Galectin-3: action and clinical utility in chronic kidney disease.

Chronic kidney disease is a significant cause of morbidity and mortality worldwide. In recent years, Galectin-3 has been put forward as a potential biomarker of chronic kidney disease progression. This review aims to assess the clinical utility of Galectin-3 in various pathological processes leading up to chronic kidney disease such as diabetes and lupus nephritis. We conducted a systematic search on PubMed from inception to September 2023, using the search term ("Galectin-3" OR "gal-3") AND ("renal" OR "kidney"). Galectin-3 has been shown to be both pro-fibrotic and protective against renal fibrosis through various mechanisms such as apoptotic body clearance and modulation of the Wnt pathway. Studies have found associations between raised Galectin-3, incidence and progression of chronic kidney disease. In lupus nephritis, Galectin-3 may serve as a biomarker for lupus nephritis activity. Although Galectin-3 inhibits cystogenesis, there is no correlation between total kidney volume and Galectin-3 in polycystic kidney disease. The role of Galectin-3 in staging and prognostication of renal cell carcinoma is yet to be determined. Galectin-3 has potential in predicting chronic kidney disease progression, in combination with other biomarkers. However, more trials are required given that present studies demonstrate conflicting results on the relationship between Galectin-3 and clinical outcomes in chronic kidney disease patients of varying aetiologies.

Measurement of renal congestion and compliance following intravenous fluid administration using shear wave elastography.

Objective: Ultrasound shear wave elastography (SWE) is a novel technique that may provide non-invasive measurements of renal compliance. We aimed to investigate the relationship between intravenous (IV) fluid administration and change in SWE measurements. We hypothesised that following IV fluid administration in healthy volunteers, global kidney stiffness would increase and that this increase in stiffness could be quantified using SWE. Our second hypothesis was that graduated doses of IV fluids would result in a dose-dependent increase in global kidney stiffness measured by SWE. Design: Randomised prospective study. Setting: Intensive Care Unit. Participants: Healthy volunteers aged 18-40 years. Interventions: Participants were randomised to receive 20 ml/kg, 30 ml/kg, or 40 ml/kg of normal saline. The volume of fluid infused was based on the actual body weight recorded. Main outcome measures: We recorded average SWE stiffness (kPa with standard deviation of the mean), median SWE stiffness (kPa), and the interquartile range. Results: Ninety-eight percent of participants (44/45) demonstrated an increase in global kidney stiffness following administration of IV fluids. The average SWE pre fluid administration was 7.572 kPa ± 2.38 versus 14.9 kPa ± 4.81 post fluid administration (p < 0.001). In subgroup analysis, there were significant changes in global kidney stiffness pre and post fluid administration with each volume (ml/kg) of fluid administered. Average percentage change in global kidney stiffness from baseline was compared between the three groups. There was no significant difference when comparing groups 1 and 2 (197.1% increase ± 49.5 vs 216.1% ± 72.0, p » 0.398), groups 2 and 3 (216.1% increase ± 72.0 vs 197.8% ± 59.9, p » 0.455), or groups 1 and 3 (197.1% increase ± 49.5 vs 197.8% ± 59.9, p » 0.972). Conclusions: Fluid administration results in immediately visible and quantifiable changes in global kidney stiffness across all infused volumes of fluid.

Pericapsular nerve group (PENG) block for early pain management of elderly patients with hip fracture: a single-center double-blind randomized controlled trial.

BACKGROUND: The pericapsular nerve group block (PENG) is a novel technique that blocks the articular branches of the hip joint. This study aimed to compare its effectiveness to a sham block in elderly patients with hip fractures. METHOD: A randomized double-blind controlled trial was conducted in elderly patients with intertrochanteric and neck of femur fractures. Patients were randomized to receive either PENG block or a sham block. Postblock, systemic analgesia was titrated using a standardized protocol of acetaminophen, oral morphine or patient-controlled analgesia. The primary outcome was the dynamic pain score (Numerical Rating Scale 0-10) at 30 min postblock. Secondary outcomes included pain scores at multiple other time points and 24-hour opioid consumption. RESULTS: 60 patients were randomized and 57 completed the trial (PENG n=28, control n=29). Patients in PENG group had significantly lower dynamic pain scores at 30 min compared with control group (median (IQR) 3 (0.5-5) vs 5 (3-10), p<0.01). For the secondary outcomes, dynamic pain scores were lower in PENG group at 1 hour (median (IQR) 2 (1-3.25) vs 5 (3-8), p<0.01) and 3 hours postblock (median (IQR) 2 (0-5) vs 5 (2-8), p<0.05). Patients in PENG group had lower 24-hour opioid consumption (median (IQR) oral morphine equivalent dose 10 (0-15) vs 15 (10-30) mg, p<0.05). CONCLUSION: PENG block provided effective analgesia for acute traumatic pain following hip fracture. Further studies are required to validate the superiority of PENG blocks over other regional techniques. TRIAL REGISTRATION NUMBER: NCT04996979.

