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.

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.

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.

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.

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.

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.

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.

Usefulness of ST elevation II/III ratio and ST deviation in lead I for identifying the culprit artery in inferior wall acute myocardial infarction.

In a study of 92 patients presenting with inferior wall acute myocardial infarction, the infarct-related artery was the right coronary artery in 72 patients (78%) and the left circumflex artery in 20 (22%). An ST II/III ratio of 1 or an isoelectric ST in lead I are sensitive and specific markers of left circumflex artery occlusion, whereas an ST II/III ratio <1 (ST elevation in lead III >II) or ST depression in lead I are sensitive and specific markers of right coronary artery occlusion.

Interleukin-6 in experimental endometriosis.

OBJECTIVE: To measure the concentration of interleukin-6 (IL-6) in peripheral serum and conditioned media (CM) of macrophages collected from the peritoneal cavity in rats before and after surgically inducing endometriosis. DESIGN: Adult female rats (n = 50) underwent autotransplantation of adipose tissue or uterine squares. Peritoneal cavity macrophages were collected at the initial laparotomy. Rats were killed 4 or 8 weeks later, and peripheral serum and peritoneal cavity macrophages were collected. Macrophages were cultured for 48 hours, and the IL-6 concentrations in CM and serum were measured using the B9 hybridoma cell line bioassay. RESULTS: Serum IL-6 levels were significantly increased at 4 weeks but not at 8 weeks in rats receiving endometrial implants. Interleukin-6 production by macrophages from rats with endometrial implants at 4 or 8 weeks was not significantly different from baseline or from rats receiving adipose tissue implants. CONCLUSION: The increased serum IL-6 levels at 4 but not 8 weeks after surgical induction of endometriosis suggest that IL-6 may be involved in the initial development of endometriosis in this experimental model.

Muscle activation during the tennis volley.

PURPOSE: To broaden our understanding of muscle function during the tennis volley under different ball placement and speed conditions by examining the activity of selected superficial muscles of the stroking arm and shoulder (flexor carpi radialis, extensor carpi radialis, triceps brachii, deltoids, and pectoralis major) and muscles related to postural support (left and right external oblique, lumbar erector spinae, and gastrocnemius) during the volley. METHODS: Seven skilled tennis players were asked to perform volley strokes under 18 experimental conditions, including variations in lateral contact location (forehand and backhand), ball contact height (high, middle, and low), and ball speed (fast, medium, and slow). A ball machine was modified so that the subjects could not predict the ball trajectory before it was released from the machine. Muscle activity was determined using surface electromyographic (EMG) techniques, and the critical instants of a volley were determined using two force platforms and two high-speed (120 Hz) video cameras. Average EMG values for different phases of the volley, defined by the critical instants, were computed. RESULTS AND CONCLUSIONS: In general, muscle activity increased with increasing ball speed. The extensor carpi radialis was more active than the flexor carpi radialis during both forehand and backhand volleys, suggesting the importance of wrist extension/abduction and grip strength. The increase in EMG levels in the forearm muscles shortly before the ball impact indicated that the subjects did not tighten their grip and wrist until moments before ball impact. Both antero-middle and postero-middle deltoids were active in most stroke phases. However, the roles of the deltoid muscles during a volley cannot be determined without knowing the actions of the other shoulder joint muscles.

Movement characteristics of the tennis volley.

PURPOSE: The purpose of this study was to examine selected movement characteristics of the tennis volley by evaluating temporal and ground reaction force (GRF) parameters. METHODS: Seven skilled tennis players performed volley strokes under 18 experimental conditions including variations in lateral contact location (forehand (FH) and backhand (BH)), ball contact height (high, middle, low), and ball speed (fast, medium, slow). A ball machine was modified so that the subjects could not predict the ball trajectory before it was released from the machine. The GRF and temporal parameters were determined using two force platforms and two high-speed (120 Hz) video cameras, respectively. Average and maximum values of each measured parameter were computed for different phases of the volley. RESULTS: The average reaction times (from ball release to initial racquet movement (IRM)) for FH and BH trials were 226 and 205 ms, respectively, and the difference was statistically significant. The average stroke time (from IRM to ball impact) ranged from 381 ms in fast speed trials to 803 ms in slow speed trials. A distinct racquet forward motion immediately before ball impact occurred in 75% of the trials and they were evenly distributed between FH and BH trials. An ipsilateral side step (a side step of the foot on the same side of the oncoming ball before the crossover step of the other foot) occurred more often in FH (45%) than in BH (34%) trials. CONCLUSIONS: The GRF during the stroke phase suggest that the subjects initiated lateral movement by leaning sideward when ball velocity was low and by a vigorous pushoff of the contralateral foot when ball velocity was high.

