopathic pulmonary fibrosis before their COVID-19 diagnosis were excluded. The study population was divided into an antifibrotic group and a control group. Propensity score matching was used to compare outcomes, and hazard ratios (HR) for 1-year mortality were calculated. RESULTS: The antifibrotic group exhibited a significantly lower 1-year mortality rate compared to the control group. The survival probability at the end of the study was 84.42% in the antifibrotic group and 69.87% in the control group. The Log-Rank test yielded a p-value of less than 0.001. The hazard ratio was 0.434 (95% CI: 0.264-0.712), indicating a significant reduction in 1-year mortality in the antifibrotic group. Subgroup analysis demonstrated significantly improved 1-year survival in patients receiving nintedanib treatment and during periods when the Wuhan strain was predominant. DISCUSSION: This study is the first to demonstrate a survival benefit of antifibrotic agents in COVID-19 patients with acute respiratory failure. Further research and clinical trials are needed to confirm the efficacy of these antifibrotic agents in the context of COVID-19 and acute respiratory failure.

Targeting histone deacetylase-3 blocked epithelial-mesenchymal plasticity and metastatic dissemination in gastric cancer.

BACKGROUND AND PURPOSE: Histone deacetylase (HDAC) inhibitors (HDIs) can modulate the epithelial-mesenchymal transition (EMT) progression and inhibit the migration and invasion of cancer cells. Emerging as a novel class of anti-cancer drugs, HDIs are attracted much attention in the field of drug discovery. This study aimed to discern the underlying mechanisms of Honokiol in preventing the metastatic dissemination of gastric cancer cells by inhibiting HDAC3 activity/expression. EXPERIMENTAL APPROACH: Clinical pathological analysis was performed to determine the relationship between HDAC3 and tumor progression. The effects of Honokiol on pharmacological characterization, functional, transcriptional activities, organelle structure changes, and molecular signaling were analyzed using binding assays, differential scanning calorimetry, luciferase reporter assay, HDAC3 activity, ER stress response element activity, transmission electron microscopy, immune-blotting, and Wnt/ß-catenin activity assays. The in vivo effects of Honokiol on peritoneal dissemination were determined by a mouse model and detected by PET/CT tomography. KEY RESULTS: HDAC3 over-expression was correlated with poor prognosis. Honokiol significantly abolished HDAC3 activity (Y298) via inhibition of NFκBp65/CEBPß signaling, which could be reversed by the over-expression of plasmids of NFκBp65/CEBPß. Treatments with 4-phenylbutyric acid (a chemical chaperone) and calpain-2 gene silencing inhibited Honokiol-inhibited NFκBp65/CEBPß activation. Honokiol increased ER stress markers and inhibited EMT-associated epithelial markers, but decreased Wnt/ß-catenin activity. Suppression of HDAC3 by both Honokiol and HDAC3 gene silencing decreased cell migration and invasion in vitro and metastasis in vivo. CONCLUSIONS AND IMPLICATIONS: Honokiol acts by suppressing HDAC3-mediated EMT and metastatic signaling. By prohibiting HDAC3, metastatic dissemination of gastric cancer may be blocked. Conceptual model showing the working hypothesis on the interaction among Honokiol, HDAC3, and ER stress in the peritoneal dissemination of gastric cancer. Honokiol targeting HDAC3 by ER stress cascade and mitigating the peritoneal spread of gastric cancer. Honokiol-induced ER stress-activated calpain activity targeted HDAC3 and blocked Tyr298 phosphorylation, subsequently blocked cooperating with EMT transcription factors and cancer progression. The present study provides evidence to demonstrate that HDAC3 is a positive regulator of EMT and metastatic growth of gastric cancer cells. The findings here imply that overexpressed HDAC3 is a potential therapeutic target for honokiol to reverse EMT and prevent gastric cancer migration, invasion, and metastatic dissemination. • Honokiol significantly abolished HDAC3 activity on catalytic tyrosine 298 residue site. In addition, Honokiol-induced ER stress markedly inhibited HDAC3 expression via inhibition of NFκBp65/CEBPß signaling. • HDAC3, which is a positive regulator of metastatic gastric cancer cell growth, can be significantly inhibited by Honokiol. • Opportunities for HDAC3 inhibition may be a potential therapeutic target for preventing gastric cancer metastatic dissemination.

