Low incidence of venous thrombosis but high incidence of arterial thrombotic complications among critically ill COVID-19 patients in Singapore.

BACKGROUND: Arterial and venous thrombosis are reported to be common in critically ill COVID-19 patients. METHOD AND RESULTS: This is a national multicenter retrospective observational study involving all consecutive adult COVID-19 patients who required intensive care units (ICU) admission between 23 January 2020 and 30 April 2020 in Singapore. One hundred eleven patients were included and the venous and arterial thrombotic rates in ICU were 1.8% (n = 2) and 9.9% (n = 11), respectively. Major bleeding rate was 14.8% (n = 16). CONCLUSIONS: Critically ill COVID-19 patients in Singapore have lower venous thromboembolism but higher arterial thrombosis rates and bleeding manifestations than other reported cohorts.

Impact of formulary interventions on the minimum inhibitory concentration of methicillin-resistant Staphylococcus aureus to mupirocin, chlorhexidine, and octenidine in a Singapore tertiary institution.

Methicillin-resistant Staphylococcus aureus (MRSA) decolonization is an effective measure to prevent clinical infection but resistance is a concern. We aim to evaluate the impact of mupirocin (MUP) ointment formulary removal, plateauing use of chlorhexidine gluconate (CHG), and hospital-wide introduction of octenidine (OCT)-based products on the minimum inhibitory concentration (MIC) of MRSA to MUP, CHG, and OCT in our hospital. A prevalence study was conducted at three time points (TP) on consecutive MRSA screening isolates to evaluate for their MICs to MUP, CHG, and OCT using broth microdilution sensititre plates and detection of the ileS-2 gene encoding high-level MUP resistance in 2013 (pre-intervention TP1; n = 160), 2016 (early post-intervention TP2; n = 99) and 2017 (late post-intervention TP3; n = 76). Statistical analyses were performed using Chi square test with reference from TP1. There was a significant improvement in MUP susceptibility (MIC < 4 mcg/ml) from 71.9% (TP1) to 86.9% (TP2; p = 0.006) to 88.2% (TP3; p = 0.007). The prevalence of MUP high-level resistance (MIC > 256 mcg/ml) reduced from 25.0% (TP1) to 12.1% (TP2; p = 0.014) to 5.3% (TP3; p = 0.001). Likewise, the prevalence of isolates harboring the ileS-2 gene decreased from 28.1% (TP1) to 18.2% (TP2; p = 0.072) to 9.2% (TP3; p = 0.002). OCT MIC range remains stable at 0.5 to 1 mcg/ml across all three TPs. The proportion of isolates with reduced CHG susceptibility (MIC ≥ 4 mcg/ml) increased over the three TPs from 23.1 to 27.2% (p = 0.45) to 42.1% (p = 0.003). Active formulary regulations have an impact on the resistance profile of MRSA and can be used as a strategy to preserve the MRSA decolonization armamentarium.

Cryptococcus gattii Infection Presenting as an Aggressive Lung Mass.

Cryptococcus gattii is an endemic fungus predominantly isolated in the tropical and subtropical regions, causing predominantly pulmonary disease with a predilection for the central nervous system. Herein, we report a case of rapidly progressing C. gattii pneumonia in an immune-deficient but virologically suppressed host with underlying human immunodeficiency viral (HIV) infection, exhibiting various fungal morphologies from bronchoalveolar lavage (BAL) cytological specimens. A 51-year-old Chinese male with known HIV disease was admitted to the Singapore General Hospital for evaluation of functional decline, febrile episodes, and a left hilar mass on chest radiograph. Computed tomography (CT) showed consolidation in the apical segment of the left lower lobe. He underwent bronchoscopy and BAL. Positron emission tomography-computed tomography done 10 days after the initial CT showed approximate doubling of the pulmonary lesion. Cytological examination of the fluid revealed yeasts of varying sizes. Subsequent fungal culture from BAL fluid grew C. gattii 10 days later.

Assessment of bridge scour in the lower, middle, and upper Yangtze River estuary with riverbed sonar profiling techniques.

