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Factors determining the responsiveness to antithyroid drugs (ATDs) in Graves' disease are not fully known. Notwithstanding the typical pattern and tempo of thyroid hormone responses to thionamides, the existence of an unusual subset of Graves' disease with extraordinarily rapid thyroid hormone responses to ATDs will prove challenging even to the expert clinician. Termed 'rapid responder Graves' disease' or 'high turnover Graves' disease', the serum thyroxine (FT4) and triiodothyronine (FT3) of patients with this variant of thyrotoxicosis can decline precipitously during the initiation of ATDs and yet escalate acutely upon discontinuation of pharmacological intervention. We describe a case that presented with low serum FT4 and FT3 in association with suppressed serum thyrotropin (TSH) concentrations soon after starting carbimazole even at a low dose. The erratic clinical course comprising largely of serum FT4 nadirs and peaks is elaborated to facilitate appreciation of the difficulty in the stabilization of the thyroid with ATDs. The possible pathogenetic mechanisms for the chaotic fluctuations in thyroid hormones to minor changes in thionamide dose adjustments are discussed as well. [ABSTRACT FROM AUTHOR]

Introduction: A resurgence of pertussis has been reported in numerous countries. This study aimed to determine the incidence, clinical characteristics, and outcome of pertussis among infants in Sarawak, Malaysia., Methodology: We conducted a descriptive retrospective study of infants aged < 12 months with laboratory-confirmed pertussis admitted to Bintulu Hospital in Sarawak, Malaysian Borneo, from 2015 until 2021. Pertussis was confirmed in all patients using a polymerase chain reaction of nasopharyngeal aspirates., Results: Of 588 infants who had a nasopharyngeal aspirate, 108 (18%) had laboratory-confirmed pertussis. The average annual incidence was 482 per 100,000 infants aged < 12 months between 2015 and 2019, with a marked decline in 2020 and 2021. Eighty-two (76%) were < 3 months of age. Seventy-eight (72%) were unvaccinated for pertussis, including 75 (96%) who were too young to receive the first dose. A third of the cases had atypical presentations. Severe disease characterized by hypoxemia, pulmonary hypertension, recurrent apnea, encephalopathy, or cardiovascular dysfunction occurred in 32%. Forty-eight percent required humidified high-flow nasal cannula oxygen therapy and 22% required invasive ventilation. Twenty-four percent overall needed intensive care. One (1%) infant had a fatal outcome. Nearly all cases of severe disease or those that required invasive ventilation or intensive care had received ≤ 1 dose of pertussis vaccination., Conclusions: A high incidence of pertussis with a high rate of severe disease was observed in Sarawak, Malaysia, predominantly among infants too young to be vaccinated. Additional vaccination strategies such as maternal vaccination or cocooning should be considered., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Anand Mohan, Yee-Yen Tan, Rohaidah Hashim, David Chun-Ern Ng, Veronica Huey-Shin Wong, Da-Wei Liew, Su-Lin Chien, Lee-See Tan, Peter Sie-Teck Lau, Thilagam Rajandran, Yuwana Podin, Mong-How Ooi.)

The BCG vaccine is considered a safe and efficacious vaccine in the prevention of severe forms of tuberculosis. BCG osteomyelitis is a rare complication of the BCG vaccine that occurs in vaccinated young children. We report a case of BCG osteomyelitis in a male toddler, presenting with painful left wrist swelling without preceding fever or systemic symptoms. Radiographic evidence of osteomyelitis in the left wrist was observed. Initial treatment with conventional antibiotics for acute haematogenous osteomyelitis showed no improvement. The diagnosis of Mycobacterium bovis BCG osteomyelitis was confirmed via tissue samples for histopathological examination and mycobacterial cultures. The patient responded well to treatment with oral antituberculous therapy. This case highlights the importance of considering BCG osteomyelitis in the differential diagnosis of unexplained joint swelling in BCG-vaccinated young children., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Mitophagy must be carefully regulated to ensure that cells maintain appropriate numbers of functional mitochondria. The SCF FBXL4 ubiquitin ligase complex suppresses mitophagy by controlling the degradation of BNIP3 and NIX mitophagy receptors, and FBXL4 mutations result in mitochondrial disease as a consequence of elevated mitophagy. Here, we reveal that the mitochondrial phosphatase PPTC7 is an essential cofactor for SCF FBXL4 -mediated destruction of BNIP3 and NIX, suppressing both steady-state and induced mitophagy. Disruption of the phosphatase activity of PPTC7 does not influence BNIP3 and NIX turnover. Rather, a pool of PPTC7 on the mitochondrial outer membrane acts as an adaptor linking BNIP3 and NIX to FBXL4, facilitating the turnover of these mitophagy receptors. PPTC7 accumulates on the outer mitochondrial membrane in response to mitophagy induction or the absence of FBXL4, suggesting a homoeostatic feedback mechanism that attenuates high levels of mitophagy. We mapped critical residues required for PPTC7-BNIP3/NIX and PPTC7-FBXL4 interactions and their disruption interferes with both BNIP3/NIX degradation and mitophagy suppression. Collectively, these findings delineate a complex regulatory mechanism that restricts BNIP3/NIX-induced mitophagy., (© 2024. The Author(s).)