Evaluation of Chelator-to-Antibody Ratio on Development of 89Zr-iPET Tracer for Imaging of PD-L1 Expression on Tumor.

89Zr-iPET has been widely used for preclinical and clinical immunotherapy studies to predict patient stratification or evaluate therapeutic efficacy. In this study, we prepared and evaluated 89Zr-DFO-anti-PD-L1-mAb tracers with varying chelator-to-antibody ratios (CARs), including 89Zr-DFO-anti-PD-L1-mAb_3X (tracer_3X), 89Zr-DFO-anti-PD-L1-mAb_10X (tracer_10X), and 89Zr-DFO-anti-PD-L1-mAb_20X (tracer_20X). The DFO-anti-PD-L1-mAb conjugates with varying CARs were prepared using a random conjugation method and then subjected to quality control. The conjugates were radiolabeled with 89Zr and evaluated in a PD-L1-expressing CT26 tumor-bearing mouse model. Next, iPET imaging, biodistribution, pharmacokinetics, and ex vivo pathological and immunohistochemical examinations were conducted. LC-MS analysis revealed that DFO-anti-PD-L1-mAb conjugates were prepared with CARs ranging from 0.4 to 2.0. Radiochemical purity for all tracer groups was >99% after purification. The specific activity levels of tracer_3X, tracer_10X, and tracer_20X were 2.2 ± 0.6, 8.2 ± 0.6, and 10.5 ± 1.6 µCi/µg, respectively. 89Zr-iPET imaging showed evident tumor uptake in all tracer groups and reached the maximum uptake value at 24 h postinjection (p.i.). Biodistribution data at 168 h p.i. revealed that the tumor-to-liver, tumor-to-muscle, and tumor-to-blood uptake ratios for tracer_3X, tracer_10X, and tracer_20X were 0.46 ± 0.14, 0.58 ± 0.33, and 1.54 ± 0.51; 4.7 ± 1.3, 7.1 ± 3.9, and 14.7 ± 1.1; and 13.1 ± 5.8, 19.4 ± 13.8, and 41.3 ± 10.6, respectively. Significant differences were observed between tracer_3X and tracer_20X in the aforementioned uptake ratios at 168 h p.i. The mean residence time and elimination half-life for tracer_3X, tracer_10X, and tracer_20X were 25.4 ± 4.9, 24.2 ± 6.1, and 25.8 ± 3.3 h and 11.8 ± 0.5, 11.1 ± 0.7, and 11.7 ± 0.6 h, respectively. No statistical differences were found between-tracer in the aforementioned pharmacokinetic parameters. In conclusion, 89Zr-DFO-anti-PD-L1-mAb tracers with a CAR of 1.4-2.0 may be better at imaging PD-L1 expression in tumors than are traditional low-CAR 89Zr-iPET tracers.

Clinical impacts of scar reduction on gated myocardial perfusion SPECT after cardiac resynchronization therapy.

BACKGROUND: It had not been reported that myocardial scar shown on gated myocardial perfusion SPECT (GMPS) might reduce after cardiac resynchronization therapy (CRT). In this study, we aim to investigate the clinical impact and characteristic of scar reduction (SR) after CRT. METHODS AND RESULTS: Sixty-one heart failure patients following standard indication for CRT received twice GMPS as pre- and post-CRT evaluations. The patients with an absolute reduction of scar ≥ 10% after CRT were classified as the SR group while the rest were classified as the non-SR group. The SR group (N = 22, 36%) showed more improvement on LV function (∆LVEF: 18.1 ± 12.4 vs 9.4 ± 9.9 %, P = 0.007, ∆ESV: - 91.6 ± 52.6 vs - 38.1 ± 46.5 mL, P < 0.001) and dyssynchrony (ΔPSD: - 26.19 ± 18.42 vs - 5.8 ± 23.0°, P < 0.001, Δ BW: - 128.7 ± 82.8 vs - 25.2 ± 109.0°, P < 0.001) than non-SR group (N = 39, 64%). Multivariate logistic regression analysis showed baseline QRSd (95% CI 1.019-1.100, P = 0.006) and pre-CRT Reduced Wall Thickening (RWT) (95% CI 1.016-1.173, P = 0.028) were independent predictors for the development of SR. CONCLUSION: More than one third of patients showed SR after CRT who had more post-CRT improvement on LV function and dyssynchrony than those without SR. Wider QRSd and higher RWT before CRT were related to the development of SR after CRT.

