Establishment of CT diagnostic reference levels (DRLs) for a Singapore healthcare cluster.

INTRODUCTION: The use of computed tomography (CT) in healthcare institutions has increased rapidly in recent years. The Singapore Health Services (SingHealth) cluster of healthcare institutions has taken the first step in establishing a local cluster-wide CT Diagnostic Reference Levels (DRL) in Singapore. CT dose data from each institution were collected through two primary dosimetry metrics: volume CT dose index (CTDIvol measured in mGy) and dose-length product (DLP measured in mGy.cm). METHODS: Data from 19 CT scanners in seven institutions under one of Singapore healthcare cluster were retrospectively collected and analysed. The five common adult CT examinations analysed were CT Brain (non-contrast enhanced), CT Chest (IV contrast enhanced), CT Kidney-Ureter-Bladder (CT KUB, non-contrast enhanced), CT Pulmonary Angiogram (CT PA, IV contrast enhanced) and CT Abdomen-Pelvis (CT AP, IV contrast enhanced, single phase). Median CTDIvol and DLP values for the five CT examinations from each institution were derived, with the cluster DRLs determined as the 75th percentile of the distribution of the institution median dose values. RESULTS: A total of 2413 dose data points were collected over a six-month period from June to November 2020. The cluster CT DRLs for the five CT examinations were determined to be 47 mGy and 820 mGy.cm for CT Brain, 5.4 mGy and 225 mGy.cm for CT Chest, 6.7 mGy and 248 mGy.cm for CT PA, 4.6 mGy and 190 mGy.cm for CT KUB and 6.9 mGy and 349 mGy.cm for CT AP. CONCLUSION: The establishment of the cluster CT DRLs provided individual institutions with a better understanding if their CT doses are unusually high or low, while emphasising that these DRLs are not meant as hard dose limits or constraints to follow strictly.

Postnatal women's breastfeeding beliefs, practices, and support during the COVID-19 pandemic: a cross-sectional comparative study across five countries.

BACKGROUND: Women with COVID-19 experienced numerous concerns and doubts about the safety of breastfeeding their babies, and lack of support may have impacted breastfeeding practices. This study aims to compare breastfeeding beliefs, practices, and contact with healthcare professionals regarding the level of postnatal feeding support provided during the COVID-19 pandemic in Brazil, South Korea, Taiwan, Thailand, and the United Kingdom. METHODS: A multi-country cross-sectional study was conducted with postnatal women in five countries. Women up to six months postpartum were invited to complete an online survey concerning the transmission of preventative measures, beliefs toward breastfeeding, infant feeding practices in the last 24 hours and experiences of postnatal infant feeding support between July to November 2021. Bivariate and multivariate analyses were performed to identify the association. RESULTS: Of the 3,253 eligible responses received, 39.5% of children were aged between one and two months, but in Taiwan (36%) and South Korea (42.8%) they were between three and four months. The mean of the belief score was significantly different among countries (p < 0.0001). Women in Brazil and the UK had a higher rate of breastfeeding at the breast (90.7% and 85.4%, respectively) compared to the three Asian countries (p < 0.0001) while feeding with expressed breastmilk in Thailand (59.9%), Taiwan (52.6%), and South Korea (50.4%) was higher than the others (p < 0.0001). Brazil and UK mothers (mean = 16.0 and 14.5 respectively) had a higher mean score for belief toward breastfeeding during the COVID-19 than the others. These results are inversely associated with breastfeeding but positively related to formula feeding practice. Postnatal feeding support during the COVID-19 pandemic was mainly provided by healthcare professionals (67.1%) and peers / family through face-to-face personal contact (51.6%) in all countries. CONCLUSION: Some differences were found in breastfeeding beliefs during the COVID-19 pandemic in Asian countries. A positive breastfeeding belief was associated with the practice of breastfeeding at the breast. Women from all countries received postpartum infant feeding support from health professionals and peers / family through personal contacts. Governments need to emphasize and disseminate the importance of breastfeeding safety, especially in Asian countries.