Introduction: Human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are significant contributors to the burden of acute respiratory infections in children, but data on hMPV from Southeast Asia are limited despite its potential for serious disease. This study aimed to compare the clinical presentation, resource utilisation and outcomes between hMPV and RSV infections in hospitalised Malaysian children., Methods: This retrospective, observational study included children aged ≤12 years old hospitalised with hMPV or RSV, confirmed via direct fluorescent antibody (DFA) methods, between 1 July to 30 October 2022 at Hospital Tuanku Ja'afar Seremban, Malaysia. Demographic, clinical presentation, resource utilisation and outcome data were analysed. Propensity score matching was used to balance cohorts based on key demographic and clinical characteristics., Results: This study included 192 patients, comprising 112 with hMPV and 80 with RSV. hMPV patients were older (median age 20.5 vs. 9.4 months, p < 0.001) and had a higher incidence of comorbidities (24.1% vs. 7.5%, p = 0.003). Fever was more common in the hMPV group (97.3% vs. 73.8%, p < 0.001), but the other clinical manifestations were similar. Postmatching analysis showed higher corticosteroid use in the hMPV group (p = 0.01). No significant differences were observed in the use of other resources, PICU admissions, duration of hospitalisation or mortality rates between both groups., Conclusion: hMPV and RSV infections in children share similar clinical manifestations and outcomes, with hMPV affecting older children and showing higher corticosteroid usage. These findings emphasise the need for equal clinical vigilance for both hMPV and RSV in paediatric respiratory infections., (© 2024 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Competing Interests: Competing interests: None declared.

Background: We aimed to compare the clinical features and severity of the Omicron and Delta variant infections among children hospitalized for coronavirus disease 2019 (COVID-19)., Methods: Children 12 years old or less hospitalized for COVID-19 across five hospitals between January 1, 2021 and March 31, 2022 were identified using the state's pediatric COVID-19 registry. Delta and Omicron-infected patients without previous COVID-19 infection, COVID-19 vaccination, or co-infections were propensity-score matched 1:1 to control for differences in baseline characteristics. Clinical manifestations, treatments, and outcomes were analyzed. Disease severity was assessed using an adapted WHO ordinal scale., Results: Of the initial 1367 patients, 668 had Delta infection and 699 had Omicron infection. Propensity-score matching produced 558 matched pairs. Patients with Omicron infection were more likely to present with croup (the odds ratio, OR, was 10.87, with a 95% confidence interval, CI, ranging from 2.54 to 46.59), lower respiratory tract infection (OR 2.32, 95% CI, 1.48-3.64) and seizures (OR 8.39, 95% CI, 5.04-13.99) compared with those with Delta infection. Omicron was associated with increased odds of moderate/severe disease (OR 6.14, 95% CI, 4.72-7.99) and a greater need for intravenous fluid therapy (OR 6.00, 95% CI, 4.29-8.39), corticosteroids (OR 3.08, 95% CI, 1.66-5.72), empirical antibiotics (OR 1.70, 95% CI, 1.10-2.64), and low-flow nasal oxygen therapy (OR 3.68, 95% CI, 2.17-6.22) in comparison with Delta., Conclusion: Children hospitalized with Omicron infection demonstrated a distinct clinical profile compared to those with Delta infection, with increased likelihood of moderate/severe disease and higher utilization of health-care resources., (© 2024 Japan Pediatric Society.)

Competing Interests: Competing interests: None declared.

Introduction: Despite advances in diagnosis and management, patients with advanced pheochromocytomas and paragangliomas (PPGL) face limited treatment options. This study aims to evaluate the safety and efficacy of peptide receptor radionuclide therapy (PRRT) in patients with advanced PPGL, based on a single-institution experience and provide a comprehensive review of the literature., Methods: A retrospective analysis was conducted on patients with advanced pheochromocytoma and paraganglioma who received PRRT at a single institution from April 2012 to March 2022. Clinical characteristics, treatment response, adverse events, and survival outcomes were assessed. A systematic literature review was also performed., Results: A total of 15 patients with advanced PPGL were included, the majority of whom had both metastatic and functional disease. Most patients received four infusions of 177Lu-DOTATATE (73%). The median therapeutic 177Lu-DOTATATE radioactivity for each infusion was 7.4 GBq. Only one patient was treated with one infusion of 90Y-DOTATATE (4.2 GBq) in addition to three infusions of Lu-177 DOTATATE. Overall, PRRT suggests a promising efficacy with disease control rate of 63.6% by RECIST v1.1. The median overall survival (OS) was not reached and the median progression free survival (PFS) was 25.9 months. In terms of safety, PRRT was well tolerated. Review of the literature revealed consistent findings, supporting the efficacy and safety of PRRT in PPGL., Conclusion: This study suggests that PRRT is a safe and effective therapeutic option for patients with PPGL. Our findings align with the existing literature, providing additional evidence to support the use of PRRT in this challenging patient population., (© 2023 British Society for Neuroendocrinology.)

Background: Children account for a significant proportion of COVID-19 hospitalizations, but data on the predictors of disease severity in children are limited. We aimed to identify risk factors associated with moderate/severe COVID-19 and develop a nomogram for predicting children with moderate/severe COVID-19., Methods: We identified children ≤ 12 years old hospitalized for COVID-19 across five hospitals in Negeri Sembilan, Malaysia, from 1 January 2021 to 31 December 2021 from the state's pediatric COVID-19 case registration system. The primary outcome was the development of moderate/severe COVID-19 during hospitalization. Multivariate logistic regression was performed to identify independent risk factors for moderate/severe COVID-19. A nomogram was constructed to predict moderate/severe disease. The model performance was evaluated using the area under the curve (AUC), sensitivity, specificity, and accuracy., Results: A total of 1,717 patients were included. After excluding the asymptomatic cases, 1,234 patients (1,023 mild cases and 211 moderate/severe cases) were used to develop the prediction model. Nine independent risk factors were identified, including the presence of at least one comorbidity, shortness of breath, vomiting, diarrhea, rash, seizures, temperature on arrival, chest recessions, and abnormal breath sounds. The nomogram's sensitivity, specificity, accuracy, and AUC for predicting moderate/severe COVID-19 were 58·1%, 80·5%, 76·8%, and 0·86 (95% CI, 0·79 - 0·92) respectively., Conclusion: Our nomogram, which incorporated readily available clinical parameters, would be useful to facilitate individualized clinical decisions., (© 2023. The Author(s).)

