Mepolizumab in children and adolescents with severe eosinophilic asthma not eligible for omalizumab: a single Center experience.

BACKGROUND: Mepolizumab is an anti-interleukin-5 monoclonal antibody shown to reduce asthma exacerbations in adults and adolescents with severe eosinophilic asthma. AIM: To assess the impact of mepolizumab on children and adolescents over 12 months by examining steroid usage, asthma-related hospitalizations, Asthma Control Test (ACT) scores, fractional exhaled nitric oxide concentration (FeNO), forced expiratory volume in 1 s (FEV1), mid expiratory flow (FEF25-75%), and blood eosinophil count. METHODS: Retrospective analysis performed between October 2015 and December 2022. Data was reviewed 12 months before and after commencing mepolizumab. Mepolizumab was offered if the patient had severe eosinophilic asthma and were unresponsive to or ineligible for omalizumab. RESULTS: Sixteen participants (age 7-17, 8 males, 8 females) received subcutaneous mepolizumab monthly with no serious adverse reactions. Incidence of hospital admissions fell significantly (IRR 0.33, p = 0.007). Among the 11 patients receiving daily oral corticosteroids, 3 were weaned off daily oral steroids and 3 patients' daily dose was significantly reduced (mean Δ-0.095 ± 0.071 mg/kg, p = 0.0012). Eosinophil count was decreased (mean Δ-0.85 x 109/L, p < 0.001). There was no significant change in mean overall steroid burden per patient (mean Δ-1445.63 ± 1603.18 mg, p = 0.10), ACT scores (mean Δ2.88 ± 6.71, p = 0.17), FEV1 z-scores (mean Δ-0.99 ± 1.88, p = 0.053), FEF25-75% z-scores (mean Δ-0.65 ± 1.61, p = 0.13), FeNO (mean Δ-20.09 ± 80.86, p = 0.34), or number of courses of oral steroids given for asthma attacks (IRR 0.71, p = 0.09). CONCLUSION: Among children and adolescents with severe eosinophilic asthma ineligible for or not responsive to omalizumab, mepolizumab therapy exhibited significant reduction in rate of asthma-related hospitalizations and significant decrease in daily steroid dosage.

Liver disease among patients with psoriasis: the Malaysian Psoriasis Registry.

BACKGROUND: Therapeutic options may be limited for patients with psoriasis who have concomitant liver disease (PsL). OBJECTIVES: We aimed to report the frequency of liver disease among patients with psoriasis, and describe the clinical features, treatment modalities and quality of life. METHODS: This was a multicentre cross-sectional study of patients with psoriasis notified to the Malaysian Psoriasis Registry (MPR) from January 2007 to December 2018. RESULTS: Of 21 735 patients with psoriasis, 174 (0.8%) had liver disease. The three most common liver diseases were viral hepatitis (62.1%), fatty liver (14.4%) and liver cirrhosis (10.9%). The male-to-female ratio was 3.8 : 1. Mean age (SD) of onset of psoriasis was higher in those with liver disease vs. those without [37.25 years (13.47) vs. 33.26 years (16.96), P < 0.001]. Patients with PsL, compared with those without liver disease, had a higher rate of dyslipidaemia (27.5% vs. 16.4%, P < 0.001), hypertension (33.9% vs. 23.7%, P = 0.002), diabetes mellitus (22.4% vs. 15.9%, P = 0.021) and HIV infection (5.3% vs. 0.4%, P < 0.001). Those with PsL were also more likely than those without liver disease to have severe disease [body surface area > 10% and/or Dermatology Life Quality Index (DLQI) > 10] (59.3% vs. 49.9%, P = 0.027), psoriatic arthropathy (21.1% vs. 13.0%, P = 0.002) and nail involvement (78.2% vs. 56.1%, P < 0.001). Also significantly higher in the group with PsL were the use of phototherapy (8.4% vs. 2.6%, P < 0.001), acitretin (7.3% vs. 2.8%, P < 0.001) and ciclosporin (3.0% vs. 0.7%, P < 0.001). Mean DLQI was similar in both groups [9.69 (7.20) vs. 9.62 (6.75), P = 0.88]. CONCLUSIONS: The frequency of patients with PsL in the MPR was 0.8%. Patients with PsL were more likely to be male, had a higher rate of comorbidities, severe disease, and nail and joint involvement than those without liver disease.

