Validation of the International Myositis Assessment and Clinical Studies Group guideline on cancer risk stratification.

OBJECTIVES: Adult-onset Idiopathic inflammatory myopathies (IIMs) are associated with cancer. Guideline on cancer risk stratifications and screening in IIM patients was recently published, but their external validity remains verified. We evaluated its applicability and reliability among a Hong Kong IIM cohort. METHODS: The longitudinal observational cohort collected data from IIM patients fulfilling relevant classification criteria from 8 rheumatology centres in Hong Kong. Demographic, clinical and laboratory data were reviewed from 2004-2023. IIM patients were stratified into standard, intermediate or high-risk subgroups according to the IMACS guideline. The occurrence of malignancy at or after IIM diagnosis was analyzed. Independent risk factors for cancer were evaluated. RESULTS: 479 patients were included with 327 females (68.3%) and mean age of IIM diagnosis at 54.5 ± 13.6 years. 214 (44.7%) and 238 (49.7%) patients were stratified to high and intermediate risk groups, respectively. Only 5.6% belonged to the standard-risk group. 60 patients (12.5%) had cancer within 3 years of IIM diagnosis. Nasopharyngeal (25%), lung (21.1%) and breast (10.5%) were the top 3 cancers. Significantly more patients (44, 20.6%) in the high-risk group developed cancer within 3 years, compared with intermediate (6.7%, p< 0.001) and standard-risk (0%, p= 0.009) groups. Risk factors for cancer included older age (OR : 1.048, 95%CI : 1.019-1.078), Gottron's rash (OR : 2.453, 95%CI : 1.123-5.356), absence of ILD (OR 2.695, 95% CI : 1.154-6.295), anti-TIF1g positivity (OR : 4.627, 95% CI : 2.046-10.461) and anti-SAE1 positivity (OR : 5.325, 95% CI : 1.271-22.300). CONCLUSIONS: Our real-world study supported the accuracy of cancer risk stratification. Vast majority of IIM patients would be subjected to extensive cancer screening when the guideline was applied.

MDF-Net: A Multi-Scale Dynamic Fusion Network for Breast Tumor Segmentation of Ultrasound Images.

Breast tumor segmentation of ultrasound images provides valuable information of tumors for early detection and diagnosis. Accurate segmentation is challenging due to low image contrast between areas of interest; speckle noises, and large inter-subject variations in tumor shape and size. This paper proposes a novel Multi-scale Dynamic Fusion Network (MDF-Net) for breast ultrasound tumor segmentation. It employs a two-stage end-to-end architecture with a trunk sub-network for multiscale feature selection and a structurally optimized refinement sub-network for mitigating impairments such as noise and inter-subject variation via better feature exploration and fusion. The trunk network is extended from UNet++ with a simplified skip pathway structure to connect the features between adjacent scales. Moreover, deep supervision at all scales, instead of at the finest scale in UNet++, is proposed to extract more discriminative features and mitigate errors from speckle noise via a hybrid loss function. Unlike previous works, the first stage is linked to a loss function of the second stage so that both the preliminary segmentations and refinement subnetworks can be refined together at training. The refinement sub-network utilizes a structurally optimized MDF mechanism to integrate preliminary segmentation information (capturing general tumor shape and size) at coarse scales and explores inter-subject variation information at finer scales. Experimental results from two public datasets show that the proposed method achieves better Dice and other scores over state-of-the-art methods. Qualitative analysis also indicates that our proposed network is more robust to tumor size/shapes, speckle noise and heavy posterior shadows along tumor boundaries. An optional post-processing step is also proposed to facilitate users in mitigating segmentation artifacts. The efficiency of the proposed network is also illustrated on the "Electron Microscopy neural structures segmentation dataset". It outperforms a state-of-the-art algorithm based on UNet-2022 with simpler settings. This indicates the advantages of our MDF-Nets in other challenging image segmentation tasks with small to medium data sizes.

Challenges for Liver Transplantation During Recovery From the COVID-19 Pandemic: Insights and Recommendations.