Right sided chest lead electrocardiographic abnormalities in acute pulmonary embolism.

Twelve lead electrocardiograms together with right-sided chest leads V4R, V5R and V6R were recorded in four patients with acute pulmonary embolism. All four patients showed ST segment elevation and a qs or qr pattern (with prominent q waves) in one to three of the leads V4R, V5R and V6R. These abnormalities were absent in the repeat electrocardiograms which were recorded after the acute illness.

Left bundle branch block and increased transverse:frontal plane QRS voltage ratio in severe left ventricular dysfunction.

Six patients with complete left bundle branch block and an increase in the transverse:frontal plane QRS voltage ratio are described. All these patients presented with congestive heart failure which was due to severe left ventricular dysfunction.

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.

Value of troponin-T rapid assay, cardiac enzymes, electrocardiogram and history of chest pain in the initial diagnosis of myocardial infarction in the emergency department.

We conducted a prospective study of 152 adult patients presenting to an emergency department with chest pain or symptoms suggestive of acute myocardial infarction (AMI) to evaluate the first electrocardiogram (ECG), creatine kinase (CK)-MB and Troponin-T Rapid Assay (TnT) alone or in combination with chest pain in the initial diagnosis of AMI. A provisional diagnosis was made after the history, physical examination and the first ECG reading. Blood specimens were taken for TnT, CK and CK-MB mass. A final discharge diagnosis of AMI was made according to World Health Organization criteria. Seventy-six (50%) of patients had a final diagnosis of AMI. The sensitivities of the first ECG, first CK-MB mass and first TnT were 76.3% (95% confidence interval (CI), 66.8-85.9), 38.2% (95% CI, 27.2-49.1) and 31.6% (95% CI, 21.2-42.0) respectively. The area under the curve for a combination of ECG, CK-MB mass, TnT and chest pain was the highest at 0.937 when compared with chest pain with varying combinations of tests. A combination of the first ECG, CK-MB mass and TnT had a negative predictive value (NPV) of 87.9% (95% CI, 80.0-95.8). The first ECG was the most sensitive test while the combination of chest pain, ECG, cardiac enzymes and TnT gave the best results in the initial diagnosis of AMI. If the first ECG, CK-MB mass and TnT are all negative, the probability of having an AMI is 12%.

Analysis methods to improve the diagnostic power of treadmill exercise stress testing in patients with suspected angina pectoris.

To assess the ability of 3 established analysis methods in exercise stress electrocardiography to non-invasively detect the presence of coronary artery disease (CAD), 67 consecutive patients who had typical angina, positive exercise stress electrocardiography (ST segment depression > or = 1 mm) and coronary arteriography were studied. Thirty-three patients had significant CAD, and 34 had normal coronary arteriograms. The results showed that the Treadmill Score Method, utilising both ST and non-ST segment variables, had the highest accuracy in predicting disease. The predictive power of all 3 methods was lower in females.

Severe aortic regurgitation due to Neisseria mucosa endocarditis.

A rare occurrence of Neisseria mucosa endocarditis on a native aortic valve not known to be diseased is reported. Despite vigorous antibiotic therapy, severe aortic regurgitation developed necessitating aortic valve replacement. At operation, the right coronary cusp was retracted with two small nodules attached to its edge and the non-coronary cusp was perforated. Neisseria mucosa endocarditis is very rare, and involves abnormal mitral or prosthetic valves predominantly. Infection of a native aortic valve, with no known history of disease, is exceptional.