Facilitators and Barriers to Post-partum Diabetes Screening Among Mothers With a History of Gestational Diabetes Mellitus-A Qualitative Study From Singapore.

Introduction: Gestational Diabetes Mellitus (GDM) affects one in six births worldwide. Mothers with GDM have an increased risk of developing post-partum Type-2 Diabetes Mellitus (T2DM). However, their uptake of post-partum diabetes screening is suboptimal, including those in Singapore. Literature reports that the patient-doctor relationship, mothers' concerns about diabetes, and family-related practicalities are key factors influencing the uptake of such screening. However, we postulate additional factors related to local society, healthcare system, and policies in influencing post-partum diabetes screening among mothers with GDM. Aim: The qualitative research study aimed to explore the facilitators and barriers to post-partum diabetes screening among mothers with GDM in an Asian community. Methods: In-depth interviews were carried out on mothers with GDM at a public primary care clinic in Singapore. Mothers were recruited from those who brought their child for vaccination appointments and their informed consent was obtained. Both mothers who completed post-partum diabetes screening within 12 weeks after childbirth and those who did not were purposively recruited. The social ecological model (SEM) provides the theoretical framework to identify facilitators and barriers at the individual, interpersonal, organizational, and policy levels. Results: Twenty multi-ethnic Asian mothers with GDM were interviewed. At the individual and interpersonal level, self-perceived risk of developing T2DM, understanding the need for screening and the benefits of early diagnosis, availability of confinement nanny in Chinese family, alternate caregivers, emotional, and peer support facilitated post-partum diabetes screening. Barriers included fear of the diagnosis and its consequences, preference for personal attention and care to child, failure to find trusted caregiver, competing priorities, and unpleasant experiences with the oral glucose tolerance test. At the organizational and public policy level, bundling of scheduled appointments, and standardization of procedure eased screening but uptake was hindered by inconvenient testing locations, variable post-partum care practices and advice in the recommendations for diabetes screening. Conclusion: Based on the SEM, facilitators and barriers towards post-partum diabetes screening exist at multiple levels, with some contextualized to local factors. Interventions to improve its uptake should be multi-pronged, targeting not only at personal but also familial, health system, and policy factors to ensure higher level of success.

Role of contrast-enhanced ultrasound in the evaluation of post-liver transplant vasculature.

Liver transplantation is a frequently used treatment for patients with end-stage liver disease and ultrasound is often the first-line imaging technique for detection of vascular complications after liver transplant. Although colour Doppler ultrasound is a good screening method for evaluation of post-liver transplant vasculature, it has limitations in evaluating small-calibre vessels and vessels in close proximity. Contrast-enhanced ultrasound (CEUS) has been proposed to overcome these limitations by improving visualisation of post-liver transplant vasculature and reducing the number of false-positive cases, which necessitate unnecessary additional investigations such as computed tomography or angiography. Liver transplant anatomy and the wide array of post-transplant imaging findings on colour Doppler have already been well described but literature on the use of CEUS and its image interpretation remain scarce. This review aims to discuss the indications for CEUS after liver transplant, to demonstrate CEUS technique and familiarise readers with the imaging appearances of post-transplant vascular complications on CEUS.

Prevalence of type 5 familial hemophagocytic lymphohistiocytosis in Korea and novel mutations in STXBP2.