The coronavirus disease 2019 (COVID-19) pandemic is placing an increasing burden on liver transplant (LT) services worldwide. At the peak of the pandemic, many LT services worldwide reduced or halted their activities. With the gradual easing of lockdowns, LT teams face new challenges when restarting activities. The numbers of LTs are likely to drop in the immediate post-COVID era. Prolonged and intermittent lockdowns are likely to lead to a shortage of supplies, especially in poor resource settings. Special attention is needed to avoid nosocomial COVID-19 infection among cirrhotic patients awaiting transplant, post-transplant patients, and members of transplant teams. LT programs may have to revise existing strategies in selecting donors and recipients for transplants. Redesigning service provision, restructuring outpatient care, carefully screening and selecting donors and recipients, and performing LT with limited resources will have to be initiated in the post-COVID era if long-term recovery of LT services is to be expected. Costs involved with LT are likely to increase, considering the change in protocols of testing, quarantining, and interstate traveling. This paper discusses the different elements affecting and the widespread impact of the COVID-19 pandemic on LT and strategies to minimize the impact of these factors and to adapt so LT services can meet the health care needs during this pandemic and beyond.

Hepatitis B Vaccination in Patients Receiving Oral Antiviral Therapy Without Hepatitis B Immunoglobulin After Liver Transplant.

Our study aimed to determine if a double-dose pre-S containing hepatitis B virus (HBV) vaccination (Sci-B-Vac) could elicit an adequate and sustainable immune response in HBV patients who developed spontaneous hepatitis B surface antibody (anti-HBs) response after liver transplant. PATIENTS AND METHODS: All patients who received transplants for HBV-related disease for >1 year with normal graft function and hepatitis B surface antigen seronegativity were evaluated. They received a 40-µg HBV vaccine if they were responders in our previous vaccine trial, if anti-HBs was positive for >1 year after liver transplant (LT), or if a peak anti-HBs at any time point after LT was >100 mIU/mL. Primary endpoint was the development of anti-HBs ≥ 10 mIU/mL from previous negative value or a 1-log increase from baseline. RESULTS: A total of 86 patients were recruited; 5 were responders from a previous trial; 45 patients had detectable anti-HBs >1 year after LT, and 36 patients had an anti-HBs >100 mIU/mL. All (5/5, 100%) previous responders responded to booster vaccination. For the remaining 81 patients, 10 of 81 (12.3%) responded. CONCLUSION: All previous responders responded to booster vaccination, implying durability and memory of HBV immune response, which is an important prerequisite for definitive host immunity for HBV. In patients who had spontaneous anti-HBs production after LT, a single vaccination can induce response in 12.3% of patients.

A New Probabilistic Representation of Color Image Pixels and Its Applications.

This paper proposes a novel probabilistic representation of color image pixels (PRCI) and investigates its applications to similarity construction in motion estimation and image segmentation problems. The PRCI explores the mixture representation of the input image(s) as prior information and describes a given color pixel in terms of its membership in the mixture. Such representation greatly simplifies the estimation of the probability density function from limited observations and allows us to derive a new probabilistic pixel-wise similarity measure based on the continuous domain Bhattacharyya coefficient. This yields a convenient expression of the similarity measure in terms of the pixel memberships. Furthermore, this pixel-wise similarity is extended to measure the similarity between two image regions. The usefulness of the proposed pixel/region-wise similarities is demonstrated by incorporating them respectively in a dense image descriptor-based multi- layered motion estimation problem and an unsupervised image segmentation problem. Experimental results show that i) the integration of the proposed pixel-wise similarity in dense image-descriptor construction yields improved peak signal to noise ratio performance and higher tracking accuracy in the multi-layered motion estimation problem, and ii) the proposed similarity measures give the best performance in terms of all quantitative measurements in the unsupervised superpixel- based image segmentation of the MSRC and BSD300 datasets.

Introduction to the Issue on Physics and Applications of Laser Dynamics (IS-PALD 2017).

In this paper, we introduce the Optics Express feature issue of the 7th International Symposium on Physics and Applications of Laser Dynamics (IS-PALD). This issue consists of expanded papers related to oral and poster presentations. Selected papers represent the best of IS-PALD 2017.

Impact of pharmacist-involved collaborative care on the clinical, humanistic and cost outcomes of high-risk patients with type 2 diabetes (IMPACT): a randomized controlled trial.