Serum creatinine to absolute lymphocyte count ratio effectively risk stratifies patients who require intensive care in hospitalized patients with coronavirus disease 2019.

Patients with preexisting kidney disease or acute kidney injury had poorer outcomes in coronavirus disease 2019 (COVID-19) illness. Lymphopenia was associated with more severe illness. Risk stratification with simple laboratory tests may help appropriate site patients in a cost-effective manner and ease the burden on healthcare systems. We examined a ratio of serum creatinine level to absolute lymphocyte count at presentation (creatinine-lymphocyte ratio, CLR) in predicting outcomes in hospitalized patients with COVID-19. We analyzed 553 consecutive polymerase chain reaction-positive SARS-COV-2 hospitalized patients. Patients with end-stage kidney disease were excluded. Serum creatinine and full blood count (FBC) examination were obtained within the first day of admission. We examined the utility of CLR in predicting adverse clinical outcomes (requiring intensive care, mechanical ventilation, acute kidney injury requiring renal replacement therapy or death). An optimized cutoff of CLR > 77 was derived for predicting adverse outcomes (72.2% sensitivity, and 83.9% specificity). Ninety-seven patients (17.5%) fell within this cut off. These patients were older and more likely to have chronic medical conditions. A higher proportion of these patients had adverse outcomes (13.4% vs 1.1%, P < .001). On receiver operating curve analyses, CLR predicted patients who had adverse outcomes well (area under curve [AUC] = 0.82, 95%CI 0.72-0.92), which was comparable to other laboratory tests like serum ferritin, C-reactive protein and lactate dehydrogenase. Elevated CLR on admission, which may be determined by relatively simple laboratory tests, was able to reasonably discriminate patients who had experienced adverse outcomes during their hospital stay. This may be a simple and cost-effective means of risk stratification and triage.

Molecular diversity and assemblages of coral symbionts (Symbiodiniaceae) in diverse scleractinian coral species.

The scleractinian coral-associated symbiotic algae Symbiodiniaceae plays an important role in bleaching tolerance and coral resilience. In this study, coral-associated Symbiodiniaceae communities of 14 reef sites of Perhentian and Redang Islands Marine Parks (Malaysia, South China Sea) were characterized using the high-throughput next-generation amplicon sequencing on the ITS2 rDNA marker to inventory the Symbiodiniaceae diversity from a healthy tropical reef system and to generate a baseline for future studies. A total of 64 coral-Symbiodiniaceae associations were characterized in 18 genera (10 families) of scleractinian corals using the SymPortal analytical framework. The results revealed the predominance of Symbiodiniaceae genera Cladocopium (average 82%) and Durusdinium (18%), while Symbiodinium, Breviolum, Fugacium, and Gerakladium were found as minor groups (<0.01%). Of the 39 Cladocopium and Durusdinium major ITS2 sequences, 14 were considered dominant/sub-dominant, with C3u as the predominant type (63.3%), followed by D1 (15%), C27 (10.1%), and C15 (6.9%). A total of 19 and 13 Cladocopium and Durusdinium ITS2-type profiles were detected across the coral species, respectively. Symbiodiniaceae diversity and richness recorded in this study were higher when compared to other reefs in the proximity. With the increasing coral-Symbiodiniaceae associations archived, the database would provide a baseline to assess the changes of Symbiodiniaceae communities in the coral hosts and to explore the potential adaptive roles of this coral-algal association.

Haematological profile of COVID-19 patients from a centre in Singapore.

