Factors associated with in-hospital mortality among infective endocarditis patients.

INTRODUCTION: Despite recent advancements in the diagnosis and management of infective endocarditis (IE), it is associated with substantial morbidity and mortality. Our study objective is to determine the factors associated with in-hospital mortality in IE patients among the local population. MATERIALS AND METHODS: All IE patients who were diagnosed with definite or possible IE and were treated at Sarawak Heart Centre from 1st January 2020 to 31st December 2022 were recruited. We examined the demographic features of the subjects and the factors that contributed to in-hospital mortality. Multivariate logistic regression was used to analyse the associated factors and in-hospital mortality. RESULTS: Our study population comprised a total of 37 patients with a mean age of 46.4 years and male predominance. The in-hospital mortality rate of IE in this study was 44.4%. Haemodynamic instability and anaemia were found to be strong predictors of IE survival outcome, with an odds ratio of 51.5 and 35.7 respectively. Patients with vascular phenomenon and heart failure were at 10.5- and 6.0-times higher odds of dying, however, these two associations were found to be not statistically significant. CONCLUSION: The in-hospital mortality due to IE in our study was among the highest in developing countries. Factors of hypotension and optimal response to individual hemodynamic parameters may confer lower mortality. While anaemia is demonstrable as a risk factor for inpatient mortality, a target has yet to be reasonably established.

Molecular patterns of response and treatment failure after frontline venetoclax combinations in older patients with AML.

The BCL-2 inhibitor venetoclax combined with hypomethylating agents or low-dose cytarabine represents an important new therapy for older or unfit patients with acute myeloid leukemia (AML). We analyzed 81 patients receiving these venetoclax-based combinations to identify molecular correlates of durable remission, response followed by relapse (adaptive resistance), or refractory disease (primary resistance). High response rates and durable remissions were typically associated with NPM1 or IDH2 mutations, with prolonged molecular remissions prevalent for NPM1 mutations. Primary and adaptive resistance to venetoclax-based combinations was most commonly characterized by acquisition or enrichment of clones activating signaling pathways such as FLT3 or RAS or biallelically perturbing TP53. Single-cell studies highlighted the polyclonal nature of intratumoral resistance mechanisms in some cases. Among cases that were primary refractory, we identified heterogeneous and sometimes divergent interval changes in leukemic clones within a single cycle of therapy, highlighting the dynamic and rapid occurrence of therapeutic selection in AML. In functional studies, FLT3 internal tandem duplication gain or TP53 loss conferred cross-resistance to both venetoclax and cytotoxic-based therapies. Collectively, we highlight molecular determinants of outcome with clinical relevance to patients with AML receiving venetoclax-based combination therapies.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis treatment and follow-up of patients with localised colon cancer.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of localised colon cancer was published in 2020. It was decided by both the ESMO and the Japanese Society of Medical Oncology (JSMO) to convene a special virtual guidelines meeting in March 2021 to adapt the ESMO 2020 guidelines to take into account the ethnic differences associated with the treatment of localised colon cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with localised colon cancer representing the oncological societies of Japan (JSMO), China (CSCO), India (ISMPO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug availability and reimbursement situations in the different Asian countries.

Comparison of two different optical coherence tomography angiography devices in detecting healthy versus glaucomatous eyes - an observational cross-sectional study.

BACKGROUND: To understand the differences between two different optical coherence tomography angiography (OCTA) devices in detecting glaucomatous from healthy eyes by comparing their vascular parameters, diagnostic accuracy and test-retest reliability. METHODS: A cross-sectional observational study was performed on healthy and glaucoma subjects, on whom two sets of OCTA images of optic disc and macula were acquired using both AngioVue (Optovue, USA) and Swept Source (Topcon, Japan) OCTA devices during one visit. A novel in-house software was used to calculate the vessel densities. Diagnostic accuracy of the machines in differentiating healthy versus glaucomatous eyes was determined using area under the receiver operating characteristic curve (AUROC) and test-retest repeatability of the machines was also evaluated. RESULTS: A total of 80 healthy and 38 glaucomatous eyes were evaluated. Glaucomatous eyes had reduced mean vessel density compared to healthy controls in all segmented layers of the optic disc and macula using AngioVue (p ≤ 0.001). However, glaucomatous eyes had higher mean vessel density on optic disc scans using Swept Source, with lack of statistically significant difference between healthy and glaucomatous eyes. The AUROC showed better diagnostic accuracy of AngioVue (0.761-1.000) compared to Swept Source (0.113-0.644). The test-retest reliability indices were generally better using AngioVue than Swept Source. CONCLUSIONS: AngioVue showed better diagnostic capability and test-retest reliability compared to Swept Source. Further studies need to be undertaken to evaluate if there is any significant difference between the various machines in diagnosing and monitoring glaucoma.