WHAT IS KNOWN AND OBJECTIVE: With the increasing prevalence of diabetes, the physician-centred model is challenged to deliver holistic care in Asia. Diabetes may be managed effectively within a multidisciplinary collaborative care model; however, evidence on its effectiveness in Asian patients is lacking. Therefore, the primary objective was to evaluate the clinical outcomes of multidisciplinary collaborative care vs physician-centred care in diabetes. The secondary objectives were to evaluate humanistic and economic outcomes among the two types of care. METHODS: This 6-month prospective, open-label, parallel-arm, randomized, controlled study was conducted at four outpatient healthcare institutions. High-risk patients aged ≥21 years with uncontrolled type 2 diabetes, polypharmacy and comorbidities were included. Patients with type 1 diabetes or those who were unable to communicate independently were excluded. The control arm received usual care with referrals to nurses and dietitians as needed. The intervention arm (multidisciplinary collaborative care) was followed up with pharmacists regularly, in addition to receiving the usual care. The primary outcomes included HbA1c, systolic blood pressure, low-density lipoprotein and triglycerides. The secondary outcomes included scores from the Problem Areas in Diabetes (PAID) and the Diabetes Treatment Satisfaction Questionnaires (DTSQ), and diabetes-related health service utilization rates and costs. RESULTS AND DISCUSSION: Of 411 eligible patients, 214 and 197 patients were randomized into the intervention and control arms, respectively. At 6 months, 141 patients in the intervention arm (65.9%) and 189 patients in the control arm (95.9%) completed the study. Mean HbA1c reduced from 8.6%±1.5% at baseline to 8.1%±1.3% at 6 months in the intervention arm (P=.04), with up to mean HbA1c improvement of 0.8% in patients with greater levels of uncontrolled glycemia. Whereas the mean HbA1c in the control arm remained unchanged (8.5%±1.4%) throughout the 6-month period. Improvements in PAID and DTSQ scores, reduction in physician workload and an average cost savings of US$91.01 per patient were observed in the intervention arm over 6 months. WHAT IS NEW AND CONCLUSIONS: The positive clinical, humanistic and economic outcomes highlighted the value of multidisciplinary collaborative care for Asian diabetic patients, thereby supporting the effectiveness of this approach in managing chronic diseases.

The BMP2 variant L51P restores the osteogenic differentiation of human mesenchymal stromal cells in the presence of intervertebral disc cells.

Spinal fusion is hampered by the presence of remaining intervertebral disc (IVD) tissue and leads to spinal non-union. While the exact mechanism remains unknown, we hypothesise that factors preventing disc ossification, such as antagonists of the bone morphogenetic proteins (BMP), could be responsible for this process. The objective of this study was to investigate spinal non-union using an in vitro human model with a focus on the BMP signalling components and to identify factors contributing to the incomplete and delayed ossification. Human bone marrow-derived mesenchymal stromal cells (MSC) were cocultured with IVD cells in the presence of L51P, a BMP2 variant with osteoinductive potential. The ossification of MSC was evaluated by quantitative reverse transcription polymerase chain reaction (qPCR), alkaline phosphatase (ALP) activity and alizarin red staining. Endogenous expression of major BMP antagonists, namely Gremlin (GREM1), Noggin (NOG) and Chordin (CHRD) was detected in IVD-derived cells, with abundance in nucleus pulposus cells. Osteogenesis of MSC was hindered by IVD cells as shown by reduced alizarin red staining, ALP activity and qPCR. L51P, added to the cocultures, restored mineralisation, blocking the activity of the BMP antagonists secreted by IVD cells. It is possible that the BMP antagonists secreted by IVD cells are responsible for spinal non-unions. The inhibition of BMP antagonists with L51P may result in an efficient and more physiological osteoinduction rather than delivery of exogenous osteogenic factors. Therefore, L51P might represent an attractive therapeutic candidate for bone healing.

Inhibitor development after liver transplantation in congenital factor VII deficiency.

Congenital factor VII (FVII) deficiency is the commonest type of the rare bleeding disorders. Very few cases of congenital FVII deficiency developed inhibitor and liver transplant is considered as definitive treatment. In the literature, twelve patients with congenital FVII deficiency developed inhibitors. Two had spontaneous resolution of inhibitors and one did not respond to high dose recombinant factor VIIa (rFVIIa) and died. Regarding liver transplant in congenital FVII patients, seven patients underwent liver transplant with good prognosis. We report a 5-year-old girl with confirmed severe congenital FVII deficiency since neonatal period. She suffered from recurrent intracranial bleeding despite rFVIIa replacement. After auxiliary liver transplant at the age of 4, she continued to show persistent deranged clotting profile and was found to have inhibitor towards FVII. Interestingly, she was still responsive to rFVIIa replacement.