SOX9+ enthesis cells are associated with spinal ankylosis in ankylosing spondylitis.

OBJECTIVE: Although cartilage degeneration and invasion of the subchondral bone plate in entheseal lesion has been considered to consequently lead bony ankylosis in ankylosing spondylitis (AS), no evident mechanisms are known. DESIGN: To identify histopathological and physiological changes in enthesitis-related ankylosis in AS, we performed molecular characterization of transcription factors and surface markers, and transcriptome analysis with human tissues. Entheseal tissue containing subchondral bone was obtained from the facet joints of 9 patients with AS and 10 disease controls, and assessed by using differential staining techniques. Enthesis cells were isolated, characterized, stimulated with TNF and/or IL-17A, and analysed by cell-based experimental tools. RESULTS: We found diffusely distributed granular tissue and cartilage in the subchondral bone in AS. Co-expression of SOX9, a specific transcription factor in cartilage, and matrix metalloproteinase 13 (MMP13) was found in the granular tissues within the subchondral bone from AS patients. Intriguingly, SOX9 expression was significantly higher in AS enthesis cells than controls and correlated with TNFR1 and IL-17RA expressions, which is important for high reactivity to TNF and IL-17A cytokines. Co-stimulation by TNF and IL-17A resulted in accelerated mineralization/calcification features, and increased OCN expression in AS enthesis cells. Furthermore, SOX9 overexpression in enthesis leads to promoting mineralization feature by TNF and IL-17A stimuli. Finally, OCN expression is elevated in the destructive enthesis of advanced AS. CONCLUSION: These findings provide insight into the links between inflammation and the mineralization of entheseal tissue as the initiation of spinal ankylosis, emphasizing the importance of SOX9+ enthesis cells.

Sequence and Observer Variability in Gadoxectic Acid-Enhanced MRI Lesion Measurements in Hepatocellular Carcinoma.

RATIONALE AND OBJECTIVES: The purpose of the study was to investigate interobserver and intersequence variability in measuring hepatocellular carcinoma on magnetic resonance imaging (MRI). METHODS AND MATERIALS: Twenty treatment-naïve lesions on Gadoxetic Acid enhanced MRI scans from 20 patients were retrospectively measured by six reviewers with different levels of experience, twice, six weeks apart, on eight different MRI sequences, in randomized order. The sequences include arterial, hepatobiliary, transitional, portal venous, T2, and diffusion weighted images. The single longest diameter (SLD) and longest diameter perpendicular to the longest overall diameter were measured on axial images and products of diameters calculated in accordance to response evaluation criteria in solid tumors v1.1 and World Health Organization response criteria respectively. Lesion-wise intraclass correlation coefficients were used to estimate measurement agreement. RESULTS: All intraclass correlation coefficients were greater than 0.95. No substantive differences between SLD and products of diameters metrics. Means (∼2.8 mm, SLD) and standard deviations (∼2 mm, SLD) were similar across sequences and observers. Similarly, pairwise comparison between observers grouped by experience showed statistically significant differences, but the effect size was minor (∼2 mm). Arterial and HPB-weighted images had similar mean dimensions (2.76 cm) while the smallest mean was in the transitional phase (2.62 cm). A lesion was not measured on 140 occasions (7%), mostly in ADC. CONCLUSION: There is high interobserver and intersequence reliability despite small differences between observers based on experience level. Our results suggest that accurate measurements can be made on arterial phase despite the possibility of indistinct margins. Lesions, however, are more likely to be missed on diffusion-related sequences.

Urinary vitamin D-binding protein, a novel biomarker for lupus nephritis, predicts the development of proteinuric flare.