Familial hemophagocytic lymphohistiocytosis (F-HLH or FHL) is a potentially fatal immune dysregulation syndrome with a heterogeneous genetic background. Most recently, STXBP2 has been identified as the causative gene of type 5 FHL (FHL5) with a worldwide distribution. In this study, we investigated the prevalence of FHL5 in Korea. About 50 Korean pediatric patients with HLH who lacked pathogenic mutations in PRF1, UNC13D, or in STX11 from the previous series of 72 patients with HLH were analyzed for STXBP2 mutations by conventional sequencing analyses. As a result, we found one patient with two novel mutations of STXBP2: c.184A>G and c.577A>C. c.184A>G (p.Asn62Asp) was located within a highly conserved region of the STXBP2 protein and predicted to be deleterious. c.577A>C in exon 7 resulted in incomplete splicing mutation with exon 7 skipping concurrent with exon 7-retained transcript with p.Lys193Gln substitution. The frequency of FHL5 was ~1% (1/72) in Korean pediatric patients with HLH. This is the first study on FHL5 in Korea, and the data from a nationwide patient cohort provide another piece of genetic profiles of FHL.

Efficacy and safety of micafungin for the prophylaxis of invasive fungal infection during neutropenia in children and adolescents undergoing allogeneic hematopoietic SCT.

The objective of this study was to evaluate the efficacy and safety of micafungin for the prevention of invasive fungal infection (IFI) during the neutropenic phase of allogeneic hematopoietic SCT (allo-HSCT) in children and adolescents. This was a prospective, multicenter, open-label, single-arm study. Micafungin was administered i.v. at a dose of 1 mg/kg/day (max 50 mg) from the beginning of conditioning until neutrophil engraftment. Treatment success was defined as the absence of proven, probable, possible or suspected IFI through to 4 weeks after therapy. From April 2010 to December 2011, 155 patients were enrolled from 11 institutions in Korea, and 147 patients were analyzed. Of the 147 patients, 121 (82.3%) completed the protocol without premature interruption. Of the 132 patients in whom micafungin efficacy could be evaluated, treatment success was achieved in 119 patients (90.2%). There was no proven fungal infection in any patient. The number of patients with probable, possible and suspected IFI was two, two and nine, respectively. Thirty-five patients (23.8%) experienced 109 adverse events (AEs) possibly related to micafungin. No patients experienced grade IV AEs. Two patients (1.4%) discontinued micafungin administration due to adverse effects. None of the deaths were related to the study drug.

Bisphosphonate use and subsequent hip fracture in South Korea.

UNLABELLED: We determined the incidence of second hip fracture and evaluated whether compliant and persistent users of bisphosphonate had a lower incidence of second hip fracture after prior hip fracture, from a national claim registry. INTRODUCTION: Bisphosphonate is prescribed worldwide for the primary prevention of osteoporotic fracture. However, the association between adherent use of bisphosphonate and prevention of second hip fracture is unclear. Our purpose was to determine whether the adherent use of bisphosphonate was associated with a decreased risk of second hip fracture in South Korea, using a nationwide database. METHODS: From 2007 to 2011, first and second hip fractures were identified using the ICD-10 and procedure code form from the nationwide database of the Health Insurance Review and Assessment Service. Compliant use of bisphosphonate was defined as a patient medication possession ratio of 80 or more. Persistent users were defined patients with a refill gap of 30 days or less. We compared the incidence of second hip fracture in compliant and persistent users and non-users. RESULTS: Among 59,782 patients with first hip fracture, in this study, 1,336 second hip fracture occurred after the initial hip fracture during the study period. The mean age at the first hip fracture was 75.4 years (range, 50 to 100 years). The cumulative 1-year, 2-year, and 3-year incidence of second hip fracture was 1.0% (552/59,782), 1.9% (1,123/59,782), and 2.2% (1,336/59,782), respectively. After multivariate analysis, compliant and persistent use of bisphosphonate was significantly independent protectors for second hip fracture (HR, 0.595; 95% CI, 0.400-0.885; HR, 0.433; 95% CI, 0.327-0.573, respectively). CONCLUSIONS: Compliant and persistent use of bisphosphonate decreases the risk of second hip fracture, in terms of secondary prevention.

Oral administration of Lactobacillus strains from Kimchi inhibits atopic dermatitis in NC / Nga mice.