BACKGROUND: Haematological markers such as absolute lymphopenia have been associated with severe COVID-19 infection. However, in the literature to date, the cohorts described have typically included patients who were moderate to severely unwell with pneumonia and who required intensive care stay. It is uncertain if these markers apply to a population with less severe illness. We sought to describe the haematological profile of patients with mild disease with COVID-19 admitted to a single centre in Singapore. METHODS: We examined 554 consecutive PCR positive SARS-COV-2 patients admitted to a single tertiary healthcare institution from Feb 2020 to April 2020. In all patients a full blood count was obtained within 24 h of presentation. RESULTS: Patients with pneumonia had higher neutrophil percentages (66.5 ± 11.6 vs 55.2 ± 12.6%, p < 0.001), lower absolute lymphocyte count (1.5 ± 1.1 vs 1.9 ± 2.1 x109/L, p < 0.011) and absolute eosinophil count (0.2 ± 0.9 vs 0.7 ± 1.8 × 109/L, p = 0.002). Platelet counts (210 ± 56 vs 230 ± 61, p = 0.020) were slightly lower in the group with pneumonia. We did not demonstrate significant differences in the neutrophil-lymphocyte ratio, monocyte-lymphocyte ratio and platelet-lymphocyte ratio in patients with or without pneumonia. Sixty-eight patients (12.3%) had peripheral eosinophilia. This was more common in migrant workers living in dormitories. CONCLUSION: Neutrophilia and lymphopenia were found to be markers associated with severe COVID-19 illness. We did not find that combined haematological parameters: neutrophil-lymphocyte ratio, monocyte-lymphocyte ratio and platelet-lymphocyte ratio, had any association with disease severity in our cohort of patients with mild-moderate disease. Migrant workers living in dormitories had eosinophilia which may reflect concurrent chronic parasitic infection.

Utility of conventional clinical risk scores in a low-risk COVID-19 cohort.

BACKGROUND: Several specific risk scores for Coronavirus disease 2019 (COVID-19) involving clinical and biochemical parameters have been developed from higher-risk patients, in addition to validating well-established pneumonia risk scores. We compared multiple risk scores in predicting more severe disease in a cohort of young patients with few comorbid illnesses. Accurately predicting the progression of COVID-19 may guide triage and therapy. METHODS: We retrospectively examined 554 hospitalised COVID-19 patients in Singapore. The CURB-65 score, Pneumonia Severity Index (PSI), ISARIC 4C prognostic score (4C), CHA2DS2-VASc score, COVID-GRAM Critical Illness risk score (COVID-GRAM), Veterans Health Administration COVID-19 index for COVID-19 Mortality (VACO), and the "rule-of-6" score were compared for three performance characteristics: the need for supplemental oxygen, intensive care admission and mechanical ventilation. RESULTS: A majority of patients were young (≤ 40 years, n = 372, 67.1%). 57 (10.3%) developed pneumonia, with 16 (2.9% of study population) requiring supplemental oxygen. 19 patients (3.4%) required intensive care and 2 patients (0.5%) died. The clinical risk scores predicted patients who required supplemental oxygenation and intensive care well. Adding the presence of fever to the CHA2DS2-VASc score and 4C score improved the ability to predict patients who required supplemental oxygen (c-statistic 0.81, 95% CI 0.68-0.94; and 0.84, 95% CI 0.75-0.94 respectively). CONCLUSION: Simple scores including well established pneumonia risk scores can help predict progression of COVID-19. Adding the presence of fever as a parameter to the CHA2DS2-VASc or the 4C score improved the performance of these scores in a young population with few comorbidities.

Identification of Fish Species and Toxins Implicated in a Snapper Food Poisoning Event in Sabah, Malaysia, 2017.

In the coastal countries of Southeast Asia, fish is a staple diet and certain fish species are food delicacies to local populations or commercially important to individual communities. Although there have been several suspected cases of ciguatera fish poisoning (CFP) in Southeast Asian countries, few have been confirmed by ciguatoxins identification, resulting in limited information for the correct diagnosis of this food-borne disease. In the present study, ciguatoxin-1B (CTX-1B) in red snapper (Lutjanus bohar) implicated in a CFP case in Sabah, Malaysia, in December 2017 was determined by single-quadrupole selected ion monitoring (SIM) liquid chromatography/mass spectrometry (LC/MS). Continuous consumption of the toxic fish likely resulted in CFP, even when the toxin concentration in the fish consumed was low. The identification of the fish species was performed using the molecular characterization of the mitochondrial cytochrome c oxidase subunit I gene marker, with a phylogenetic analysis of the genus Lutjanus. This is the first report identifying the causative toxin in fish-implicated CFP in Malaysia.