The combined diabetes and renal control trial (C-DIRECT) - a feasibility randomised controlled trial to evaluate outcomes in multi-morbid patients with diabetes and on dialysis using a mixed methods approach.

BACKGROUND: This cluster randomised controlled trial set out to investigate the feasibility and acceptability of the "Combined Diabetes and Renal Control Trial" (C-DIRECT) intervention, a nurse-led intervention based on motivational interviewing and self-management in patients with coexisting end stage renal diseases and diabetes mellitus (DM ESRD). Its efficacy to improve glycaemic control, as well as psychosocial and self-care outcomes were also evaluated as secondary outcomes. METHODS: An assessor-blinded, clustered randomised-controlled trial was conducted with 44 haemodialysis patients with DM ESRD and ≥ 8% glycated haemoglobin (HbA1c), in dialysis centres across Singapore. Patients were randomised according to dialysis shifts. 20 patients were assigned to intervention and 24 were in usual care. The C-DIRECT intervention consisted of three weekly chair-side sessions delivered by diabetes specialist nurses. Data on recruitment, randomisation, and retention, and secondary outcomes such as clinical endpoints, emotional distress, adherence, and self-management skills measures were obtained at baseline and at 12 weeks follow-up. A qualitative evaluation using interviews was conducted at the end of the trial. RESULTS: Of the 44 recruited at baseline, 42 patients were evaluated at follow-up. One patient died, and one discontinued the study due to deteriorating health. Recruitment, retention, and acceptability rates of C-DIRECT were generally satisfactory HbA1c levels decreased in both groups, but C-DIRECT had more participants with HbA1c < 8% at follow up compared to usual care. Significant improvements in role limitations due to physical health were noted for C-DIRECT whereas levels remained stable in usual care. No statistically significant differences between groups were observed for other clinical markers and other patient-reported outcomes. There were no adverse effects. CONCLUSIONS: The trial demonstrated satisfactory feasibility. A brief intervention delivered on bedside as part of routine dialysis care showed some benefits in glycaemic control and on QOL domain compared with usual care, although no effect was observed in other secondary outcomes. Further research is needed to design and assess interventions to promote diabetes self-management in socially vulnerable patients. TRIAL REGISTRATION NUMBER: Trial registered with the International Standard Randomised Controlled Trial (ISRCTN10546597). Registered 12 September 2016 (Retrospectively registered).

Investigation of the size effect for photonic crystals.

Three types of photonic crystal (PC) thin films have been prepared for the investigation of their deformation behaviors by nanoindentation tests at the microscale and nanoscale. Each type of PC thin film was composed of poly(methyl methacrylate) (PMMA) nanoparticles with a uniform size. Another type of thin film was prepared by assembling nanoparticles with three different sizes. It was exciting to observe that the hardness and Young's modulus were significantly improved (more than 15 times) in well-ordered PC thin films than disordered ones. Furthermore, size-dependent mechanical properties were observed for the three types of PCs. Such a size effect phenomenon can be attributed to the special polycrystalline material having a periodical face-centered cubic structure of PC thin films. Furthermore, the indentation size effect that shows that the indentation hardness decreases with an increasing indentation depth has also been observed for all four types of thin films. It is conjectured that the application of the PC structure to other functional materials may enhance their mechanical properties.

The removal of metallic single-walled carbon nanotubes using an aqueous two-phase system.