AIMS: Atopic dermatitis (AD) is marked by elevated levels of immunoglobulin E and skin lesions such as oedema and haemorrhage. Kimchi is a Korean fermented food that contains beneficial bacteria for human health. In this study, Lactobacillus plantarum CJLP55, CJLP56, CJLP133 and CJLP136 isolated from Kimchi were investigated for their capacity to inhibit AD. METHODS AND RESULTS: The three strains, CJLP55, CJLP133 and CJLP136, suppressed AD-like skin lesions, high serum IgE levels and epidermal thickening. The three strains diminished the accumulation of eosinophils and mast cells into topical inflammatory sites and the enlargement of axillary lymph nodes, which are responsible for the dorsal dermatitis. CJLP55, CJLP133 and CJLP136 decreased production of type 2 cytokines such as IL-4 and IL-5 in lymph node cell culture. CJLP133 and CJLP136 increased IFN-γ secretion, while CJLP55 enhanced IL-10 production. CONCLUSIONS: The three strains isolated from Kimchi suppress house-dust mite-induced dermatitis in NC/Nga mouse, a representative animal model of human AD. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings suggest that lactobacilli isolated from Kimchi inhibit AD, probably by altering the balance of Th1/Th2 ratio or inducing IL-10 production.

Assessment of colorectal cancer knowledge and patient attitudes towards screening: is Ireland ready to embrace colon cancer screening?

INTRODUCTION: The level of awareness among the Irish public regarding colorectal cancer (CRC) remains uncertain. This study aimed to characterise CRC knowledge levels among a cohort of Irish patients. METHODS: A survey evaluating CRC knowledge levels was distributed among outpatients at a gastroenterology clinic in a Dublin teaching hospital. RESULTS: In total, 472 surveys were distributed of which 465 (98.5%) were returned. Twenty-nine percent of respondents correctly judged CRC to be the commonest cause of cancer death among the options provided while 26% correctly judged the lifetime risk of CRC; 59% underestimated and 15% overestimated the risk. Most patients (91%) were willing to pay 300 euros for a prompt colonoscopy if recommended by their physician while 7% opted to wait 6 months for a free colonoscopy. CONCLUSIONS: There is a willingness to embrace CRC screening and to shoulder some of the financial burden that this entails.

Simultaneous thromboses of multiple coronary arteries in acute myocardial infarction.

Simultaneous thrombotic occlusion of multiple coronary arteries in acute myocardial infarction is a well-recognised phenomenon. Studies have reported diffuse destabilisation of atherosclerotic plaques in patients with acute myocardial infarction, leading to the concept of "pan-coronaritis". The putative mechanism is attributed to a systemic thrombophilic and inflammatory state. We report the occurrence of this phenomenon in two middle-aged male patients.

Clinical predictors of a positive troponin T test in patients presenting with probable acute coronary syndromes.

Acute coronary syndrome (ACS) patients with positive troponin T (TnT) test are at higher risk for death and myocardial reinfarction. They would significantly benefit from early aggressive pharmacologic and invasive therapy. However, TnT test is not widely available. This retrospective study of 173 patients with ACS showed: that prolonged or repetitive episodes of angina at rest in the previous 24 hours (p = 0.01) and evidence of myocardial ischaemia on ECG (p < 0.001) were associated with positive TnT tests (> or = 0.1 ng/mL). The two variables in combination showed 100% positive predictive value, facilitating early identification and streamlining of therapy.

ReoPro Observational Registry (RAPOR): insights from the multicentre use of abciximab in Asia.