Implementing standard setting into the Conjoint MAFP/FRACGP Part 1 examination - Process and issues.

BACKGROUND: The College of General Practitioners of Malaysia and the Royal Australian College of General Practitioners held the first Conjoint Member of the College of General Practitioners (MCGP)/Fellow of Royal Australian College of General Practitioners (FRACGP) examination in 1982, later renamed the Conjoint MAFP/FRACGP examinations. The examination assesses competency for safe independent general practice and as family medicine specialists in Malaysia. Therefore, a defensible standard set pass mark is imperative to separate the competent from the incompetent. OBJECTIVE: This paper discusses the process and issues encountered in implementing standard setting to the Conjoint Part 1 examination. DISCUSSION: Critical to success in standard setting were judges' understanding of the process of the modified Angoff method, defining the borderline candidate's characteristics and the composition of judges. These were overcome by repeated hands-on training, provision of detailed guidelines and careful selection of judges. In December 2013, 16 judges successfully standard set the Part 1 Conjoint examinations, with high inter-rater reliability: Cronbach's alpha coefficient 0.926 (Applied Knowledge Test), 0.921 (Key Feature Problems).

Case Report of Relay Liver Transplantation With Graft Infected With Hepatitis B Virus.

Reuse of liver graft for transplantation is extremely uncommon. We report the 1st case of reuse of liver graft from a recipient who had hepatitis B virus (HBV) infection, 11 years after the 1st transplantation. Our relay liver transplantation challenged conventional thinking because of late reuse of graft in the presence of HBV infection. Moreover, both the 1st and the 2nd donors were of advanced age. The key questions were whether the liver graft could be reused safely, especially in the setting of HBV infection, and technical concerns during organ procurement and implantation. The absence of HBV replication was confirmed with negative hepatitis B surface antigen and undetectable serum HBV DNA in the 2nd donor. Based on our experience in managing HBV infection after liver transplantation, we were confident that the adequately suppressed HBV infection in the donor would not jeopardize graft function and that the graft would be able to withstand another ischemia-perfusion injury to continue to function well in our recipient.

Rare cause of jaundice in a post liver transplant patient.

A hepatitis B virus carrier suffering from acute flare of chronic hepatitis B infection underwent deceased-donor liver transplantation. He was put on the immunosuppressive agent tacrolimus. On routine follow-up, he was found to have abnormal liver function. Computed tomography scan of the abdomen did not show any dilatation of the biliary system. Liver biopsy showed scattered microabscesses, and a microgranuloma was detected. Endoscopic retrograde cholangiography was performed and a biliary anastomotic stricture (BAS) was noted. In addition, the Chinese liver fluke, Clonorchis sinensis, was discovered. Balloon dilatation and stenting were performed. The patient was given a course of praziquantel. His liver function improved and normalized. We present the case of a liver transplant recipient with cholangitis caused by C. sinensis infestation and infection and biliary obstruction resulting from BAS.

A papain-induced disc degeneration model for the assessment of thermo-reversible hydrogel-cells therapeutic approach.

Nucleus pulposus (NP) regeneration by the application of injectable cell-embedded hydrogels is an appealing approach for tissue engineering. We investigated a thermo-reversible hydrogel (TR-HG), based on a modified polysaccharide with a thermo-reversible polyamide [poly(N-isopropylacrylamide), pNIPAM], which is made to behave as a liquid at room temperature and hardens at > 32 °C. In order to test the hydrogel, a papain-induced bovine caudal disc degeneration model (PDDM), creating a cavity in the NP, was employed. Human mesenchymal stem cells (hMSCs) or autologous bovine NP cells (bNPCs) were seeded in TR-HG; hMSCs were additionally preconditioned with rhGDF-5 for 7 days. Then, TR-HG was reversed to a fluid and the cell suspension injected into the PDDM and kept under static loading for 7 days. Experimental design was: (D1) fresh disc control + PBS injection; (D2) PDDM + PBS injection; (D3) PDDM + TR-HG (material control); (D4) PDDM + TR-HG + bNPCs; (D5) PDDM + TR-HG + hMSCs. Magnetic resonance imaging performed before and after loading, on days 9 and 16, allowed imaging of the hydrogel-filled PDDM and assessment of disc height and volume changes. In gel-injected discs the NP region showed a major drop in volume and disc height during culture under static load. The RT-PCR results of injected hMSCs showed significant upregulation of ACAN, COL2A1, VCAN and SOX9 during culture in the disc cavity, whereas the gene expression profile of NP cells remained unchanged. The cell viability of injected cells (NPCs or hMSCs) was maintained at over 86% in 3D culture and dropped to ~72% after organ culture. Our results underline the need for load-bearing hydrogels that are also cyto-compatible.