Background: This study aimed to describe the clinical characteristics and severity of young infants hospitalized with COVID-19 and study the relationship between breastfeeding and maternal COVID-19 vaccination on the severity of COVID-19., Methods: A retrospective, observational study was performed among infants aged 6 months and below hospitalized for COVID-19 in a tertiary state hospital in Malaysia between February 1 and April 30, 2022. The primary outcome was "serious disease," defined as pneumonia requiring respiratory support or dehydration with warning signs. Multivariate logistic regression was used to determine independent predictors for serious disease., Results: A total of 102 infants were included in the study; 53.9% were males with a median age of 11 weeks (interquartile range: 5-20 weeks). Sixteen patients (15.7%) had pre-existing comorbidities, including preterm birth. Fever was the most common presenting symptom (82.4%), followed by cough (53.9%), and rhinorrhea (31.4%). Forty-one infants (40.2%) presented with serious disease, warranting either respiratory support or intravenous fluid therapy for dehydration. Recent maternal COVID-19 vaccination was associated with a reduced risk of serious disease on univariate analysis but was not significant after multivariate adjustment (adjusted odds ratio [aOR] 0.39; 95% CI: 0.14-1.11; p = 0.08). Exclusive breastfeeding was protective against serious COVID-19 in young infants, independent of other confounding factors (aOR 0.21, 95% CI: 0.06-0.71; p = 0.01)., Conclusion: COVID-19 is a serious disease with non-specific clinical manifestations in young infants. Exclusive breastfeeding could play an important protective role., (© 2023 Japan Pediatric Society.)

Background: Hepatocellular carcinoma (HCC) is subject to different management approaches and guidelines according to Eastern and Western therapeutic algorithms. Use of selective internal radiation therapy (SIRT) with resin yttrium 90 microspheres for HCC has increased in Asia in recent years, without clearly defined indications for its optimal application. The objective of this systematic review and expert consensus statement is to provide guidance and perspectives on the use of SIRT among patients with HCC in Asia., Materials and Methods: A systematic literature review identified current publications on HCC management and SIRT recommendations. A group of 10 experts, representing stakeholder specialties and countries, convened between August 2020 and March 2021 and implemented a modified Delphi consensus approach to develop guidelines and indications for use of SIRT for HCC in Asia. Final recommendations were organized and adjudicated based on the level of evidence and strength of recommendation, per approaches outlined by the American College of Cardiology/American Heart Association and Oxford Centre for Evidence-Based Medicine., Results: The experts acknowledged a general lack of evidence relating to use of SIRT in Asia and identified as an unmet need the lack of phase 3 randomized trials comparing clinical outcomes and survival following SIRT versus other therapies for HCC. Through an iterative process, the expert group explored areas of clinical relevance and generated 31 guidance statements and a patient management algorithm that achieved consensus., Conclusion: These recommendations aim to support clinicians in their decision-making and to help them identify and treat patients with HCC using SIRT in Asia. The recommendations also highlight areas in which further clinical trials are needed to define the role of SIRT in management of HCC among Asian populations., (Copyright © 2021 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Purpose: This study was performed to evaluate the outcome of implementation of transanal total mesorectal excision (TaTME) for low rectal cancer in a regional hospital and in comparison to laparoscopic (Lap) TME., Methods: Consecutive patients with low rectal cancer of which the lowest border of the tumour was located beween 1 and 5 cm from the puborectalis who underwent TME at North District Hospital between January 2013 and December 2019 were included. Clinical, operative, and pathologic outcomes were compared between Lap TME and TaTME. The primary end point was complication profile., Results: Thirty-five patients underwent Lap TME and 45 patients underwent TaTME for low rectal cancer. The conversion rate of the TaTME group was significantly lower than that of the Lap TME group (4.4% vs. 20%, P=0.029), but the operating time was longer (259 minutes vs. 219 minutes, P=0.009). The tumour location was significantly lower in the TaTME group, but the distal resection margins were adequate and not different between both groups. The TaTME group had higher incidence rates of prolonged ileus and urinary tract infection, but the other complications were similar between the two groups. The resection margin positivity rates of the TaTME and Lap TME groups were 2.2% and 5.7%, respectively (P=0.670). At a median follow up of 39 months, no abnormal early recurrence was detected., Conclusion: It is technically feasible and oncologically safe to perform TaTME in a medium-volume colorectal unit. Patients with difficult pelvic anatomy can benefit by reducing the risk of conversion and margin positivity rate.

Aim: Households are a significant venue for the transmission of SARS-CoV-2. We conducted a study to characterise the transmission dynamics and identify risk factors for household transmission of SARS-CoV-2 in Negeri Sembilan, Malaysia., Methods: This retrospective observational study included 185 families of paediatric COVID-19 cases from 1 February 2020 to 31 December 2020. We identified the index case for each household and gathered the socio-demographic, epidemiological investigation results and risk factors for household transmission from medical case records. The secondary attack rate was calculated, and logistic regression analyses were used to identify risk factors associated with secondary household transmission of SARS-CoV-2., Results: Of the 848 household contacts, 466 acquired secondary infections, resulting in a secondary attack rate of 55%. The median age of the secondary cases was 12 years. Female household contacts and household contacts who slept in the same room with the index case were significantly associated with increased risk for COVID-19. Other independent risk factors associated with higher transmission risk in the household included an index case who was symptomatic, a household index case aged greater than 18 years and a male household index case., Conclusions: High rates of household transmission of COVID-19 were found, indicating households were a major setting of transmission of SARS-CoV-2. Our data provide insight into the risk factors for household transmission of SARS-CoV-2 in Malaysia., (© 2021 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Objectives: We described the etiology of severe pneumonia in children during the height of the COVID-19 pandemic in Malaysia and compared the clinical features of severe SARS-CoV-2 to other respiratory viruses., Methods: This retrospective study included all children aged 12 years and below hospitalized with severe pneumonia in Negeri Sembilan, Malaysia, between 1 April 2021 and 31 October 2021. We extracted demographic and clinical data and used logistic regression to examine risk factors associated with severe SARS-CoV-2 or other viral pneumonia., Results: A total of 111 children were included. The median age was 15 months. Human rhinovirus/enterovirus, SARS-CoV-2 and respiratory syncytial virus were the most common etiology of severe pneumonia. Codetection of >1 viral pathogen was present in 14 (12.6%) patients. Children with severe COVID-19 presented early in the course of illness and had lower rates of pediatric intensive care admission. The presence of sick contact with an adult was a predictor for SARS-CoV-2, whereas adventitious breath sounds were predictive of other respiratory viruses., Conclusions: The etiology of severe pneumonia in children evolved with the epidemic curve of COVID-19 and school closures. Children with severe pneumonia due to SARS-CoV-2 experienced a milder clinical course when compared to other respiratory viruses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ng, Tan, TING, Ling, Fadzilah, TAN, Subramaniam, Zailanalhuddin, LIM, Baharuddin, LEE, Mohamad Nor and Khoo.)