INTRODUCTION: The pattern of use of abciximab in real-life clinical patients undergoing percutaneous coronary intervention (PCI) in 11 high-volume centres in Singapore, Malaysia, Thailand, Philippines, India, Pakistan and Korea was prospectively examined. METHODS: These centres enrolled 224 consecutive patients over eight months to receive abciximab during PCI for the study. The cohort consisted of 82.1 percent males, with mean age of 55 (+/- 11) years and mean weight of 67 (+/- 17) kg. RESULTS: The use of abciximab during PCI ranged between 6.2 percent and 21.6 percent. The indications for the use of abciximab were: acute coronary syndromes (34.3 percent), complex coronary lesions (17.9 percent) and multivessel PCI (17.7 percent). Based on a risk scoring system devised for this registry, majority (60.0 percent) of the patients was considered high risk when abciximab was used. Among the patients enrolled, 36.6 percent received abciximab as a "bail-out". The overall in-hospital ischaemic event rates were low at 4.0 percent. The complication rates included major bleeding 0.7 percent, thrombocytopenia 2.7 percent and need for blood transfusion 2.8 percent. There was a trend towards a higher incidence of in-hospital non-Q myocardial infarction in the "bail-out" group (2.1 percent versus 7.3 percent, p-value equals 0.07). CONCLUSION: Abxicimab was uncommonly used among patients (9.4 percent) undergoing PCI in this Asian region, with the operators reserving it mainly for high-risk patients.

Human VEGF165-myoblasts produce concomitant angiogenesis/myogenesis in the regenerative heart.

Bioengineering the regenerative heart may provide a novel treatment for heart failure. On May 14, 2002, a 55-year-old man suffering from ischemic myocardial infarction received 25 injections carrying 465 million cGMP-produced pure myoblasts into his myocardium after coronary artery bypass grafting. As on August 28, 2002, his EKG was normal and showed no arrhythmia. His ejection fraction increased by 13%. He no longer experienced shortness of breath and angina as he did before the treatment. Three myogenesis mechanisms were elucidated with 17 human/porcine xenografts using cyclosporine as immunosuppressant. Some myoblasts developed to become cardiomyocytes. Others transferred their nuclei into host cardiomyocytes through natural cell fusion. As yet others formed skeletal myofibers with satellite cells. De novo production of contractile filaments augmented the heart contractility. Human myoblasts transduced with VEGF165 gene produced six times more capillaries in porcine myocardium than in placebo. Xenograft rejection was not observed for up to 20 weeks despite cyclosporine discontinuation at 6 weeks. Pros and cons of autografts vs. allografts are compared to guide future development of heart cell therapy.

High-sensitivity C-reactive protein is predictive of medium-term cardiac outcome in high-risk Asian patients presenting with chest pain syndrome without myocardial infarction.

INTRODUCTION: High-sensitivity C-reactive protein (hs-CRP) has been shown to be predictive of cardiac events but data among Asians is comparatively few. We evaluated the role of hs-CRP in the prediction of adverse cardiac outcome in a cohort of high-risk patients presenting with chest pain syndrome without myocardial infarction (MI). MATERIALS AND METHODS: Three hundred and forty-seven patients were prospectively recruited over an 18-month period and patients with MI as documented by serial electrocardiogram abnormalities, and creatinine kinase or troponin elevation were excluded. Mean follow-up duration was 901 +/- 306 days. Kaplan-Meier and Cox proportional hazards modelling were used to evaluate outcome and determine association with predictor variables. RESULTS: The composite primary endpoint of cardiac mortality, non-fatal MI, cardiac failure or coronary revascularisation procedure (coronary artery bypass grafting or angioplasty) unrelated to the index admission was reached in 37 patients. History of previous MI (P = 0.002), presence of at least 1 coronary artery with > or =50% stenosis (P = 0.028) and elevated hs-CRP levels were associated with an adverse cardiac outcome (P = 0.001 for CRP in the upper quartile, and 0.002 for CRP > or = 1mg/L, respectively). None of the traditional cardiovascular risk factors (hypertension, diabetes mellitus, dyslipidaemia, significant family history, smoking, male gender and increased age) was predictive. Multivariate modelling showed elevated hs-CRP to confer the highest risk for an adverse cardiac outcome (P <0.001). CONCLUSION: Hs-CRP is useful in further stratifying high-risk multi-ethnic patients presenting with chest pain despite no evidence of MI. Close follow-up and aggressive management of these patients may be warranted.

The impact of diabetes mellitus on the prognostic value of a normal dobutamine stress echocardiogram in patients with intermediate to high cardiovascular risk.