Here we report our findings on the removal of metallic single-walled carbon nanotubes using an aqueous two-phase system. The aqueous two-phase system contained as received carbon nanotubes, polyethylene glycol, dextran, N-methylpyrrolidone, cetyltrimethylammonium bromide, and water which phase separated into top and bottom phases. The top phase was dominated by polyethylene glycol whereas the bottom phase was dominated by dextran. The dextran-rich phase contained more semiconducting species while metallic species was more abundant in the polyethylene glycol rich-phase. It was found via Fourier-Transform Infrared Spectroscopy that cetyltrimethylammonium bromide only present in the dextran-rich phase. A selectivity mechanism is tentatively proposed and discussed.

Coherent polarization locking: an approach to mitigating optical damage in a pulsed Ho:YAG laser.

Intracavity optical damage is mitigated in a pulsed Ho:YAG laser cavity using the coherent polarization locking (CPL) technique. By splitting the available pump power into two individual Ho:YAG laser rods, we passively coherently locked two orthogonal polarization lasers with 9.13 mJ output pulse energies and 14 ns pulsewidths, and operating at 800 Hz repetition rate. A conventional Ho:YAG laser cavity with the same pump and cavity configuration results in severe optical damage when operating at <2 kHz repetition rate, thus limiting the output pulse energies to <5 mJ. We also demonstrated, to the best of our knowledge, the first pulsed operation within the entire CPL Ho:YAG laser cavity by Q-switching in one of the polarization arms, producing nanosecond pulses with no sign of pulse instability.

High energy and average power femtosecond laser for driving mid-infrared optical parametric amplifiers.

We have developed the first (to our knowledge) femtosecond Tm-fiber-laser-pumped Ho:YAG room-temperature chirped pulse amplifier system delivering scalable multimillijoule, multikilohertz pulses with a bandwidth exceeding 12 nm and average power of 15 W. The recompressed 530 fs pulses are suitable for broadband white light generation in transparent solids, which makes the developed source ideal for both pumping and seeding optical parametric amplifiers operating in the mid-IR spectral range.

Fabrication of channeled scaffolds with ordered array of micro-pores through microsphere leaching and indirect Rapid Prototyping technique.

Advanced scaffold fabrication techniques such as Rapid Prototyping (RP) are generally recognized to be advantageous over conventional fabrication methods in terms architectural control and reproducibility. Yet, most RP techniques tend to suffer from resolution limitations which result in scaffolds with uncontrollable, random-size pores and low porosity, albeit having interconnected channels which is characteristically present in most RP scaffolds. With the increasing number of studies demonstrating the profound influences of scaffold pore architecture on cell behavior and overall tissue growth, a scaffold fabrication method with sufficient architectural control becomes imperative. The present study demonstrates the use of RP fabrication techniques to create scaffolds having interconnected channels as well as controllable micro-size pores. Adopted from the concepts of porogen leaching and indirect RP techniques, the proposed fabrication method uses monodisperse microspheres to create an ordered, hexagonal closed packed (HCP) array of micro-pores that surrounds the existing channels of the RP scaffold. The pore structure of the scaffold is shaped using a single sacrificial construct which comprises the microspheres and a dissolvable RP mold that were sintered together. As such, the size of pores as well as the channel configuration of the scaffold can be tailored based on the design of the RP mold and the size of microspheres used. The fabrication method developed in this work can be a promising alternative way of preparing scaffolds with customized pore structures that may be required for specific studies concerning cell-scaffold interactions.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with metastatic colorectal cancer.

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with metastatic colorectal cancer (mCRC), published in late 2022, were adapted in December 2022, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with mCRC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with mCRC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Japanese Society of Medical Oncology (JSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian countries. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with mCRC across the different countries of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling and age and stage at presentation, coupled with a disparity in the drug approvals and reimbursement strategies, between the different countries.

Whole transcriptome analysis of the coral Acropora millepora reveals complex responses to CO2-driven acidification during the initiation of calcification.