Lupus nephritis (LN) is a major complication of systemic lupus erythematosus (SLE). Conventional biomarkers for assessing renal disease activity are imperfect in predicting clinical outcomes associated with LN. The aim of this study is to identify urinary protein biomarkers that reliably reflect the disease activity or predict clinical outcomes. A quantitative proteomic analysis was performed to identify protein biomarker candidates that can differentiate between SLE patients with and without LN. Selected biomarker candidates were further verified by enzyme-linked immunosorbent assay using urine samples from a larger cohort of SLE patients ( n = 121) to investigate their predictive values for LN activity measure. Furthermore, the association between urinary levels of a selected panel of potential biomarkers and prognosis of LN was assessed with a four-year follow-up study of renal outcomes. Urinary vitamin D-binding protein (VDBP), transthyretin (TTR), retinol binding protein 4 (RBP4), and prostaglandin D synthase (PTGDS) were significantly elevated in SLE patients with LN, especially in patients with active LN ( n = 21). Among them, VDBP well correlated with severity of proteinuria (rho = 0.661, p < 0.001) and renal SLE Disease Activity Index (renal SLEDAI) (rho = 0.520, p < 0.001). In the four-year follow-up, VDBP was a significant risk factor (hazard ratio 9.627, 95% confidence interval 1.698 to 54.571, p = 0.011) for the development of proteinuric flare in SLE patients without proteinuria ( n = 100) after adjustments for multiple confounders. Urinary VDBP correlated with proteinuria and renal SLEDAI, and predicted the development of proteinuria.

The emerging roles of functional imaging in ovarian cancer with peritoneal carcinomatosis.

This article reviews the emerging roles of functional imaging in the assessment of peritoneal carcinomatosis in ovarian cancer, focusing on the use of diffusion-weighted magnetic resonance imaging (DW-MRI) and 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography combined with computed tomography (PET-CT), their advantages and shortcomings as well as the added-value over conventional imaging.

Physical activity, sedentary behaviour, and psychosocial well-being among young South Korean children.

OBJECTIVE: To examine associations between television (TV) viewing, reading, physical activity (PA), and psychosocial well-being among a representative sample of young South Korean children aged 0-5 years. METHODS: Findings are based on 1,774 children who participated in the Korea Children and Youth Survey. All measures were questionnaire-derived. Psychosocial well-being included social, interactive, and emotional skills (α = .7-.9), and the top quartile denoted high psychosocial well-being. Multiple logistic regressions were performed to examine relationships after controlling for several confounders. RESULTS: Compared to children who participated in PA for <1 hr/week, those who participated in PA for 1- <3 hr/week were more likely to show high emotional skills (odds ratio [OR]: 1.40, 95% confidence interval [CI] [1.02, 1.93]), and those who participated ≥3 hr/week were more likely to show high social (OR: 2.01, 95% CI [1.45, 2.78]) and interactive skills (OR: 1.39, 95% CI [1.01, 1.92]). During weekdays, children who read 1- <3 hr/day and ≥3 hr/day, compared to <1 hr/day, were more likely to show high social (OR: 1.61, 95% CI [1.20, 2.16] and OR: 2.47, 95% CI [1.31, 4.67]) and emotional skills (OR: 1.57, 95% CI [1.16, 2.13] and OR: 2.58, 95% CI [1.34, 4.98]). In addition, children who read 1- <3 hr/day, compared to <1 hr/day, were more likely to show high interactive skills (OR: 1.44, 95% CI [1.08, 1.92]). Similar findings for reading on weekends were observed. TV viewing was not associated with social skills or interactive skills. TV viewing for 1- <3 hr/day, compared to <1 hr/day, was associated with increased odds of high emotional skills (OR: 1.71, 95% CI [1.28, 2.27] on weekdays; OR: 1.90, 95% CI [1.39, 2.61] on weekends). CONCLUSION: PA and reading primarily showed favourable associations with psychosocial well-being, whereas TV viewing did not; thus, PA or reading may be a better option over TV viewing for optimal psychosocial well-being among young South Korean children. These findings should be confirmed with stronger study designs.

Effect of an obesity prevention program focused on motivating environments in childhood: a school-based prospective study.