Competing Interests: Competing interests: None declared.

We report a pair of siblings who developed multisystem inflammatory syndrome in children (MIS-C) in close temporal proximity after recent exposure to SARS-CoV-2. Both siblings presented with Kawasaki disease-like features and haemodynamic instability, with the onset of symptoms within 6 days of each other. Remarkably, one of the siblings was the elder of a pair of monozygotic twins. The younger monozygotic twin, however, did not develop MIS-C., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Resistance represents a major challenge for antibody-based therapy for COVID-19 1-4 . Here we engineered an immunoglobulin M (IgM) neutralizing antibody (IgM-14) to overcome the resistance encountered by immunoglobulin G (IgG)-based therapeutics. IgM-14 is over 230-fold more potent than its parental IgG-14 in neutralizing SARS-CoV-2. IgM-14 potently neutralizes the resistant virus raised by its corresponding IgG-14, three variants of concern-B.1.1.7 (Alpha, which first emerged in the UK), P.1 (Gamma, which first emerged in Brazil) and B.1.351 (Beta, which first emerged in South Africa)-and 21 other receptor-binding domain mutants, many of which are resistant to the IgG antibodies that have been authorized for emergency use. Although engineering IgG into IgM enhances antibody potency in general, selection of an optimal epitope is critical for identifying the most effective IgM that can overcome resistance. In mice, a single intranasal dose of IgM-14 at 0.044 mg per kg body weight confers prophylactic efficacy and a single dose at 0.4 mg per kg confers therapeutic efficacy against SARS-CoV-2. IgM-14, but not IgG-14, also confers potent therapeutic protection against the P.1 and B.1.351 variants. IgM-14 exhibits desirable pharmacokinetics and safety profiles when administered intranasally in rodents. Our results show that intranasal administration of an engineered IgM can improve efficacy, reduce resistance and simplify the prophylactic and therapeutic treatment of COVID-19., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives: To describe the clinical and epidemiological characteristics of children with coronavirus disease 2019 (COVID-19) in the state of Negeri Sembilan, Malaysia in the setting of mandatory hospital isolation and quarantine for all confirmed cases., Methods: A multi-centre, retrospective observational study was performed among children aged ≤12 years with laboratory-proven COVID-19 between 1 February and 31 December 2020., Results: In total, 261 children (48.7% males, 51.3% females) were included in this study. The median age was 6 years [interquartile range (IQR) 3-10 years]. One hundred and fifty-one children (57.9%) were asymptomatic on presentation. Among the symptomatic cases, fever was the most common presenting symptom. Two hundred and forty-one (92.3%) cases were close contacts of infected household or extended family members. Twenty-one (8.4%) cases had abnormal radiological findings. All cases were discharged alive without requiring supplemental oxygen therapy or any specific treatment during hospitalization. The median duration of hospitalization was 7 days (IQR 6-10 days). One (2.1%) of the uninfected guardians accompanying a child in quarantine tested positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) upon discharge., Conclusions: COVID-19 in children was associated with mild symptoms and a good prognosis. Familial clustering was an important epidemiologic feature in the outbreak in Negeri Sembilan. The risk of transmission of SARS-CoV-2 from children to guardians in hospital isolation was minimal despite close proximity., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

We report a case of COVID-19 in a 29-week preterm infant. This child is the youngest reported case of SARS-CoV-2 infection in Malaysia, and to the best of our knowledge, one of the youngest documented cases of established vertical transmission of SARS-CoV-2 reported in literature. Our report highlights the clinical course, timelines of viral shedding by real-time reverse transcription-PCR and antibody seroconversion in a premature infant infected with SARS-CoV-2. In addition, we discuss the challenges faced in managing a preterm infant infected with SARS-CoV-2 and the knowledge gaps that need to be explored., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Five children in Pos Lenjang, Pahang, Malaysia were PCR-positive for vivax malaria and were admitted to the hospital from 5 to 26 July 2019. One of the patients experienced three episodes of recurrence of vivax malaria. Microsatellite analysis showed that reinfection is unlikely. Drug resistance analysis indicated that Riamet (artemether-lumefantrine) is effective. Cytochrome P450 2D6 (CYP2D6) testing showed that this patient has defective CYP2D6 function. Primaquine failure to clear the Plasmodium vivax hypnozoites may be the cause of recurring infections in this patient. This report highlights the need for the development of liver-stage curative antimalarials that do not require metabolism by the CYP2D6 enzyme., (© The Author(s) 2020. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Liver cancer is one of the top leading causes of mortality worldwide. Conventional imaging using contrast enhanced CT and MRI are currently the mainstay of oncologic imaging of the liver for the diagnosis and management of cancer. In the past two decades, especially since the advent of hybrid imaging in the form of PET/CT and SPECT/CT, molecular imaging has been increasingly utilized for oncologic imaging and the variety of radionuclide probes for imaging liver cancers have been expanding. Beyond the usual workhorse of FDG as an oncologic tracer, there is a growing body of evidence showing that radiolabeled choline tracers, C-11 acetate and other new novel tracers may have increasing roles to play for the imaging of liver tumors. On the therapy front, there have also been advances in recent times in terms of targeted therapies for both primary and secondary liver malignancies, particularly with transarterial radioembolization. The concept of theranostics can be applied to transarterial radioembolization by utilizing a pretreatment planning scan, such as Tc-99m macroaggregated albumin scintigraphy, coupled with post treatment imaging. Radiation dose planning by personalized dosimetric calculations to the liver tumors is also being advocated. This article explores the general trends in the field of nuclear medicine for the imaging and treatment of liver cancer above and beyond routine diagnosis and management., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Context: To prepare for radioactive iodine therapy in post total thyroidectomy patients with well-differentiated thyroid cancer (WDTC), either thyroid hormone withdrawal (THW) or administration of recombinant human thyrotropin (rhTSH) can be performed., Objective: Our objective is to compare quality of life (QoL) parameters using the SF-36v2 questionnaire (Short Form health survey) and a self-evaluated item, and the hypothyroid status using modified Billewicz scores in an Asian population undergoing either THW or rhTSH for remnant ablation or adjuvant treatment following total thyroidectomy for WDTC. We will also assess the proportion of patients achieving TSH level of >30 mU/L after 4 weeks of thyroid hormone withdrawal., Results: Patients in the rhTSH group were better in the QoL domains of physical functioning, role functioning/physical and bodily pain, while patients in THW group were better in mental health. This was however, not statistically significant. Modified Billewicz scores were higher in patients in THW group as compared with rhTSH group and statistically significant. A total of 96.3% of patients achieved TSH level >30 mU/L after 4 weeks of THW., Conclusion: Clinical symptoms and signs of hypothyroidism as assessed with modified Billewicz scores were statistically significantly higher in the THW group. However, there was no statistically significant difference in QoL in the rhTSH group.