The impact of ocean acidification (OA) on coral calcification, a subject of intense current interest, is poorly understood in part because of the presence of symbionts in adult corals. Early life history stages of Acropora spp. provide an opportunity to study the effects of elevated CO(2) on coral calcification without the complication of symbiont metabolism. Therefore, we used the Illumina RNAseq approach to study the effects of acute exposure to elevated CO(2) on gene expression in primary polyps of Acropora millepora, using as reference a novel comprehensive transcriptome assembly developed for this study. Gene ontology analysis of this whole transcriptome data set indicated that CO(2) -driven acidification strongly suppressed metabolism but enhanced extracellular organic matrix synthesis, whereas targeted analyses revealed complex effects on genes implicated in calcification. Unexpectedly, expression of most ion transport proteins was unaffected, while many membrane-associated or secreted carbonic anhydrases were expressed at lower levels. The most dramatic effect of CO(2) -driven acidification, however, was on genes encoding candidate and known components of the skeletal organic matrix that controls CaCO(3) deposition. The skeletal organic matrix effects included elevated expression of adult-type galaxins and some secreted acidic proteins, but down-regulation of other galaxins, secreted acidic proteins, SCRiPs and other coral-specific genes, suggesting specialized roles for the members of these protein families and complex impacts of OA on mineral deposition. This study is the first exhaustive exploration of the transcriptomic response of a scleractinian coral to acidification and provides an unbiased perspective on its effects during the early stages of calcification.

Preserving a diffraction-limited beam in Ho:YAG laser using coherent polarization locking.

We overcome several thermal issues present in Ho:YAG lasers by distributing the gain over a larger volume and achieve a diffraction-limited beam using coherent polarization locking. Increased single-pass absorption, suppression of output power saturation, and improvement in beam quality were shown using the coherent polarization locking technique as compared to a conventional Ho:YAG laser cavity with the same pump and cavity configuration. Ten watts of CW Ho:YAG laser power was generated with >96% coherent combining efficiency.

Esophageal tissue engineering: an in-depth review on scaffold design.

Treatment of esophageal cancer often requires surgical procedures that involve removal. The current approaches to restore esophageal continuity however, are known to have limitations which may not result in full functional recovery. In theory, using a tissue engineered esophagus developed from the patient's own cells to replace the removed esophageal segment can be the ideal method of reconstruction. One of the key elements involved in the tissue engineering process is the scaffold which acts as a template for organization of cells and tissue development. While a number of scaffolds range from traditional non-biodegradable tubing to bioactive decellularized matrix have been proposed to engineer the esophagus in the past decade, results are still not yet favorable with many challenges relating to tissue quality need to be met improvements. The success of new esophageal tissue formation will ultimately depend on the success of the scaffold being able to meet the essential requirements specific to the esophageal tissue. Here, the design of the scaffold and its fabrication approaches are reviewed. In this paper, we review the current state of development in bioengineering the esophagus with particular emphasis on scaffold design.

Bacterial diversity on different surfaces in urban freshwater.

Microbial loads in freshwater systems have important implications in biogeochemical cycling in urban environments. Immersed surfaces in freshwaters provide surfaces for bacterial attachment and growth. Microorganisms that adhere initially to these surfaces play a critical role in biofilm formation and sustenance. Currently, there is little understanding on the type of organisms that initially adhere to different surfaces in urban canals. In this study, water from an urban stormwater canal was employed to allow bacteria to attach to different surfaces in a flowcell apparatus and understand the differences and changes in bacterial community structure. Bacterial communities were highly diverse on different surfaces as indicated by Jaccard's indices of 0.14-0.56. Bacteria on aluminium were the most diverse and on Plexiglas the least. Bacterial communities were highly dynamic in the early attachment phase and it changed by 59% between 3 and 6 h on aluminium. Specificity of attachment to surfaces was observed for some bacteria. Judicious use of materials in urban aquatic environment would help mitigate microbial load in urban waters.

Severe diabetic papillopathy mimicking non-arteritic anterior ischemic optic neuropathy (NAION) in a young patient.