BACKGROUND/OBJECTIVES: There has been an increasing global recognition of the need for effective strategies to prevent and control childhood obesity. In this study, we aimed to identify the effectiveness of an obesity prevention program focused on motivating environments in school. SUBJECTS/METHODS: In this school-based, prospective, quasi-experimental study, we enrolled three elementary (fourth graders) and two middle (seventh graders) schools located in Chungju, Korea. We assigned three of the schools to the intervention group and two schools to the control group. The intervention group received 1 year of environmental intervention. Diet- and exercise-related educational video content was provided by internet protocol television services during rest time, and various design materials were painted along the school staircase and hallway to encourage physical activities. Overweight and obese students were recommended to join the summer vacation obesity care program. RESULTS: The final number of total participants was 768 (control 350 and intervention 418). After 1 year of follow-up, there was no significant difference in the overweight/obesity incidence rates and remission rates between the two groups. However, the intervention group showed a greater decrease in the body mass index (BMI) z-score (-0.11 (95% confidence interval (CI) -0.16 to -0.06), P<0.001), increase in height (1.1 cm (95% CI 0.8 to 1.4), P<0.001), reduction of body fat, and increase in muscle mass compared with the control group. In addition, blood pressure (BP) was significantly reduced, and significant improvement in physical fitness followed. In subgroup analysis, students of normal weight, boys and younger participants showed the most beneficial results in weight-related outcomes. In addition, the BP reduction was more pronounced in the higher BMI group, boys and older children. CONCLUSIONS: A simple environmental intervention could effectively influence children. By adding to previously studied strategies, we can develop a more effective obesity prevention program for children.

Triglycerides/glucose index is a useful surrogate marker of insulin resistance among adolescents.

OBJECTIVES: Our aim was to investigate the association between the triglycerides/glucose index (TyG index) and the homeostasis model assessment-estimated insulin resistance (HOMA-IR) in the prediction of insulin resistance (IR) among adolescents. METHODS: We conducted a cross-sectional study among 221 Korean adolescents (168 males and 53 females aged 9-13 years) from May to June 2014 in Chung-ju city. The TyG index was calculated as ln [triglycerides (mg dl-1) × fasting glucose (mg dl-1)/2]. IR was defined using HOMA-IR >95th percentile for age and sex. RESULTS: In the IR group, weight, body mass index (BMI), waist circumference, body fat, fasting insulin, fasting plasma glucose, triglyceride levels and triglycerides/high-density lipoprotein cholesterol (TG/HDL-C) were significantly higher than that in the non-IR group. The TG index was significantly different between the IR group (n=22) and non-IR group (n=199), at 8.43±0.45 and 8.05±0.41, respectively (P<0.001). The TyG index was well correlated with HOMA-IR (r=0.41; P<0.001) and showed a strong positive association with TG/HDL-C (r=0.84; P<0.001). The cut-off of the TyG index for diagnosis of insulin resistance was 8.18. CONCLUSIONS: The TyG index is a simple, cost-effective surrogate marker of insulin resistance among adolescents compared with HOMA-IR.

Foxp3 is a key downstream regulator of p53-mediated cellular senescence.

The downstream events and target genes of p53 in the process of senescence are not fully understood. Here, we report a novel function of the forkhead transcription factor Foxp3, which is a key player in mediating T-cell inhibitory functions, in p53-mediated cellular senescence. The overexpression of Foxp3 in mouse embryonic fibroblasts (MEFs) accelerates senescence, whereas Foxp3 knockdown leads to escape from p53-mediated senescence in p53-expressing MEFs. Consistent with these results, Foxp3 expression resulted in the induction of senescence in epithelial cancer cells, including MCF7 and HCT116 cells. Foxp3 overexpression also increased the intracellular levels of reactive oxygen species (ROS). The ROS inhibitor N-acetyl-l-cysteine rescued cells from Foxp3-expression-induced senescence. Furthermore, the elevated ROS levels that accompanied Foxp3 overexpression were paralleled by an increase in p21 expression. Knockdown of p21 in Foxp3-expressing MEFs abrogated the Foxp3-dependent increase in ROS levels, indicating that Foxp3 acts through the induction of p21 and the subsequent ROS elevation to trigger senescence. Collectively, these results suggest that Foxp3 is a downstream target of p53 that is sufficient to induce p21 expression, ROS production and p53-mediated senescence.