Riverbed scour of bridge piers can cause rapid loss in foundation strength, leading to sudden bridge collapse. This study used multi-beam echo sounders (Seabat 7125) to map riverbed surrounding the foundations of four major bridges in the lower, middle, and upper reaches of the 700-km Yangtze River Estuary (YRE) during June 2015 and September 2016. The high-resolution data were utilized to analyze the morphology of the bridge scour and the deformation of the wide-area riverbed (i.e., 5-18 km long and 1.3-8.3 km wide). In addition, previous bathymetric measurements collected in 1998, 2009, and 2013 were used to determine riverbed erosion and deposition at the bridge reaches. Our study shows that the scour depth surrounding the bridge foundations progressed up to 4.4-19.0 m in the YRE. Over the past 5-15 years, the total channel erosion in some river reaches was up to 15-17 m, possessing a threat to the bridge safety in the YRE. Tide cycles seemed to have resulted in significant variation in the scour morphology in the lower and middle YRE. In the lower YRE, the riverbed morphology displayed one long erosional ditch on both sides of the bridge foundations and a long-strip siltation area distributed upstream and downstream of the bridge foundations; in the middle YRE, the riverbed morphology only showed erosional morphology surrounding the bridge foundations. Large dunes caused deep cuts and steeper contours in the bridge scour. Furthermore, this study demonstrates that the high-resolution grid model formed by point cloud data of multi-beam echo sounders can clearly display the morphology of the bridge scour in terms of wide areas and that the sonar technique is a very useful tool in the assessment of bridge scours.

Spatiotemporal changes of urban heat island effect relative to land surface temperature: a case study of Jinan City, China.

The urban heat island (UHI) effect has become increasingly prevalent and significant with the accelerated pace of urbanization, posing challenges for urban planners and policymakers. To reveal the spatiotemporal variations of the urban heat island effect in Jinan City, this study utilized Landsat satellite images from 2009, 2014, and 2019, employing the classic Mono-Window algorithm to extract land surface temperature (LST). Additionally, Geodetector was introduced to conduct a detailed analysis of the relationship between LST in Jinan City and land cover types (vegetation, water bodies, and buildings). The results indicate a significant increase in the severity of the urban heat island effect in Jinan from 2009 to 2019, with the central urban area consistently exhibiting a high-intensity core heat island. Suburban areas of Jinan show a clear trend of merging their heat island effects with the central urban area. The combined area of strong cool island effect zones and cool island effect zones within water bodies reaches 89.7%, while the combined proportion of heat island and strong heat island effect zones in building areas is 62.2%. Vegetation cover (FVC) exerts the greatest influence among all factors on the intensity level of the urban heat island effect. These findings provide a reliable basis for decision-making related to urban planning and construction in Jinan City.

Contamination and source apportionment of metals in urban road dust (Jinan, China) integrating the enrichment factor, receptor models (FA-NNC and PMF), local Moran's index, Pb isotopes and source-oriented health risk.

Contamination and source identifications of metals in urban road dust are critical for remediation and health protection. Receptor models are commonly used for metal source identification, whereas the results are usually subjective and not verified by other indicators. Here we present and discuss a comprehensive approach to study metal contamination and sources in urban road dust (Jinan) in spring and winter by integrating the enrichment factor (EF), receptor models (positive matrix factorization (PMF) and factor analysis with nonnegative constraints (FA-NNC)), local Moran's index, traffic factors and Pb isotopes. Cadmium, Cr, Cu, Pb, Sb, Sn and Zn were the main contaminants, with mean EFs of 2.0-7.1. The EFs were 1.0-1.6 times higher in winter than in spring but exhibited similar spatial trends. Chromium contamination hotspots occurred in the northern area, with other metal contamination hotspots in the central, southeastern and eastern areas. The FA-NNC results indicated Cr contamination primarily resulting from industrial sources and other metal contamination primarily originating from traffic emissions during the two seasons. Coal burning emissions also contributed to Cd, Pb and Zn contamination in winter. FA-NNC model-identified metal sources were verified via traffic factors, atmospheric monitoring and Pb isotopes. The PMF model failed to differentiate Cr contamination from other detrital metals and the above anthropogenic sources, largely due to the model grouping metals by emphasizing hotspots. Considering the FA-NNC results, industrial and traffic sources accounted for 28.5 % (23.3 %) and 44.7 % (28.4 %), respectively, of the metal concentrations in spring (winter), and coal burning emissions contributed 34.3 % in winter. Industrial emissions primarily contributed to the health risks of metals due to the high Cr loading factor, but traffic emissions dominated metal contamination. Through Monte Carlo simulations, Cr had 4.8 % and 0.4 % possibilities posing noncarcinogenic and 18.8 % and 8.2 % possibilities posing carcinogenic risks for children in spring and winter, respectively.

Cultivated Land Input Behavior of Different Types of Rural Households and Its Impact on Cultivated Land-Use Efficiency: A Case Study of the Yimeng Mountain Area, China.