Diverse harmful microalgal community assemblages in the Johor Strait and the environmental effects on its community dynamics.

Coastal ecosystems are often subjected to anthropogenic disturbances that lead to water quality deterioration and an increase in harmful algal bloom (HAB) events. Using the next-generation molecular tool of 18S rDNA metabarcoding, we examined the community assemblages of HAB species in the Johor Strait, Malaysia between May 2018 and September 2019, covering 19 stations across the strait. The molecular operational taxonomic units (OTUs) of HAB taxa retrieved from the dataset (n = 194) revealed a much higher number of HAB taxa (26 OTUs) than before, with 12 taxa belong to new records in the strait. As revealed in the findings of this study, the diversity and community structure of HAB taxa varied significantly over time and space. The most common and abundant HAB taxa in the strait (frequency of occurrence >70%) comprised Heterosigma akashiwo, Fibrocapsa japonica, Pseudo-nitzschia pungens, Dinophysis spp., Gymnodinium catenatum, Alexandrium leei, and A. tamiyavanichii. Also, our results demonstrated that the HAB community assemblages in the strait were dependent on the interplay of environmental variables that influence by the monsoonal effects. Different HAB taxa, constitute various functional types, occupied and prevailed in different environmental niches across space and time, leading to diverse community assemblages and population density. This study adds to the current understandings of HAB dynamics and provides a robust overview of temporal-spatial changes in HAB community assemblages along the environmental gradients in a tropical eutrophic coastal ecosystem.

Elevated liver enzymes in hospitalized patients with COVID-19 in Singapore.

ABSTRACT: Liver dysfunction in patients with COVID-19 (coronavirus disease 2019) has been described. However, it is not clear if the presence of abnormal liver function tests at presentation was related to underlying undiagnosed liver disease, or a result of the viral infection.We retrospectively examined the first 554 consecutive polymerase chain reaction positive SARS-CoV-2 patients admitted from February 2020 to April 2020 to our academic medical centre. We reviewed their clinical data, chest radiography and laboratory studies obtained within 24 hour of admission.Despite similar hemodynamic parameters, we found significant aspartate transaminase elevation (64 ±â€Š141 vs 35 ±â€Š23 U/L, P < .001) in those with pneumonia compared to those without. Elevated liver enzymes were seen in 102 patients (18.4%). They presented with higher temperatures (38.5 ±â€Š0.9 vs 37.5 ±â€Š0.8 degC, P = .011), higher total white cell counts (6.95 ±â€Š2.29 vs 6.39 ±â€Š2.19 x109/L, P = .021), serum ferritin (240 ±â€Š274 vs 165 ±â€Š198 ng/ml, P = .002) and lactate dehydrogenase (632 ±â€Š912 vs 389 ±â€Š107 U/L, P < .001). These patients were more likely to require intensive care (6.9% vs 2.7% P = .036) and mechanical ventilation (5.9% vs 2.2%, P = .046). Migrant workers from dormitories had a higher rate of baseline liver function test abnormalities (88/425 vs 14/129, P = .01), which were more likely to persist at the time of discharge.Despite relatively mild COVID-19 disease, there was a significant prevalence of liver dysfunction, particularly amongst migrant workers. Elevated liver enzymes were associated with more severe disease, despite similar haemodynamic characteristics. Future studies should explore whether pre-existing liver disease may predispose to more severe COVID-19 disease.

Superconducting Quantum Interference in Twisted van der Waals Heterostructures.