2021 Advocacy Statements for the Role of 99mTc-Pyrophosphate Scintigraphy in the Diagnosis of Transthyretin Cardiac Amyloidosis: A Report of the Taiwan Society of Cardiology and the Society of Nuclear Medicine of the Republic of China.

Transthyretin cardiac amyloidosis (ATTR-CM) is an increasingly recognized cause of heart failure with preserved ejection fraction. Favorable prognosis depends on early diagnosis and correct treatment strategy. Among patients for whom there is a high clinical suspicion of cardiac amyloidosis, 99mTc-labeled bone avid scintigraphy including 99mTc-pyrophosphate (PYP) scintigraphy may be of diagnostic and prognostic importance. Various international guidelines support the non-biopsy diagnosis of ATTR-CM using 99mTc-PYP scintigraphy, yet emphasize the gap in standardization of acquisition and imaging analysis protocols, as well as the appropriateness of its clinical use. Therefore, a joint expert consensus has been reached by the Taiwan Society of Cardiology and the Society of Nuclear Medicine of the Republic of China, to advocate for the application of 99mTc-PYP scintigraphy in the diagnosis of ATTR-CM. This article aims to highlight the recommendations on image acquisition, qualitative and quantitative assessments of cardiac 99mTc-PYP uptake, and diagnostic algorithms. We hope the implementation of these recommendations in Taiwan will facilitate the process and enhance the diagnostic rate of ATTR-CM.

Use of FDG-PET or PET/CT to detect recurrent colorectal cancer in patients with elevated CEA: a systematic review and meta-analysis.

AIM: The purpose of the present study was to conduct a systematic review and meta-analysis of the published literature to assess the diagnostic performance of FDG-PET or PET/CT in the detection of recurrent colorectal cancer (CRC) rising in patients with elevated CEA. MATERIALS AND METHODS: The authors conducted a systematic MEDLINE search of published articles. Two reviewers independently assessed the methodological quality of each study. We estimated pooled sensitivity and specificity and positive and negative likelihood ratios, and summary receiver-operating characteristic curves in the detection of recurrent CRC in patients with elevated CEA. RESULTS: Eleven studies with a total of 510 patients met the inclusion criteria. One hundred and six patients (106/510 = 20.8%) had true-negative FDG-PET (PET/CT) results in detection of recurrent CRC when rising CEA. The pooled estimates of sensitivity and specificity and positive and negative likelihood ratios of FDG-PET in the detection of tumor recurrence in CRC patients with elevated CEA were 90.3% (95% CI, 85.5-94.0%), 80.0% (95% CI, 67.0-89.6%), 2.88 (95% CI, 1.37-6.07), and 0.12 (95% CI, 0.07-0.20), respectively. The pooled estimates of sensitivity and specificity and positive and negative likelihood ratios of FDG-PET/CT in the detection of tumor recurrence in CRC patients with elevated CEA were 94.1% (95% CI, 89.4-97.1%), 77.2% (95% CI, 66.4-85.9%), 4.70 (95% CI, 0.82-12.13), and 0.06 (95% CI, 0.03-0.13), respectively. CONCLUSIONS: Whole-body FDG-PET and PET/CT are valuable imaging tools for the assessment of patients with suspected CRC tumor recurrence based on the increase of CEA.

Morphological and metabolic asymmetries of the thalamic subregions in temporal lobe epilepsy predict cognitive functions.