Purpose: The aim of this short communication is to outline our experience in policies and processes of a nuclear medicine service during the COVID-19 outbreak in Singapore., Methods: We describe the key considerations of policies and processes that have been implemented in our nuclear medicine service since the first case of COVID-19 was confirmed in Singapore General Hospital on 23 January 2020, up to the present time., Results: Infection control, screening of patients and visitors, segregation of risk groups, segregation of staff and service continuity plans, communication and staff welfare, using electronic platforms for multi-disciplinary meetings and tele-reporting are discussed., Conclusion: Since our hospital received the first patient with COVID-19 in Singapore, our centre has managed 16 COVID-19 cases to date. There has not been any healthcare worker in our institution who has contracted COVID-19 through patient contact. We have highlighted for discussion some of the policies and processes to prepare a nuclear medicine service for the COVID-19 threat.

Background: Invasive Salmonella infections result in significant morbidity and mortality in developing countries. In Asia, typhoid and paratyphoid fever are reported to be the major invasive Salmonella infections, while invasive non-typhoidal Salmonella (iNTS) infections are believed to be uncommon. Data from Sarawak, in Malaysian Borneo, are limited., Methods: A retrospective study identifying all children aged < 15 years with invasive Salmonella infections from 2011 to 2016 was conducted in Bintulu Hospital in Sarawak. Population incidences, clinical and bacterial characteristics were examined., Results: Forty-four patients were identified during the 6-year study period: 43 had iNTS infection and 1 had typhoid fever. The average annual iNTS incidence was 32.4 per 100,000 children aged < 5 years. None of the children had malaria or HIV infection, and only 7% were severely malnourished. Salmonella Enteritidis and Salmonella Java were the commonest NTS serovars identified. Pneumonia was the most common manifestation of iNTS disease, present in 20 (47%) children. Other manifestations included gastroenteritis, fever without a source, septic arthritis and meningitis. Salmonella Enteritidis was identified in 76% of those with pneumonia, significantly more frequently than in children with other manifestations. Over 25% of children with iNTS developed severe disease and nearly 10% suffered long term morbidity or mortality. While 78% of Salmonella Java isolates were multi-drug resistant, nearly all other isolates were susceptible to most antimicrobials, including ampicillin., Conclusions: Bintulu Division in Sarawak observed a very high incidence of childhood iNTS infections. Enteric fever was uncommon. The epidemiology of invasive Salmonella infections in Malaysian Borneo differs considerably from that of neighbouring countries in Asia.