Contrast induced nephropathy in vascular surgery.

Contrast induced nephropathy (CIN) is traditionally associated with outpatient imaging studies. More recently, patients afflicted with vascular pathologies are increasingly undergoing endovascular treatments that require the use of iodinated contrast media (CM) agents, thus placing them as risk of developing CIN. As perioperative physicians, anaesthetists should be aware of the risk factors and measures that might minimize acute kidney injury caused by CM. This review evaluates recent data regarding preventive measures against CIN and where possible, places the evidence in the context of the patient receiving endovascular surgical treatment. Measures including the use of peri-procedural hydration, N-acetylcysteine, statins, remote ischaemic preconditioning, renal vasodilators and renal replacement therapy and the use of alternatives to iodinated contrast agents are discussed. It should be noted that most of the available data regarding CIN are from non-surgical patients.

Eicosapentaenoic acid ameliorates hyperglycemia in high-fat diet-sensitive diabetes mice in conjunction with restoration of hypoadiponectinemia.

BACKGROUND/OBJECTIVE: Eicosapentaenoic acid (EPA) exerts pleiotropic effects on metabolic disorders such as atherosclerosis and dyslipidemia, but its effectiveness in the treatment of type 2 diabetes mellitus remains controversial. METHODS: We examined the antidiabetic effect of EPA in insulin receptor mutant (Insr(P1195L/+)) mice that exhibit high-fat diet (HFD)-dependent hyperglycemia. RESULTS: EPA supplementation was found to alleviate hyperglycemia of Insr(P1195L/+) mice fed HFD (Insr(P1195L/+)/HFD mice), which was accompanied by amelioration of increased gluconeogenesis and impaired insulin signaling, as assessed by glucose-6-phosphatase (G6pc) expression on refeeding and insulin-induced phosphorylation of Akt in the liver, respectively. We found that serum levels of adiponectin, the antidiabetic adipokine, were decreased by HFD along with the body weight gain in Insr(P1195L/+) mice but not in wild-type mice, suggesting that Insr(P1195L/+) mice are prone to hypoadiponectinemia in response to obesity. Interestingly, the blood glucose levels of Insr(P1195L/+) mice were in reverse proportion to their serum adiponectin levels and EPA supplementation ameliorated their hyperglycemia in conjunction with the restoration of hypoadiponectinemia. CONCLUSIONS: EPA exerts an antidiabetic effect in Insr(P1195L/+)/HFD mice, an HFD-sensitive, insulin-resistant animal model, possibly through its action against hypoadiponectinemia.

Malva verticillata seed extracts upregulate the Wnt pathway in human dermal papilla cells.

OBJECTIVE: Mesenchymal-epithelial interactions are important in controlling hair growth and the hair cycle. The ß-catenin pathway of dermal papilla cells (DPCs) plays a pivotal role in morphogenesis and normal regeneration of hair follicles. Deletion of ß-catenin in the dermal papilla reduces proliferation of the hair follicle progenitor cells that generate the hair shaft and induces an early onset of the catagen phase. In this study, a modulator of the Wnt/ß-catenin activity was studied in oriental herb extracts on cultured human DPCs. METHODS: The effect of Malva verticillata (M. verticillata) seeds on human DPCs was investigated by a Wnt/ß-catenin reporter activity assay system (ß-catenin-TCF/LEF reporter gene) and cell proliferation analysis. The synthesis of the factors related to hair growth and cycling was measured at both the mRNA and the protein level by semi-quantitative PCR and Western blot analysis, respectively. RESULTS: An extract from M. verticillata seeds increased Wnt reporter activity in a concentration-dependent manner and also led to increased ß-catenin levels in cultured human DPCs. Myristoleic acid, identified as an effective compound of M. verticillata seeds, stimulated the proliferation of DPCs in a dose-dependent manner and increased transcription levels of the downstream targets: IGF-1, KGF, VEGF and HGF. Myristoleic acid also enhanced the phosphorylation of MAPKs (Akt and p38). CONCLUSION: Overall, the data suggest that this extract of M. verticillata seeds could be a good candidate for treating hair loss by modulating the Wnt/ß-catenin pathway in DPCs.