Both morphological and metabolic imaging were used to determine how asymmetrical changes of thalamic subregions are involved in cognition in temporal lobe epilepsy (TLE). We retrospectively recruited 24 left-TLE and 15 right-TLE patients. Six thalamic subnuclei were segmented by magnetic resonance imaging, and then co-registered onto Positron emission tomography images. We calculated the asymmetrical indexes of the volumes and normalized standard uptake value ratio (SUVR) of the entire and individual thalamic subnuclei. The SUVR of ipsilateral subnuclei were extensively and prominently decreased compared with the volume loss. The posterior and medial subnuclei had persistently lower SUVR in both TLE cases. Processing speed is the cognitive function most related to the metabolic asymmetry. It negatively correlated with the metabolic asymmetrical indexes of subregions in left-TLE, while positively correlated with the subnuclei volume asymmetrical indexes in right-TLE. Epilepsy duration negatively correlated with the volume asymmetry of most thalamic subregions in left-TLE and the SUVR asymmetry of ventral and intralaminar subnuclei in right-TLE. Preserved metabolic activity of contralateral thalamic subregions is the key to maintain the processing speed in both TLEs. R-TLE had relatively preserved volume of the ipsilateral thalamic volume, while L-TLE had relatively decline of volume and metabolism in posterior subnucleus.

Findings of 2-fluoro-2-deoxy-d-glucose positron emission tomography in hemorrhoids.

BACKGROUND: Hemorrhoids are very common in adults. The data regarding the incidence of high 2-fluoro-2-deoxy-D: -glucose (FDG) uptake in hemorrhoids is incomplete. In this study, we evaluated FDG uptake in hemorrhoids and calculated the rate of high FDG uptake in these lesions. METHODS: One hundred and seventy six subjects who undertook whole body FDG-PET for health screening examination were investigated retrospectively. All patients had colonoscopy and 156 subjects were found to have hemorrhoids and 20 had no hemorrhoids. Quantitative analysis of FDG uptake in the anal region was performed by calculating the maximum standard uptake value (SUV(max)). RESULTS: The SUV(max) ranged from 1.8 to 4.1 (2.8 ± 0.6) for normal subjects and ranged from 1.4 to 8.3 (2.9 ± 0.8) for patients with hemorrhoids. No statistical difference was noted between these two groups using a Student's t-tests. If the highest SUV(max), which was 4.1 in normal subjects, was used as a cutoff, 5.1% (8/156) hemorrhoid patients had a SUV(max) greater than 4.1. CONCLUSION: Hemorrhoids can be one possible cause of focal high FDG uptake in the rectum.

Left-ventricular dyssynchrony in viable myocardium by myocardial perfusion SPECT is predictive of mechanical response to CRT.

OBJECTIVES: Gated myocardial perfusion SPECT (GMPS) provides a one-stop-shop evaluation for cardiac resynchronization therapy (CRT). However, conflicting results have been observed regarding whether the baseline left-ventricular (LV) mechanical dyssynchrony as assessed by phase analysis on GMPS was predictive of therapeutic response to CRT. Since dyssynchrony parameters by phase analysis spuriously increased by scarred myocardium, the purpose of this study was to explore the value of dyssynchrony after stripping off the scar region in correlation to mechanical response to CRT. METHODS: Forty-seven patients following standard indications for CRT received GMPS with phase analysis as pre-CRT evaluation. A decrease of end-systolic volume (ESV) > 15% on follow-up echocardiography after CRT was considered as a mechanical response to CRT. Myocardial regions with less than 50% of maximal activity on GMPS were considered as a scar. The phase standard deviation (PSD) and histogram bandwidth (BW) without or with stripping off scar were assessed by phase analysis of GMPS and were used for evaluation of LV dyssynchrony of all myocardium or only the viable myocardium, respectively. RESULTS: No significant difference was noted between mechanical responders (31 of 47 patients, 66%) and nonresponders ( 16 of 47 patients, 34%) for PSD (48.6° ± 19.4° vs 43.9° ± 20.7°, p = 0.46) and BW (225° ± 91.1° vs 163.5° ± 94.6°, p = 0.38) of the entire myocardium. However, responders had significantly larger PSD (40.5° ± 15.7° vs 30.5° ± 13.2°, p = 0.03) and borderlinely larger BW (215° ± 91.2° vs. 139.5° ± 78.2°, p = 0.05) than non-responders after stripping off scar. Logistic regression analysis showed that scar area and PSD after stripping off scar were independent predictors of mechanical response. CONCLUSIONS: Our result showed that LV dyssynchrony of the entire myocardium did not predict response to CRT. However, LV dyssynchrony only in the viable myocardium was a significant predictor of CRT mechanical response.