We demonstrate the formation of both Josephson junctions and superconducting quantum interference devices (SQUIDs) using a dry transfer technique to stack and deterministically misalign mechanically exfoliated flakes of NbSe2. The current-voltage characteristics of the resulting twisted NbSe2-NbSe2 junctions are found to be sensitive to the misalignment angle of the crystallographic axes, opening up a new control parameter for optimization of the device performance, which is not available in thin-film-deposited junctions. A single lithographic process has then been implemented to shape Josephson junctions into SQUID geometries with typical loop areas of ∼25 µm2 and weak links ∼600 nm wide. At T = 3.75 K in an applied magnetic field, these devices display large stable current and voltage modulation depths of up to ΔIc ∼ 75% and ΔV ∼ 1.4 mV, respectively.

COVID-19 associated parotitis.

While Coronavirus 2019 (COVID-19) typically presents with respiratory tract symptoms, atypical manifestations have been reported. We present a case of a 46-year-old man who presented with fever but no respiratory tract symptoms, and later develops bilateral parotitis. We review the literature for all other reported cases of parotitis and describe common features of these cases. It is important to consider COVID-19 in cases of parotitis, as this impacts patient management and ensures important infection control measures are undertaken.

Hemisensory syndrome: Hyperacute symptom onset and age differentiates ischemic stroke from other aetiologies.

BACKGROUND: An important cause of hemisensory syndrome is ischemic stroke. However, the diagnostic yield of neuroradiological imaging on hemisensory syndrome is low. Therefore, we aim to describe patients hospitalized with isolated hemisensory syndrome, and to identify clinical features associated with an aetiology of ischemic stroke. METHODS: We performed a single centre retrospective observation study, identifying patients who were hospitalised with hemisensory syndrome from October 2015 to March 2016, and whom underwent a magnetic resonance imaging (MRI) brain during the admission. Ischemic stroke was defined as the presence of restricted diffusion-weighted image on the MRI brain. Clinical information was analysed and compared between patients with and without stroke seen on MRI brain. RESULTS: 79 patients, 36 (45.6%) males and 43 (54.4%) females, aged between 30 to 87 years (mean 54), were included in the final analysis. 18 (22.8%) patients were identified to have an acute ischemic stroke. Clinical features associated with ischemic stroke in hospitalised patients with hemisensory syndrome include symptom onset of ≤24 h at presentation (odds ratio 31.4, 95% CI 3.89-254.4), advanced age (odds ratio 1.14, CI 1.05-1.25) and smoking (odds ratio 7.35, 95% CI 1.20-45). CONCLUSION: Older patients, with a history of smoking, and who present with an acute onset of symptoms, are more likely to have ischemic stroke as the cause of their hemisensory syndrome.

Neck swelling and airway narrowing as an initial manifestation of giant cell arteritis.

Giant cell arteritis can result in a wide range of symptoms due to the extensive distribution of the external carotid artery. Face and neck swelling and trismus are under-recognised features of giant cell arteritis and can present as the initial symptom prior to the development of classical temporal tenderness and jaw claudication. The lack of awareness of the less common symptoms may result in a late diagnosis of giant cell arteritis, leading to irreversible vision loss. In this paper, we present a case of neck swelling and airway narrowing as the initial manifestation of giant cell arteritis.

Design and Multicenter Clinical Validation of a 3-Dimensionally Printed Nasopharyngeal Swab for SARS-CoV-2 Testing.