Palmitate induces ER calcium depletion and apoptosis in mouse podocytes subsequent to mitochondrial oxidative stress.

Pathologic alterations in podocytes lead to failure of an essential component of the glomerular filtration barrier and proteinuria in chronic kidney diseases. Elevated levels of saturated free fatty acid (FFA) are harmful to various tissues, implemented in the progression of diabetes and its complications such as proteinuria in diabetic nephropathy. Here, we investigated the molecular mechanism of palmitate cytotoxicity in cultured mouse podocytes. Incubation with palmitate dose-dependently increased cytosolic and mitochondrial reactive oxygen species, depolarized the mitochondrial membrane potential, impaired ATP synthesis and elicited apoptotic cell death. Palmitate not only evoked mitochondrial fragmentation but also caused marked dilation of the endoplasmic reticulum (ER). Consistently, palmitate upregulated ER stress proteins, oligomerized stromal interaction molecule 1 (STIM1) in the subplasmalemmal ER membrane, abolished the cyclopiazonic acid-induced cytosolic Ca(2+) increase due to depletion of luminal ER Ca(2+). Palmitate-induced ER Ca(2+) depletion and cytotoxicity were blocked by a selective inhibitor of the fatty-acid transporter FAT/CD36. Loss of the ER Ca(2+) pool induced by palmitate was reverted by the phospholipase C (PLC) inhibitor edelfosine. Palmitate-dependent activation of PLC was further demonstrated by following cytosolic translocation of the pleckstrin homology domain of PLC in palmitate-treated podocytes. An inhibitor of diacylglycerol (DAG) kinase, which elevates cytosolic DAG, strongly promoted ER Ca(2+) depletion by low-dose palmitate. GF109203X, a PKC inhibitor, partially prevented palmitate-induced ER Ca(2+) loss. Remarkably, the mitochondrial antioxidant mitoTEMPO inhibited palmitate-induced PLC activation, ER Ca(2+) depletion and cytotoxicity. Palmitate elicited cytoskeletal changes in podocytes and increased albumin permeability, which was also blocked by mitoTEMPO. These data suggest that oxidative stress caused by saturated FFA leads to mitochondrial dysfunction and ER Ca(2+) depletion through FAT/CD36 and PLC signaling, possibly contributing to podocyte injury.

Novel small molecules disrupting Hec1/Nek2 interaction ablate tumor progression by triggering Nek2 degradation through a death-trap mechanism.

Hec1 (highly expressed in cancer 1) or Nek2 (NIMA-related kinase 2) is often overexpressed in cancers with poor prognosis. Both are critical mitotic regulators, and phosphorylation of Hec1 S165 by Nek2 is required for proper chromosome segregation. Therefore, inactivation of Hec1 and Nek2 by targeting their interaction with small molecules represents an ideal strategy for tackling these types of cancers. Here we showed that new derivatives of INH (inhibitor for Nek2 and Hec1 binding) bind to Hec1 at amino acids 394-408 on W395, L399 and K400 residues, effectively blocking Hec1 phosphorylation on S165 by Nek2, and killing cancer cells at the nanomolar range. Mechanistically, the D-box (destruction-box) region of Nek2 specifically binds to Hec1 at amino acids 408-422, immediately adjacent to the INH binding motif. Subsequent binding of Nek2 to INH-bound Hec1 triggered proteasome-mediated Nek2 degradation, whereas the Hec1 binding defective Nek2 mutant, Nek2 R361L, resisted INH-induced Nek2 degradation. This finding unveils a novel drug-action mechanism where the binding of INHs to Hec1 forms a virtual death-trap to trigger Nek2 degradation and eventually cell death. Furthermore, analysis of the gene expression profiles of breast cancer patient samples revealed that co-elevated expressions of Hec1 and Nek2 correlated with the shortest survival. Treatment of mice with this kind of tumor with INHs significantly suppressed tumor growth without obvious toxicity. Taken together, the new INH derivatives are suitable for translation into clinical application.