Change of Renal Gallium Uptake Correlated with Change of Inflammation Activity in Renal Pathology in Lupus Nephritis Patients.

BACKGROUND: Lupus nephritis (LN) often lead to end-stage renal disease in systemic lupus erythematosus patients. This study aimed to investigate the clinical application of renal gallium-67 scans for determining renal histological parameters in LN patients. METHODS: Between 2006 and 2018, 237 biopsy-proven and 35 repeat biopsies LN patients who underwent renal gallium scans before or after biopsy were included for analysis. The classification and scoring of LN were assessed according to the International Society of Nephrology/Renal Pathology Society. A delayed 48-h gallium scan was performed and interpreted by semiquantitative methods using left kidney/spine (K/S) ratio. The renal histological results were compared with gallium uptake. RESULTS: Out of 237 participants, 180 (76%) had proliferative LN. Baseline gallium left K/S ratio was significantly higher in class IV LN as compared to class III (median (interquartile range, IQR): 1.16 (1.0-1.3), 0.95 (0.9-1.1), respectively, p < 0.001). Furthermore, changes in gallium uptake between two biopsies were positively correlated with changes activity index (r = 0.357, p = 0.035), endocapillary hypercellularity (r = 0.385, p = 0.032), and neutrophils infiltration (r = 0.390, p = 0.030) in renal pathology. CONCLUSIONS: Renal gallium uptake is associated with active inflammation in LN. Changes in renal gallium uptake positively correlated with changes in activity index in renal pathology.

Exploiting Honokiol-induced ER stress CHOP activation inhibits the growth and metastasis of melanoma by suppressing the MITF and ß-catenin pathways.

There is increasing global incidence of highly metastatic melanoma and therapeutic strategies like those focusing on the downstream beta-catenin/MITF axis of invading melanoma cells are urgently needed. Targeting endoplasmic reticulum (ER) stress can promote cancer cell death and inhibit epithelial mesenchymal transition (EMT) in metastatic tumors. This study aimed to determine if Honokiol could promote ER stress-dependent apoptosis and regulate metastatic melanoma. The therapeutic efficacy of Honokiol was assessed using the highly metastatic melanoma xenograft mouse model for peritoneal metastasis and evaluated by computed tomography imaging. The ER stress marker, Calpain-10, delineated a novel proteolytic cleavage enzyme, while CHOP/GADD153-regulated apoptosis was used for gene silencing to determine the role of the ß-catenin/MITF axis in melanoma cells. The results showed that Honokiol effectively decreased peritoneal dissemination and organ metastasis via ER stress activation and EMT marker inhibition. Knockdown Calpain-10 or CHOP/GADD153 blocked all of the biological effects in Honokiol-induced ß-catenin/MITF cleavage, ERSE or TCF/LEF luciferase activity, and ß-catenin kinase activity. These findings suggest that Honokiol can significantly thwart the progression of highly metastatic melanoma using the ß-catenin/MITF axis via prompt Calpain-10 and CHOP/GADD153 regulated cascades.

Value of gallium-67 scanning in monitoring therapeutic effectiveness in a patient with relapsing polychondritis.

We present a 57-year-old man who had low-grade fever and painful, swollen and erythematous ears. Gallium-67 citrate scintigraphy (gallium scan) performed prior to the commencement of treatment showed increased gallium uptake in bilateral external ears, neck, mediastinum and bilateral pulmonary hili. The results of ultrasonography of both ears were compatible with the diagnosis of chondritis. The patient's clinical condition and laboratory data improved after a course of nonsteroidal anti-inflammatory drugs and steroids. Gallium scan performed after treatment showed a diminished uptake in the external ears, neck, and mediastinum. Gallium scintigraphy is a valuable tool for evaluating inflammatory activity and monitoring therapeutic response in patients with relapsing polychondritis.

Dual-phase 99mTc-MIBI parathyroid imaging reveals synchronous parathyroid adenoma and papillary thyroid carcinoma: a case report.