Objectives: Current cardiovascular disease (CVD) nutrition guidelines do not take into account Chinese medicine (CM) principles. We created a heart healthy integrative nutritional counseling (H2INC) curriculum consistent with CM principles and current nutrition guidelines., Methods: We conducted three phases of semi-structured interviews with key stakeholders (CM and biomedical providers and Chinese American (CAs) patients with CVD) followed by iterative development of H2INC. First, we interviewed licensed CM providers (n = 9) and laypeople with CM foods expertise (n = 1). Second, we interviewed biomedical providers (n = 11) and licensed CM providers (n = 3). Third, we conducted four focus groups with CAs (n = 20) with CVD., Results: Stakeholders emphasized different principles for creating H2INC. Phase one emphasized alignment of CM diagnoses to biomedical CVD conditions. Phase two overlaid CM concepts like the nature of foods and constitution (hot/neutral/cool) with heart healthy nutrition recommendations such as MyPlate, and avoiding excess salt, fat, and sugars. Phase three demonstrated patient acceptability., Conclusion: By integrating CM foods principles with biomedical nutrition, this integrative approach yields culturally relevant health education for an underserved population., Practice Implications: Integrative nutritional counseling shows promise for CAs and could support biomedical providers with little knowledge about patients' use of CM for CVD., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Systemic sclerosis-associated gastrointestinal tract involvement (SSc-GIT) is an independent predictor of 2-year mortality in early SSc. Availability of non-invasive investigations will facilitate early diagnosis and monitoring., Hypothesis: We investigate the role of 18 F-FDG-PET-MRI in SSc-GIT, hypothesizing that i) higher bowel FDG-PET uptake, a surrogate biomarker for inflammation, distinguishes healthy bowel from inflamed SSc-GIT; ii) MRI T1-MOLLI mapping, a surrogate biomarker for cardiac fibrosis, distinguishes healthy bowel from fibrotic SSc-GIT., Methods: In this prospective study, 16 SSc patients and 15 healthy controls were recruited. All SSc patients and 5 controls underwent PET-MRI (with T1-MOLLI mapping) on a Siemens 3T mMR; 10 controls underwent MRI without PET. Manual segmentation of the large and small bowels was performed jointly by two trained analysts in order to report T1 and PET values. Control dataset was used to assess normal healthy range. Mean T1 values, mean Tissue-to-Background (TBR) PET values, as well as amount of supposedly abnormal bowel (measured using the healthy ranges) was compared using Student's t-test and Cohen's d effect size., Results: Mean T1 values in large (1113 ± 182 ms vs 856 ± 176 ms; p-value < 0.001) and small bowel (1331 ± 239 ms vs 1169 ± 118 ms; p = 0.02) were higher in SSc patients than controls. 87.5% of the SSc patients' bowel had at least a grade 3 segmental FDG-PET uptake, while no controls showed more than a grade 2 segmental uptake. Patients had higher large bowel mean PET TBR (1.12 ± 0.22) than controls (0.82 ± 0.20, p = 0.02). Using PET and T1 thresholds defined using the control PET-MR data, the percentage of supposedly healthy (non-fibrotic and non-inflamed) tissue was significantly lower in SSc patients (81.1 ± 13.1%) than controls (95.7 ± 3.1%, p = 0.03) for the large bowel., Conclusion: Our novel study of FDG-PET-MRI in SSc-GIT demonstrated promising results in non-invasively evaluating concurrently bowel inflammation and fibrosis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Intravenous infusion of lignocaine has emerged in recent years as a feasible, cost-effective, and safe method to provide postoperative analgesia. There is, however, no literature about this perioperative pain control modality in Chinese patients. This study aimed to determine whether perioperative intravenous lignocaine safely reduces postoperative pain, shortens postoperative ileus, and reduces the length of hospital stay in laparoscopic colorectal surgery., Methods: Between September 2012 and May 2015, 16 patients who underwent elective laparoscopic resection of colorectal cancer and received a 1% lignocaine infusion for 24 hours postoperatively were studied. After surgery, categorical pain scores were obtained immediately, followed by hourly pain scores at rest. Pain scores at rest and with mobilisation, and patient satisfaction score were documented on postoperative day 1. Return of bowel function was measured by time of first flatus and bowel opening. The patient's rehabilitation was assessed by time taken to tolerate diet, full mobilisation, and length of hospital stay., Results: The median (interquartile range) self-reported pain scores at 2 hours and 6 hours after surgery were 1.5 (0-4) and 2 (0-3), respectively. The median pain scores at rest and mobilisation on postoperative day 1 were 1 (0-2.5) and 2 (2.5-5), respectively, with a median satisfaction score of 7.5 (7-9). The median times to first flatus and first bowel opening were 21 (18-35) hours and 3 (1-3) days, respectively. No patient had postoperative ileus. The median times to tolerating diet and mobilisation were 1 (1-1) day and 2 (2-3) days, respectively. The median postoperative stay was 6 (5-8) days., Conclusions: Intravenous lignocaine is a safe and effective postoperative analgesic in a Chinese population. It enhances the rehabilitation process for patients following laparoscopic resection of colorectal cancer.

Distant metastases change the prognosis of patients with nasopharyngeal carcinoma (NPC) which most commonly metastasizes to the bone. 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) is reported as useful in imaging NPC metastases. Our study assesses the incidence and distribution of bone metastases detected by 18 F-FDG PET/CT in NPC. 717 18 F-FDG PET/CT scan reports of histologically proven NPC patients imaged in Singapore General Hospital, Singapore, between 2003 and 2009 were reviewed for the total number of metastases (scanned from vertex to mid-thigh) and analyzed for distribution. Of the 709 FDG avid metastases in these reports, 357/709 (50.35%) were locoregional nodal metastasis and 352/709 (49.65%) were distant metastases of which 192/709 (27.08%) of total metastases and 54.54% of distant metastases (192/352) were in the bones. The majority of the bone lesions 125/192 (65.1%) were in the axial skeleton with 109/192 (56.77%) in the lower skeleton (thoracolumbar spine, sacrum, and pelvis). The incidence of bone metastases in our study (27.08%) was higher than that reported in other studies, for example, 15% by Liu et al . and 11% (230 patients) by Caglar et al . Bone metastases have been reported in the femurs and the feet and as such some metastases may have been outside the field of view of the scans. In our study, 27% of FDG avid NPC metastases are in the bones., Competing Interests: There are no conflicts of interest.

Neuroblastoma, the most common solid tumor of young children, frequently presents with aggressive metastatic disease and for these children the 5-year survival rates are dismal. Metastasis, the movement of cancer cells from one site to another, involves remodeling of the cytoskeleton including altered microtubule dynamics. The microtubule-destabilizing protein, stathmin, has recently been shown to mediate neuroblastoma metastasis although precise functions remain poorly defined. In this study we investigated stathmin's contribution to the metastatic process and potential mechanism(s) by which it exerts these effects. Stathmin suppression significantly reduced neuroblastoma cell invasion of 3D tumor spheroids into an extracellular matrix. Moreover, inhibiting stathmin expression significantly reduced transendothelial migration in two different neuroblastoma cell lines in vitro. Inhibition of ROCK, a key regulator of cell migration, in neuroblastoma cells highlighted that stathmin regulates transendothelial migration through ROCK signaling. Reduced stathmin expression in neuroblastoma cells significantly increased the activation of the RhoA small GTPase. Notably, re-expression of either wild type or a phospho-mimetic stathmin mutant (4E) made defective in tubulin binding returned cell migration and transendothelial migration back to control levels, indicating that stathmin may influence these processes in neuroblastoma cells independent of tubulin binding. Finally, stathmin suppression in neuroblastoma cells significantly reduced whole body, lung, kidney and liver metastases in an experimental metastases mouse model. In conclusion, stathmin suppression interferes with the metastatic process via RhoA/ROCK signaling in neuroblastoma cells. These findings highlight the importance of stathmin to the metastatic process and its potential as a therapeutic target for the treatment of neuroblastoma.