Analyzing cultivated land input behavior (CLIB) at the scale of rural households links with cultivated land-use efficiency (CLUE), this study examined the Yimeng Mountain area in northern China, supported by field survey data from 737 rural households. This research systematically analyzed the characteristics of CLIB of different types of rural households, measured the CLUE of different types of rural households by using a data envelopment analysis (DEA) model, and explored the influence of CLIB on CLUE based on the Tobit regression model. The results show (1) significant differences in the characteristics of the CLIB of different types of rural households in the Yimeng Mountain area. Among them, the highest land, labor, and capital inputs were I part-time rural households (I PTRH), followed by full-time rural households (FTRH). In contrast, II part-time rural households (II PTRH) and non-agricultural rural households (NARH) had higher levels of non-agricultural employment; however, their input levels gradually declined. (2) The CLUE of the sample rural households was generally low and had considerable potential for improvement. Regarding the types of rural households, as the degree of part-time employment increased, the CLUE showed an inverted U-shaped trend of first increased and then decreased, namely, I PTRH > FTRH > II PTRH > NARH. This finding indicates that appropriate part-time employment could help to promote investment in agricultural production and improve the CLUE. (3) The CLIB of rural households had significant effects on CLUE; the literacy of the agricultural labor force, yield-increasing input per unit area, per capita household income, share of agricultural income, operation scale of cultivated land, effective irrigation rate of cultivated land, and soil and water conservation rate of cultivated land had positive effects on improving CLUE. Even so, there was still significant heterogeneity in the degree of influence of different rural household types. The study concluded with some policy recommendations from the perspective of different rural household types to provide references for optimizing farming inputs and improving CLUE.

Spatial and Temporal Changes of Sand Mining in the Yangtze River Basin since the Establishment of the Three Gorges Dam.

The global demand for sand and gravel is at 50 billion tons per year, far exceeding global resource capacities. It reached 7.6 billion tons in 2021 in the Yangtze River Basin (YRB), China. However, production is severely limited in the YRB. Therefore, the incongruity between the supply and demand of river sand is prominent. Wise management of decreasing sand resources in the YRB has become critical since the Three Gorges Dam became operational in 2003. This study synthesized spatial and temporal changes in sand mining activities and quantities along the Yangtze River and its major tributaries from 2004 to 2020. Results from the study show that the mining amount during the period reached 76.2 million tons annually. At the same time, riverine suspended sediment discharge (SSD) downstream of the Three Gorges Dam decreased largely. SSD reduction leads to riverbed erosion, further limiting the riverine sand and gravel sources for mining. Thus, alternative sand and gravel resources, as well as optimizing supply/demand balance, are necessary for sustainable development. There is an urgent need to assess the relationship between river sand resources and exploitation in the YRB for creating a sand and gravel data management system in order to cope with the increasing incongruity between their supply and demand.

Mesenchymal stromal cells alleviate acute respiratory distress syndrome through the cholinergic anti-inflammatory pathway.

Mesenchymal stromal cells (MSCs) have been considered a promising alternative for treatment of acute respiratory distress syndrome (ARDS). However, there is significant heterogeneity in their therapeutic efficacy, largely owing to the incomplete understanding of the mechanisms underlying the therapeutic activities of MSCs. Here, we hypothesize that the cholinergic anti-inflammatory pathway (CAP), which is recognized as a neuroimmunological pathway, may be involved in the therapeutic mechanisms by which MSCs mitigate ARDS. Using lipopolysaccharide (LPS) and bacterial lung inflammation models, we found that inflammatory cell infiltration and Evans blue leakage were reduced and that the expression levels of choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) in lung tissue were significantly increased 6 hours after MSC infusion. When the vagus nerve was blocked or α7 nicotinic acetylcholine (ACh) receptor (α7nAChR)-knockout mice were used, the therapeutic effects of MSCs were significantly reduced, suggesting that the CAP may play an important role in the effects of MSCs in ARDS treatment. Our results further showed that MSC-derived prostaglandin E2 (PGE2) likely promoted ACh synthesis and release. Additionally, based on the efficacy of nAChR and α7nAChR agonists, we found that lobeline, the nicotinic cholinergic receptor excitation stimulant, may attenuate pulmonary inflammation and alleviate respiratory symptoms of ARDS patients in a clinical study (ChiCTR2100047403). In summary, we reveal a previously unrecognized MSC-mediated mechanism of CAP activation as the means by which MSCs alleviate ARDS-like syndrome, providing insight into the clinical translation of MSCs or CAP-related strategies for the treatment of patients with ARDS.

Early oral stepdown antibiotic therapy versus continuing intravenous therapy for uncomplicated Gram-negative bacteraemia (the INVEST trial): study protocol for a multicentre, randomised controlled, open-label, phase III, non-inferiority trial.