The possibility of a coincidental appearance of hyperparathyroidism and thyroid cancer is not often considered because of its low incidence. Here, we present a case of a 49-year-old woman with a parathyroid adenoma coexisting with two sites of papillary thyroid carcinoma. Dual-phase 99mTc-methoxyisobutylisonitrile (MIBI) parathyroid imaging before the operation correctly visualized the site of the parathyroid adenoma. In addition, two papillary thyroid carcinomas showed faint uptake of 99mTc-MIBI on delayed image. Total thyroidectomy and parathyroidectomy of a solitary parathyroid adenoma were performed. The patient subsequently underwent radioiodine-131 ablation and was treated with T4 suppression. This case illustrates the need for clinical awareness of concomitant hyperparathyroidism and thyroid cancer. Dual-phase 99mTc- MIBI parathyroid imaging may be useful for detecting indolent thyroid cancer before it becomes a distinct disease.

Reducing renal uptake of 111In-DOTATOC: a comparison among various basic amino acids.

PURPOSE: Several studies have reported significant renal toxicity after the use of a high dose of 90Y-DOTATOC. Thus, renal protection is necessary in treatments with 90Y-DOTA Tyr3-octreotide (DOTATOC). The infusion of certain positively charged amino acids has been shown to effectively reduce renal uptake of DOTATOC. In this study, we compared the effectiveness of three kinds of amino acids, D-lysine (lysine), L-arginine (arginine) and histidine, on renal protection in healthy rats and tried to determine which one was the most effective. METHODS: Twenty SD healthy male rats were divided into 4 groups: lysine, histidine, arginine, and control. The rats were injected with a dose of 400 mg/kg of amino acid or 2 ml of phosphate-buffered saline (PBS) (as control) intraperitoneally. All rats were sacrificed at 4 hrs after the injection of 1 MBq 111In-DOTATOC. Samples of the kidney were taken and weighed carefully. The counts of radioactivity were measured by a gamma counter and renal concentrations were calculated and expressed as percent injected dose per gram (% ID/g). RESULTS: The renal uptake of 111In-DOTATOC was significantly lower for all three kinds of amino acids when compared to the control group. The renal uptake of 111In-DOTATOC in the lysine group was significantly lower than those in the histidine and arginine groups. The renal uptake of 111In-DOTATOC in the histidine group was lower than that in the arginine group, but no statistical difference was noted. CONCLUSION: Among these three amino acids, lysine had the best reduction rate of renal uptake of DOTATOC. Histidine was more effective than arginine but no statistical difference was noted.

Collar Osteophytes Mimicking Osteonecrosis in Planar Bone Scintigraphy and Usefulness of SPECT/CT Images.

The use of prednisolone is one major risk factor for osteonecrosis in patients with systemic lupus erythematosus. Bone scintigraphy can be a diagnostic tool for early diagnosis. We present a case who had collar osteophytes at the bilateral femoral heads, which mimicked osteonecrosis in the planar bone scintigram. An SPECT/CT scan avoided this pitfall and increased the diagnostic accuracy for osteonecrosis.

Application of Fluorine-18-Deoxyglucose Positron Emission Tomography and Gallium Scan for Assessment in a Patient With Adult-Onset Still's Disease.

A 53-year-old female patient suffered from pain in almost her entire body, particularly the joints. Chest computed tomography revealed multiple lymphadenopathies over cervical, mediastinal, and axillary areas. A fluorine-18-deoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) revealed increased FDG uptake in many lymph nodes and the spleen. Lymphoma was suspected. However, the result of a biopsy showed no malignancy, and the gallium-67 citrate scan showed no gallium-avid tumor throughout the whole body. Adult-onset Still's disease was diagnosed and the patient responded well to steroid therapy. The follow-up PET/CT six months later showed complete remission of the FDG-avid lesions seen in the previous PET/CT. Our study suggests that FDG PET/CT combined with gallium-67 scan may be helpful in diagnosing patients with adult-onset Still's disease. In addition, the use of FDG PET/CT alone may be useful for the evaluation of disease distribution, disease activity, and therapeutic response.

Absolute Quantitative Evaluation of 67Ga Scintigraphy in Lupus Nephritis.