Baseline MRA predicts the treatment response to vasodilator udenafil in patients with secondary Raynaud's phenomenon.

OBJECTIVES: High-resolution MR angiography (HR-MRA) demonstrates blood flow in the digital arteries, which correlates with the severity of Raynaud's phenomenon (RP). This study investigates whether baseline HR-MRA of the hand can predict the treatment response to udenafil, a new PDE5-inhibitor, in patients with secondary RP. METHODS: Baseline MRA and Doppler ultrasound were obtained in 12 patients with secondary RP. The patients were treated with udenafil 100 mg/day for 4 weeks and changes in blood flow were measured. Blood flow on MRA was scored on a 4-point scale: 0, no visible flow; 1, visible flow to the proximal phalanx; 2, to the middle phalanx; and 3, to the distal phalanx. Peak systolic velocity (PSV) was measured to determine blood flow. Paired t-test and ANOVA were used to determine the treatment response of the different MRA scores. RESULTS: On baseline MRA, 53.3% of digital arteries had an MRA score of 0, 25.8% MRA score of 1, 9.2% MRA score of 2, and 11.6% MRA score of 3. Overall, 4-week udenafil treatment improved digital flow (p<0.05) in all MRA scores. Digital arteries with MRA score 2 showed the best response with improvement in PSV by 14.5 mm/sec (p<0.01), whereas improvement in arteries of MRA scores 1 and 3 were not better than an MRA score of 0 (all, p>0.05). CONCLUSIONS: Digital arteries with moderate blood flow observed on MRA respond best to treatment with udenalfil. Therefore, baseline MRA may help predict treatment response in patients with secondary RP.

Oral arsenic trioxide-based regimen as salvage treatment for relapsed or refractory mantle cell lymphoma.

BACKGROUND: Mantle cell lymphoma (MCL) is aggressive, and relapsed/refractory disease has poor outcomes. PATIENTS AND METHODS: Thirty-nine patients (men = 34, women = 5) at 64 (41-82) years of age with relapsed/refractory MCL, ineligible for high-dose chemotherapy and had received 2 (1-5) prior regimens, were treated with a continuous oral regimen, comprising oral arsenic trioxide (oral-As2O3), chlorambucil and ascorbic acid. RESULTS: Overall response rate was 49% (complete response, CR = 28%; partial response, PR = 21%). Only grade 1/2 toxicities were observed (hematologic: 56%, hepatic: 8%). Response was maintained in 11 patients (CR = 8; PR = 3), after a median of 24 (2-108) months. Independent prognostic factors for response were increased lactate dehydrogenase (P = 0.04) and unfavorable MCL international prognostic index (P = 0.04). At a median follow-up of 21 (1-118) months, the median progression-free survival (PFS) was 16 months, and overall survival (OS) 38 months. Independent prognostic factors for PFS were female gender (P = 0.002), and Eastern Cooperative Oncology Group (ECOG) performance score of 2 (P = 0.009). Independent prognostic factors for OS were female gender (P < 0.001), ECOG performance score of 2 (P = 0.03), non-response (P < 0.001), and disease progression after initial response (P = 0.05). CONCLUSION: An oral regimen of oral-As2O3, chlorambucil and ascorbic acid was active with minimal toxicity in relapsed/refractory MCL, achieving durable responses in ∼30% of cases.