Importance: Three-dimensionally printed nasopharyngeal swabs (3DP swabs) have been used to mitigate swab shortages during the coronavirus disease 2019 (COVID-19) pandemic. Clinical validation for diagnostic accuracy and consistency, as well as patient acceptability, is crucial to evaluate the swab's performance. Objective: To determine the accuracy and acceptability of the 3DP swab for identifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Design, Setting, and Participants: A diagnostic study was conducted from May to July 2020 at 2 tertiary care centers in Singapore with different reference swabs (FLOQSwab [COPAN Diagnostics] or Dacron swab [Deltalab]) and swab processing techniques (wet or dry) to evaluate the performance of the 3DP swab compared with traditional, standard-of-care nasopharyngeal swabs used in health care institutions. The participants were patients with COVID-19 in the first 2 weeks of illness and controls with acute respiratory illness with negative test results for SARS-CoV-2. Paired nasopharyngeal swabs were obtained from the same nostril and tested for SARS-CoV-2 by reverse-transcriptase polymerase chain reaction. The sequence of swabs was randomized based on odd and even participant numbers. Main Outcomes and Measures: Primary outcome measures were overall agreement (OA), positive percentage agreement (PPA), and negative percentage agreement of the 3DP swab compared with reference swabs. Secondary outcome measures were the correlation of cycle threshold (Ct) values of both swabs. Results: The mean (SD) age of participants was 45.4 (13.1) years, and most participants were men (87 of 89 [97.8%]), in keeping with the epidemiology of the COVID-19 pandemic in Singapore. A total of 79 patients with COVID-19 and 10 controls were recruited. Among the patients with COVID-19, the overall agreement and PPA of the 3DP swab was 91.1% and 93.5%, respectively, compared with reference swabs. The PPA was 100% for patients with COVID-19 who were tested within the first week of illness. All controls tested negative. The reverse-transcriptase polymerase chain reaction Ct values for the ORF1ab and E-gene targets showed a strong correlation (intraclass correlations coefficient, 0.869-0.920) between the 3DP and reference swab on independent testing at each institution despite differences in sample processing. Discordant results for both gene targets were observed only at high Ct values. Conclusions and Relevance: In this diagnostic study of 79 patients with COVID-19 and 10 controls, the 3DP swab performed accurately and consistently across health care institutions and could help mitigate strained resources in the escalating COVID-19 pandemic.

Clinical Diagnostic Study of a Novel Injection Molded Swab for SARS-Cov-2 Testing.

INTRODUCTION: The gold standard for COVID-19 diagnosis is currently a real-time reverse transcriptase polymerase chain reaction (RT-PCR) to detect SARS-CoV-2. This is most commonly performed on respiratory secretions obtained via a nasopharyngeal swab. Due to supply chain limitations and high demand worldwide because of the COVID-19 pandemic, access to commercial nasopharyngeal swabs has not been assured. 3D printing methods have been used to meet the shortfall. For longer-term considerations, 3D printing may not compare well with injection molding as a production method due to the challenging scalability and greater production costs of 3D printing. METHODS: To secure sufficient nasopharyngeal swab availability for our national healthcare system, we designed a novel injection molded nasopharyngeal swab (the IM2 swab). We performed a clinical diagnostic study comparing the IM2 swab to the Copan FLOQSwab. Forty patients with a known diagnosis of COVID-19 and 10 healthy controls were recruited. Paired nasopharyngeal swabs were obtained from the same nostril of each participant and tested for SARS-CoV-2 by RT-PCR. RESULTS: When compared to the Copan FLOQswab, results from the IM2 swab displayed excellent overall agreement and positive percent agreement of 96.0% and 94.9%, respectively. There was no significant difference in mean RT-PCR cycle threshold values for the ORF1ab (28.05 vs. 28.03, p = 0.97) and E-gene (29.72 vs. 29.37, p = 0.64) targets, respectively. We did not observe any significant adverse events and there was no significant difference in patient-reported pain. CONCLUSION: In summary, the IM2 nasopharyngeal swab is a clinically safe, highly accurate option to commercial nasopharyngeal swabs.

Demographic shift in COVID-19 patients in Singapore from an aged, at-risk population to young migrant workers with reduced risk of severe disease.

OBJECTIVES: The vast majority of COVID-19 cases in Singapore have occurred amongst migrant workers. This paper examined trends in the hospitalised cases and tested the assumption that the low severity of disease was related to the relatively young affected population. METHODS: All patients with PCR-positive SARS-CoV-2 admitted from February to April 2020 were divided into: (i) imported cases, (ii) locally-transmitted cases outside migrant worker dormitories and (iii) migrant worker dormitory cases. They were examined for underlying comorbidities, clinical progress and outcomes. RESULTS: Imported cases (n = 29) peaked in mid-March 2020, followed by local cases (n = 100) in mid-April 2020; migrant worker cases (n = 425) continued to increase in late April 2020. Migrant worker cases were younger, had few medical comorbidities and less severe disease. As the migrant worker cases increased, the proportion of patients with pneumonia decreased, whilst patients presenting earlier in their illness and asymptomatic disease became more common. CONCLUSION: Singapore experienced a substantial shift in the population at risk of severe COVID-19. Successful control in the community protected an aging population. Large migrant worker dormitory outbreaks occurred, but the disease incurred was less severe, resulting in Singapore having one of the lowest case fatality rates in the world.