PURPOSE: Renal biopsy is crucial for management of lupus nephritis. However, it is invasive and can cause bleeding and infection. In our previous study, we developed a semiquantitative method for gallium renal imaging and demonstrated a good correlation between the left kidney-to-spine ratio (K/S ratio) and the results of renal biopsy. However, the accuracy of left K/S ratio is compromised by the variation of spinal gallium uptake, especially in patients with extraordinarily high or low gallium uptakes in the spine. In this study, we developed an absolute quantitative method and compared the results of quantitative gallium images, semiquantitative gallium images, visual methods, and renal biopsies. METHODS: Thirty-four patients with lupus nephritis were enrolled and underwent renal biopsy to determine activity index (AI) and chronicity index. A delayed 48-hour gallium scan was also performed and interpreted by visual, semiquantitative, and absolute quantitative methods. For absolute quantitative analysis, a standard solution with activities of approximately 555 KBq (15 µCi) was prepared and poured into a 5-mL tube, which was placed close to the patient. ROIs were drawn around the outer edge of the left kidney as well as around the outer edges of the standard. A kidney uptake index (KUI) was calculated, and the results were compared with K/S ratio, visual grading, and renal biopsies. RESULTS: Kidney uptake index had the best correlation with AI among the 3 methods using Spearman rank correlation test. The Spearman R values were 0.78, 0.71, and 0.61 for KUI, K/S ratio and visual grading, respectively. Chronicity index did not correlate well with the results of any of the 3 methods. In addition, AI was significantly higher in patients with a KUI equal to or greater than 1.5, when compared with patients with a KUI lower than 1.5 (P = 0.00001 by Mann-Whitney U test). Using a K/S ratio of 0.95 as a cutoff value, AI also showed a statistically significant difference with P = 0.0001. When a visual grading of 2 was used as a cutoff value, P = 0.0008. The difference in AI was most significant when the statistical value was based on the KUI. CONCLUSIONS: The KUI showed better correlation with the results of renal biopsy than the K/S ratio and the visual grading. We suggest that the KUI from the absolute quantitative renal gallium scintigraphy may be a useful parameter for evaluating the disease activity in lupus nephritis.

LV Dyssynchrony Is Helpful in Predicting Ventricular Arrhythmia in Ischemic Cardiomyopathy After Cardiac Resynchronization Therapy: A Preliminary Study.

For patients with coronary artery disease, larger scar burdens are associated with higher risk of ventricular arrhythmia. Left ventricular (LV) dyssynchrony is associated with increased risk of sudden cardiac death in patients with heart failure. The purpose of this study was to assess the values of LV dyssynchrony and myocardial scar assessed by myocardial perfusion SPECT (MPS) in predicting the development of ventricular arrhythmia in ischemic cardiomyopathy. Twenty-two patients (16 males, mean age: 66 ±â€Š13) with irreversible ischemic cardiomyopathy received cardiac resynchronization therapy (CRT) for at least 12 months were enrolled for MPS. Quantitative parameters, including LV dyssynchrony with phase standard deviation (phase SD) and bandwidth, left ventricular ejection fraction (LVEF), and scar (% of total areas), were generated by Emory Cardiac Toolbox. Ventricular tachycardia (VT) and ventricular fibrillation (VF) recorded in the CRT device during follow-up were used as the reference standard of diagnosing ventricular arrhythmia. Stepwise logistic regression analysis was performed for determining the independent predictors of VT/VF and receiver operating characteristic (ROC) curve analysis was used for generating the optimal cut-off values for predicting VT/VF. Nine (41%) of the 22 patients developed VT/VF during the follow-up periods. Patients with VT/VF had significantly lower LVEF, larger scar, larger phase SD, and larger bandwidth (all P < 0.05). Logistic regression analysis showed LVEF and bandwidth were independent predictors of VT/VF. ROC curve analysis showed the areas under the curves were 0.71 and 0.83 for LVEF and bandwidth, respectively. The optimal cut-off values were <36% and > 139° for LVEF and bandwidth, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 39%, 53%, and 100%, respectively, for LVEF; and were 78%, 92%, 88%, and 86%, respectively, for bandwidth. LV dyssynchrony as assessed by phase analysis of MPS is helpful for predicting ventricular arrhythmia in ischemic cardiomyopathy after CRT. Further implantation of defibrillator may be considered for those patients with bandwidth >139°.