INTRODUCTION: There is currently limited data on the prognostic value of a normal dobutamine stress echocardiogram (DSE) in patients with intermediate to high cardiovascular risk. The impact of diabetes mellitus, recently recognised as a cardiovascular risk-equivalent, has not been previously evaluated. This study aims to determine the prognostic value of a normal DSE in these patients. METHODS: The study population includes all patients with two cardiovascular risk factors or diabetes mellitus and a normal DSE (baseline and peak stress) with three months follow-up. A total of 122 patients (47 females, 75 males; mean age 59.6 years) were recruited. Impact of diabetes mellitus on subsequent cardiovascular events was determined. RESULTS: Diabetes mellitus was present in 32.8 percent, hypertension in 72.1 percent, smoking in 27.0 percent, family history of premature coronary artery disease in 15.6 percent, and hypercholesterolemia in 66.4 percent. On follow-up until 6.4 years (mean 4.1 years), there were four myocardial infarctions (0.8 percent per patient/year) and five revascularisation procedures (1.0 percent per patient/year). The majority of adverse events occurred among patients with diabetes mellitus (three out of four myocardial infarctions; four out of five revascularisations). Diabetes mellitus independently predicted subsequent cardiac events on both univariate and multivariate analyses (p value is equal to 0.015 and 0.011, respectively). Presence of diabetes mellitus also conferred a worse outcome on survival analysis (p value is equivalent to 0.0046). CONCLUSION: The presence of diabetes mellitus adversely affects clinical outcome despite a normal DSE. Patients without diabetes mellitus, but with intermediate to high cardiovascular risk, and a normal DSE have a better medium term outcome.

Human VEGF165-myoblasts produce concomitant angiogenesis/myogenesis in the regenerative heart.

Bioengineering the regenerative heart may provide a novel treatment for heart failure. On May 14, 2002, a 55-year-old man suffering from ischemic myocardial infarction received 25 injections carrying 465 million cGMP-produced pure myoblasts into his myocardium after coronary artery bypass grafting. As on August 28, 2002, his EKG was normal and showed no arrhythmia. His ejection fraction increased by 13%. He no longer experienced shortness of breath and angina as he did before the treatment. Three myogenesis mechanisms were elucidated with 17 human/porcine xenografts using cyclosporine as immunosuppressant. Some myoblasts developed to become cardiomyocytes. Others transferred their nuclei into host cardiomyocytes through natural cell fusion. As yet others formed skeletal myofibers with satellite cells. De novo production of contractile filaments augmented the heart contractility. Human myoblasts transduced with VEGF165 gene produced six times more capillaries in porcine myocardium than in placebo. Xenograft rejection was not observed for up to 20 weeks despite cyclosporine discontinuation at 6 weeks. Pros and cons of autografts vs. allografts are compared to guide future development of heart cell therapy. (Mol Cell Biochem 263: 173-178, 2004).

Lower trunk muscle activity during the tennis serve.

Prior electromyographic (EMG) analyses of the tennis serve have focused on the muscles in the hitting arm and shoulder region. This preliminary study aimed to examine the muscle activation patterns of selected lower trunk muscles during three different types of tennis serve--flat, topspin, and slice. Five male highly skilled tennis players completed 10 trials for each type of serve. Surface EMG electrodes were used to monitor the rectus abdominis (RA), external oblique (EO), internal oblique (IO), and lumbar erector spinae (ES) muscles. For each subject, the two trials with the highest self-reported ratings were analysed. Average EMG levels during each phase of a tennis serve for each muscle were analysed using a non-parametric ANOVA design. No major differences in muscle activation pattern were found across different serve types, and bilateral differences in muscle activation were more pronounced in RA and EO than in IO and ES muscles. The abdominal muscles were more active in the topspin than in the other two types of serves during the upward swing of the racket. An appreciable amount of abdominal/low back and bilateral co-activation was observed during certain phases of the serve. The co-activation of lower trunk muscles may help to stabilise the lumbar spine during the arch back and forward swing phases of the serve. The results reinforce the importance of abdominal and low back exercises in the strength and rehabilitation programs designed for tennis players.