Mutations in WD40-repeat protein 62 ( WDR62 ) are commonly associated with primary microcephaly and other developmental cortical malformations. We used human pluripotent stem cells (hPSC) to examine WDR62 function during human neural differentiation and model early stages of human corticogenesis. Neurospheres lacking WDR62 expression showed decreased expression of intermediate progenitor marker, TBR2, and also glial marker, S100 β . In contrast, inhibition of c-Jun N-terminal kinase (JNK) signalling during hPSC neural differentiation induced upregulation of WDR62 with a corresponding increase in neural and glial progenitor markers, PAX6 and EAAT1, respectively. These findings may signify a role of WDR62 in specifying intermediate neural and glial progenitors during human pluripotent stem cell differentiation.

Proteomics plays an increasingly important role in our quest to understand cardiovascular biology. Fueled by analytical and computational advances in the past decade, proteomics applications can now go beyond merely inventorying protein species, and address sophisticated questions on cardiac physiology. The advent of massive mass spectrometry datasets has in turn led to increasing intersection between proteomics and big data science. Here we review new frontiers in technological developments and their applications to cardiovascular medicine. The impact of big data science on cardiovascular proteomics investigations and translation to medicine is highlighted.

Background: Approximately 20 % of hepatocellular carcinoma (HCC) patients diagnosed in the early stages may benefit from potentially curative ablative therapies such as surgical resection, transplantation or radiofrequency ablation. For patients not eligible for such options, prognosis is poor. Sorafenib and Selective Internal Radiation Therapy (SIRT) are clinically proven treatment options in patients with unresectable HCC, and this study aims to assess overall survival following either SIRT or Sorafenib therapy for locally advanced HCC patients., Methods: This investigator-initiated, multi-centre, open-label, randomized, controlled trial will enrol 360 patients with locally advanced HCC, as defined by Barcelona Clinic Liver Cancer stage B or stage C, without distant metastases, and which is not amenable to immediate curative treatment. Exclusion criteria include previous systemic therapy, metastatic disease, complete occlusion of the main portal vein, or a Child-Pugh score of >7. Eligible patients will be randomised 1:1 and stratified by centre and presence or absence of portal vein thrombosis to receive either a single administration of SIRT using yttrium-90 resin microspheres (SIR-Spheres®, Sirtex Medical Limited, Sydney, Australia) targeted at HCC in the liver by the trans-arterial route or continuous oral Sorafenib (Nexavar®, Bayer Pharma AG, Berlin, Germany) at a dose of 400 mg twice daily until disease progression, no further response, complete regression or unacceptable toxicity. Patients for both the Sorafenib and SIRT arms will be followed-up every 4 weeks for the first 3 months and 12 weekly thereafter. Overall survival is the primary endpoint, assessed for the intention-to-treat population. Secondary endpoints are tumour response rate, time-to-tumour progression, progression free survival, quality of life and down-staging to receive potentially curative therapy., Discussion: Definitive data comparing these two therapies will help to determine clinical practice in the large group of patients with locally advanced HCC and improve outcomes for such patients., Trial Registration: ClinicalTrials.gov identifier, NCT01135056 , first received 24, May 2010.

Amidst the proteomes of human tissues lie subsets of proteins that are closely involved in conserved pathophysiological processes. Much of biomedical research concerns interrogating disease signature proteins and defining their roles in disease mechanisms. With advances in proteomics technologies, it is now feasible to develop targeted proteomics assays that can accurately quantify protein abundance as well as their post-translational modifications; however, with rapidly accumulating number of studies implicating proteins in diseases, current resources are insufficient to target every protein without judiciously prioritizing the proteins with high significance and impact for assay development. We describe here a data science method to prioritize and expedite assay development on high-impact proteins across research fields by leveraging the biomedical literature record to rank and normalize proteins that are popularly and preferentially published by biomedical researchers. We demonstrate this method by finding priority proteins across six major physiological systems (cardiovascular, cerebral, hepatic, renal, pulmonary, and intestinal). The described method is data-driven and builds upon the collective knowledge of previous publications referenced on PubMed to lend objectivity to target selection. The method and resulting popular protein lists may also be useful for exploring biological processes associated with various physiological systems and research topics, in addition to benefiting ongoing efforts to facilitate the broad translation of proteomics technologies.

In recent years, yttrium-90 ((90)Y) microsphere radioembolization has been establishing itself as a safe and efficacious treatment for both primary and metastatic liver cancers. This extends to both first-line therapies as well as in the salvage setting. In addition, radioembolization appears efficacious for patients with portal vein thrombosis, which is currently a contraindication for surgery, transplantation and transarterial chemoembolization. This article reviews the efficacy and expanding use of (90)Y microsphere radioembolization with an added emphasis on recent advances in personalized dosimetry and interventional radiology techniques. Directions for future research into combination therapies with radioembolization and expansion into sites other than the liver are also explored.

Chikungunya fever (CHIKF) is a global infectious disease which can affect a wide range of age groups. The pathological and immunological response upon Chikungunya virus (CHIKV) infection have been reported over the last few years. However, the clinical profile and immune response upon CHIKV infection in children remain largely unknown. In this study, we analyzed the clinical and immunological response, focusing on the cytokine/chemokine profile in a CHIKV-infected pediatric cohort from Sarawak, Malaysia. Unique immune mediators triggered upon CHIKV infection were identified through meta-analysis of the immune signatures between this pediatric group and cohorts from previous outbreaks. The data generated from this study revealed that a broad spectrum of cytokines/chemokines is up-regulated in a sub-group of virus-infected children stratified according to their viremic status during hospitalization. Furthermore, different immune mediator profiles (the levels of pro-inflammatory cytokines, chemokines and growth and other factors) were observed between children and adults. This study gives an important insight to understand the immune response of CHIKV infection in children and would aid in the development of better prognostics and clinical management for children.