Relationship of myocardial substrate characteristics as assessed by myocardial perfusion imaging and cardiac reverse remodeling levels after cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) can provide cardiac reverse remodeling (RR), which may include mechanical reverse remodeling (MRR) and/or electrical reverse remodeling (ERR). However, uncoupling of MRR and ERR is not uncommon, and the underlying mechanisms are not clear. This study aimed to evaluate the relationship of myocardial substrate characteristics as assessed by myocardial perfusion imaging (MPI) and cardiac RR post-CRT. MATERIALS AND METHODS: Forty-one patients (26 men, mean age 66 ± 10 years) with heart failure received CRT for at least 12 months were assigned to three groups according to their levels of RR: I, MRR + ERR (ESV reduced ≥15 % and intrinsic QRS duration reduced ≥10 ms); II, MRR only (ESV reduced ≥15 %); and III, non-responder (the others). All the patients also underwent MPI under transient CRT-off to evaluate the intrinsic myocardial substrates, including myocardial scar, LV volumes and function, systolic dyssynchrony, and activation sequences. In addition, ventricular tachycardia (VT) and ventricular fibrillation (VF) detected by the CRT devices during follow-up periods were also recorded. RESULTS: Quantitative analysis of MPI showed that there were significant differences for scar burden [15.9 ± 9.5, 26.8 ± 16.1, and 45.6 ± 15.1 % for group I (n = 15), II (n = 16), and III (n = 10), respectively, p < 0.001], EDV (136.6 ± 64.9, 221.6 ± 123.9, and 351.8 ± 216.3 ml, p = 0.002), ESV (82.6 ± 59.8, 172.3 ± 117.2, and 293.3 ± 209.6 ml, p = 0.001), LVEF (44.9 ± 15.0, 25.6 ± 10.9, and 21.5 ± 11.7 %, p < 0.001), systolic phase SD (23.4° ± 10.3°, 36.0° ± 16.2°, and 57.0° ± 22.2°, p < 0.001), and bandwidth (72.5° ± 31.1°, 113.4° ± 56.4°, and 199.1° ± 90.1°, p < 0.001). Myocardial scar interfered with the normal propagation of mechanical activation, resulting in heterogeneous activation sequences. Compared with group II (MRR only), group I (ERR + MRR) had significantly less initial activation segments (1.9 ± 1.0 vs. 2.6 ± 0.7, p < 0.05) and shorter maximal contraction delay (46.9° ± 12.9° vs. 58.8° ± 18.5°, p < 0.05). During the periods of follow-up, 21 patients developed VT/VF, including only 1 patient (1 VT) in group I (6.7 %), 8 patients (7 VT and 1 VF) in group II (50 %), and 9 patients (7 VT and 5 VF) in group III (90 %). CONCLUSION: The characteristics of myocardial substrates as assessed by MPI differed significantly between different levels of cardiac RR post-CRT. Myocardial scar played an important role in the development of ERR. Different cardiac RR levels contributed to different incidences of ventricular arrhythmia, and the combination of ERR and MRR provided highest anti-arrhythmic effects.

Comparison of Tc-99m sestamibi and F-18 FDG-PET in the assessment of multiple myeloma.

BACKGROUND: Tc-99m methoxy-isobutyl-isonitrile (MIBI) has been reported to be a useful tracer in patients with multiple myeloma (MM). Few articles have reported the potential value of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in the evaluation of MM. Therefore, the purpose of this study was to compare the diagnostic abilities of the MIBI scan and the FDG-PET scan in the evaluation of MM. MATERIALS AND METHODS: Twelve patients with MM were included. All patients received a radiological skeletal survey, MIBI scan and FDG-PET scan. RESULTS: Thirty-four lesions (19 soft tissue lesions and 15 skeletal lesions) plus 5 cases of bone marrow involvement were detected. The conventional skeletal X-ray survey detected 4 soft tissue lesions (21.1%), 12 skeletal lesions (80%), but no bone marrow involvement (0%). The MIBI scan found 4 cases of bone marrow involvement (80%), 13 soft tissue lesions (68.4%) and 12 skeletal lesions (80%). The PET scan detected 5 cases of bone marrow involvement (100%), 17 soft tissue lesions (89.5%) and 14 skeletal lesions (93.3%). CONCLUSION: Both the MIBI and the FDG-PET scans are useful in the evaluation of patients with MM. However, FDG-PET can detect more lesions than the MIBI scan in patients with MM.