With the pathophysiology not clearly understood and fewer than 130 cases having been reported in the literature, diabetic papillopathy presents a special challenge to the ophthalmologist. We report a case of a young patient with more than 12 years of type 1 diabetes mellitus (T1DM) on insulin with poor compliance to treatment who presented with sudden bilateral loss of vision. Ocular examination, fluorescence angiography (FA) and systemic signs were conclusive of diabetic papillopathy. His fasting blood sugar level was high and serum glycosylated haemoglobin (HbA1c) indicated a long term fluctuating blood glucose control. His vision initially improved with treatment, but later deteriorated with tight glycemic control.

Challenges in diagnosis and management of pseudoptosis secondary to asymmetrical skin creases.

INTRODUCTION: Asymmetrical eyelid skin crease may be mistaken for ptosis due to apparent narrowing of the palpebral fissure in the eye without the skin crease. This study describes a series of patients who were mistakenly referred for ptosis operation as a result of absent skin crease. METHODS: Retrospective case review. RESULTS: A total of 8 patients (5 males and 3 females) were referred by the general ophthalmologists because of suspected ptosis. Although skin creases asymmetry was noted by the general ophthalmologists, the apparent narrowing of the palpebral fissure was thought to be caused by ptosis. However, measurement of the palpebral fissures in both eyes were normal. Creation of a symmetrical skin crease in the affected eye correct the appearent palpebral fissure narrowing. This could be achieved by either surgical or non-surgical means (tape or glue). CONCLUSION: Patients with asymmetrical skin crease of the upper eyelid can give rise to apparent differences in palpebral apertures which may be mistaken for ptosis. The treatment of choice is to create symmetrical skin crease in the eye with absent skin crease to correct the pseudoptosis. Recognition of this condition is important to avoid unnecessary ptosis surgery.

Lurasidone-Induced Manic Switch in an Adolescent with Bipolar I Disorder: a Case Report.

Lurasidone is used for treatment of bipolar depression in adults and adolescents. Lurasidone-associated manic switch has been reported in adults but not yet in adolescents. We report a case of lurasidone-induced manic switch in a male adolescent treated for bipolar I depression. Five days after adding lurasidone to his regimen (sodium valproate and olanzapine), our patient became manic with psychotic features. After discontinuation of lurasidone, he was stabilised with electroconvulsive therapy, and the medication was switched to a lithium-quetiapine combination. This case highlights the potential risk of lurasidone-induced manic switch in adolescents with bipolar depression.

Ocular Perfusion Pressure and Severity of Glaucoma: Is There a Link?

AIM AND OBJECTIVE: To establish the association between 12-month inter-visits ocular perfusion pressure (OPP) and severity of glaucoma. MATERIALS AND METHODS: A total of 164 eyes (60 primary open-angle glaucoma, 52 normal-tension glaucoma, and 52 primary angle-closure glaucoma) of 164 patients were analyzed in this prospective cohort study. Patients who demonstrated good compliance to treatment were recruited. The severity of glaucoma was stratified according to the Advanced Glaucoma Intervention Study (AGIS) score based on reliable and reproducible visual field analysis at baseline. OPP was obtained at baseline and a 3-monthly follow-up visit over a 12-month duration. The pattern and fluctuation of mean OPP were studied. Repetitive measure ANOVA and one-way ANOVA were used for statistical analysis. RESULTS: The inter-visits mean OPP (p = 0.010), systolic OPP (p = 0.020), diastolic OPP (p = 0.010), systolic blood pressure (p = 0.040), and diastolic blood pressure (p = 0.006) showed significant difference with severity of glaucoma. There was no significant difference between mean inter-visits intraocular pressure (IOP) and severity of glaucoma (p = 0.410). The end-stage glaucoma group had the lowest mean OPP and widest inter-visit mean OPP fluctuation. Early and mild glaucoma patients demonstrated higher mean OPP compared with moderate, severe, and end-stage glaucoma. CONCLUSION: There is a significant association between OPP and the severity of glaucoma. Balancing blood pressure and IOP is important in optimizing adequate perfusion and prevent further damage to the optic nerve head. HOW TO CITE THIS ARTICLE: Ch'ng TW, Chua CY, Ummi Kalsom MA, et al. Ocular Perfusion Pressure and Severity of Glaucoma: Is There a Link? J Curr Glaucoma Pract 2021;15(2):78-85.