A forced running wheel system with a microcontroller that provides high-intensity exercise training in an animal ischemic stroke model

We developed a forced non-electric-shock running wheel (FNESRW) system that provides rats with high-intensity exercise training using automatic exercise training patterns that are controlled by a microcontroller. The proposed system successfully makes a breakthrough in the traditional motorized running wheel to allow rats to perform high-intensity training and to enable comparisons with the treadmill at the same exercise intensity without any electric shock. A polyvinyl chloride runway with a rough rubber surface was coated on the periphery of the wheel so as to permit automatic acceleration training, and which allowed the rats to run consistently at high speeds (30 m/min for 1 h). An animal ischemic stroke model was used to validate the proposed system. FNESRW, treadmill, control, and sham groups were studied. The FNESRW and treadmill groups underwent 3 weeks of endurance running training. After 3 weeks, the experiments of middle cerebral artery occlusion, the modified neurological severity score (mNSS), an inclined plane test, and triphenyltetrazolium chloride were performed to evaluate the effectiveness of the proposed platform. The proposed platform showed that enhancement of motor function, mNSS, and infarct volumes was significantly stronger in the FNESRW group than the control group (P<0.05) and similar to the treadmill group. The experimental data demonstrated that the proposed platform can be applied to test the benefit of exercise-preconditioning-induced neuroprotection using the animal stroke model. Additional advantages of the FNESRW system include stand-alone capability, independence of subjective human adjustment, and ease of use.

A forced running wheel system with a microcontroller that provides high-intensity exercise training in an animal ischemic stroke model.

We developed a forced non-electric-shock running wheel (FNESRW) system that provides rats with high-intensity exercise training using automatic exercise training patterns that are controlled by a microcontroller. The proposed system successfully makes a breakthrough in the traditional motorized running wheel to allow rats to perform high-intensity training and to enable comparisons with the treadmill at the same exercise intensity without any electric shock. A polyvinyl chloride runway with a rough rubber surface was coated on the periphery of the wheel so as to permit automatic acceleration training, and which allowed the rats to run consistently at high speeds (30 m/min for 1 h). An animal ischemic stroke model was used to validate the proposed system. FNESRW, treadmill, control, and sham groups were studied. The FNESRW and treadmill groups underwent 3 weeks of endurance running training. After 3 weeks, the experiments of middle cerebral artery occlusion, the modified neurological severity score (mNSS), an inclined plane test, and triphenyltetrazolium chloride were performed to evaluate the effectiveness of the proposed platform. The proposed platform showed that enhancement of motor function, mNSS, and infarct volumes was significantly stronger in the FNESRW group than the control group (P<0.05) and similar to the treadmill group. The experimental data demonstrated that the proposed platform can be applied to test the benefit of exercise-preconditioning-induced neuroprotection using the animal stroke model. Additional advantages of the FNESRW system include stand-alone capability, independence of subjective human adjustment, and ease of use.

Does diabetic status in the ICU predict haemofiltration requirement? The haemofiltration in the ICU and diabetic status (HIDS) study.

Diabetes is already a major health burden and prevalence is expected to double by 2025. The impact of diabetes and clinical outcomes in the intensive care unit is an evolving area of research. This study seeks to identify whether diabetic status is an independent risk factor for haemofiltration. This is a retrospective cohort study. All unique patients from a seven-year period from 2004 to 2010 at a major intensive care unit in Melbourne, Australia were analysed using multivariate regression to look for an association between diabetic status and haemofiltration. After exclusion criteria there were 7262 patients, 1674 with a history of diabetes (median age of 69, 66.72% male) and 5588 without a history of diabetes (median age 64, 64.13% male). Diabetic status was an independent risk factor (odds ratio 1.401, 95% confidence interval 1.079 to 1.820, P=0.011) for haemofiltration. Further research may identify intensive care unit-based renoprotective measures specifically for patients with diabetes.