Introduction: A paradigm shift appears to have occurred worldwide in surgery for primary hyperparathyroidism with the advent of sensitive preoperative imaging techniques. Preoperative imaging for parathyroid adenoma localisation was not found to be useful in a study conducted in Singapore in the 1990s. This study aimed to explore what the change has been in preoperative localisation tools compared to the previous study and if the ability of these tools to correctly localise pathologic parathyroid glands has improved., Materials and Methods: A retrospective review of patients who had surgery for primary hyperparathyroidism at our institution during the period 2005 to 2014 was carried out. Individuals with positive, as opposed to those with negative preoperative imaging, were compared with regard to whether they underwent limited focal or bilateral neck exploration. Length of hospital stay (LOHS) was also compared between patients who underwent limited versus bilateral exploration., Results: Fifty-eight patients who had preoperative imaging and surgery were evaluated. True positive rates of sestamibi, ultrasound and 4-dimensional (4D) computed tomography (CT) scans were 63.8%, 72.4% and 90%, respectively. Eighty percent of patients who had positive localisation had limited exploration. LOHS was 2.8 days (1.6, 4.8) and 4.3 days (2.1, 9.0) for limited and bilateral exploration respectively, P = 0.011., Conclusion: Our study highlights the marked change in the surgical landscape for primary hyperparathyroidism in the last 2 decades in Singapore. Improved preoperative localisation has resulted in a swing from predominantly bilateral, to limited exploration in almost all cases of primary hyperparathyroidism due to solitary adenoma. LOHS was significantly shorter in patients who had limited as compared to those who had bilateral exploration.

An expert panel met to review the evidence for selective internal radiation therapy (SIRT) using yttrium-90 microspheres in hepatocellular carcinoma and metastases from colorectal cancer and neuroendocrine tumors. There is now convincing evidence for the safety and efficacy of SIRT in these situations albeit mostly from retrospective cohort studies. There are a number of ongoing prospective randomized controlled clinical trials investigating the role of SIRT in liver tumors; however, data from these trials are still several years away (although the SIRFLOX study has been recently published). In this evolving environment, published evidence and the authors' experience were used to summarize the current and potential role of SIRT in the management of hepatocellular carcinoma of intermediate or advanced stage and in liver-dominant metastatic colorectal cancer and metastatic neuroendocrine tumors.

Excitotoxicity, a pathological process caused by over-stimulation of ionotropic glutamate receptors, is a major cause of neuronal loss in acute and chronic neurological conditions such as ischaemic stroke, Alzheimer's and Huntington's diseases. Effective neuroprotective drugs to reduce excitotoxic neuronal loss in patients suffering from these neurological conditions are urgently needed. One avenue to achieve this goal is to clearly define the intracellular events mediating the neurotoxic signals originating from the over-stimulated glutamate receptors in neurons. In this review, we first focus on the key cellular events directing neuronal death but not involved in normal physiological processes in the neurotoxic signalling pathways. These events, referred to as pathologically activated events, are potential targets for the development of neuroprotectant therapeutics. Inhibitors blocking some of the known pathologically activated cellular events have been proven to be effective in reducing stroke-induced brain damage in animal models. Notable examples are inhibitors suppressing the ion channel activity of neurotoxic glutamate receptors and those disrupting interactions of specific cellular proteins occurring only in neurons undergoing excitotoxic cell death. Among them, Tat-NR2B9c and memantine are clinically effective in reducing brain damage caused by some acute and chronic neurological conditions. Our second focus is evaluation of the suitability of the other inhibitors for use as neuroprotective therapeutics. We also discuss the experimental approaches suitable for bridging our knowledge gap in our current understanding of the excitotoxic signalling mechanism in neurons and discovery of new pathologically activated cellular events as potential targets for neuroprotection., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Hepatocellular carcinoma (HCC) is the 6th most common cancer in the world, but the second most common cause of cancer death. There is no universally accepted consensus practice guidelines for HCC owing to rapid developments in new treatment modalities, the heterogeneous epidemiology and clinical presentation of HCC worldwide. However, a number of regional and national guidelines currently exist which reflect practice relevant to the epidemiology and collective experience of the consensus group. In 2014, clinicians at the multidisciplinary Comprehensive Liver Cancer Clinic (CLCC) at the National Cancer Centre Singapore (NCCS) reviewed the latest published scientific data and existing international and regional practice guidelines, such as those of the National Comprehensive Cancer Network, American Association for the Study of Liver Diseases and the Asian Pacific Association for the Study of the Liver, and modified them to reflect local practice. These would serve as a template by which treatment outcomes can be collated and benchmarked against international data. The NCCS Consensus Guidelines for HCC have been successfully implemented in the CLCC since their publication online on 26(th) September 2014, and the guidelines allow outcomes of treatment to be compared to international data. These guidelines will be reviewed periodically to incorporate new data.

Protein stability is a major regulatory principle of protein function and cellular homeostasis. Despite limited understanding on mechanisms, disruption of protein turnover is widely implicated in diverse pathologies from heart failure to neurodegenerations. Information on global protein dynamics therefore has the potential to expand the depth and scope of disease phenotyping and therapeutic strategies. Using an integrated platform of metabolic labeling, high-resolution mass spectrometry and computational analysis, we report here a comprehensive dataset of the in vivo half-life of 3,228 and the expression of 8,064 cardiac proteins, quantified under healthy and hypertrophic conditions across six mouse genetic strains commonly employed in biomedical research. We anticipate these data will aid in understanding key mitochondrial and metabolic pathways in heart diseases, and further serve as a reference for methodology development in dynamics studies in multiple organ systems.