BACKGROUND: The incidence of Gram-negative bacteraemia is rising globally and remains a major cause of morbidity and mortality. The majority of patients with Gram-negative bacteraemia initially receive intravenous (IV) antibiotic therapy. However, it remains unclear whether patients can step down to oral antibiotics after appropriate clinical response has been observed without compromising outcomes. Compared with IV therapy, oral therapy eliminates the risk of catheter-associated adverse events, enhances patient quality of life and reduces healthcare costs. As current management of Gram-negative bacteraemia entails a duration of IV therapy with limited evidence to guide oral conversion, we aim to evaluate the clinical efficacy and economic impact of early stepdown to oral antibiotics. METHODS: This is an international, multicentre, randomised controlled, open-label, phase III, non-inferiority trial. To be eligible, adult participants must be clinically stable / non-critically ill inpatients with uncomplicated Gram-negative bacteraemia. Randomisation to the intervention or standard arms will be performed with 1:1 allocation ratio. Participants randomised to the intervention arm (within 72 h from index blood culture collection) will be immediately switched to an oral fluoroquinolone or trimethoprim-sulfamethoxazole. Participants randomised to the standard arm will continue to receive IV therapy for at least 24 h post-randomisation before clinical re-assessment and decision-making by the treating doctor. The recommended treatment duration is 7 days of active antibiotics (including empiric therapy), although treatment regimen may be longer than 7 days if clinically indicated. Primary outcome is 30-day all-cause mortality, and the key secondary outcome is health economic evaluation, including estimation of total healthcare cost as well as assessment of patient quality of life and number of quality-adjusted life years saved. Assuming a 30-day mortality of 8% in the standard and intervention arms, with 6% non-inferiority margin, the target sample size is 720 participants which provides 80% power with a one-sided 0.025 α-level after adjustment for 5% drop-out. DISCUSSION: A finding of non-inferiority in efficacy of oral fluoroquinolones or trimethoprim-sulfamethoxazole versus IV standard of care antibiotics may hypothetically translate to wider adoption of a more cost-effective treatment strategy with better quality of life outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT05199324 . Registered 20 January 2022.

Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine breakthrough infections: a multicentre cohort study.

OBJECTIVES: Highly effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed but variants of concerns are worrisome, especially B.1.617.2 (Delta) which has rapidly spread across the world. We aim to study if vaccination alters virological and serological kinetics in breakthrough infections. METHODS: We conducted a multicentre retrospective cohort study of patients in Singapore who had received a licensed mRNA vaccine and been admitted to hospital with B.1.617.2 SARS-CoV-2 infection. We compared clinical features, virological and serological kinetics (anti-nucleocapsid, anti-spike and surrogate virus neutralization titres) between fully vaccinated and unvaccinated individuals. RESULTS: Out of 218 individuals with B.1.617.2 infection, 84 received an mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and four received a non-mRNA vaccine. Despite significantly older age in the vaccine breakthrough group, only 2.8% (2/71) developed severe COVID-19 requiring oxygen supplementation compared with 53.1% (69/130) in the unvaccinated group (p < 0.001). Odds of severe COVID-19 following vaccination were significantly lower (adjusted odds ratio 0.07 95% CI 0.015-0.335, p 0.001). PCR cycle threshold values were similar between vaccinated and unvaccinated groups at diagnosis, but viral loads decreased faster in vaccinated individuals. Early, robust boosting of anti-spike protein antibodies was observed in vaccinated patients; however, these titres were significantly lower against B.1.617.2 than the wildtype vaccine strain. DISCUSSION: The mRNA vaccines are highly effective at preventing symptomatic and severe COVID-19 associated with B.1.617.2 infection. Vaccination is associated with faster decline in viral RNA load and a robust serological response. Vaccination remains a key strategy for control of the COVID-19 pandemic.

Mesenchymal Stromal Cells Rapidly Suppress TCR Signaling-Mediated Cytokine Transcription in Activated T Cells Through the ICAM-1/CD43 Interaction.

Cell-cell contact participates in the process of mesenchymal stromal cell (MSC)-mediated T cell modulation and thus contributes to MSC-based therapies for various inflammatory diseases, especially T cell-mediated diseases. However, the mechanisms underlying the adhesion interactions between MSCs and T cells are still poorly understood. In this study, we explored the interaction between MSCs and T cells and found that activated T cells could rapidly adhere to MSCs, leading to significant reduction of TNF-α and IFN-γ mRNA expression. Furthermore, TCR-proximal signaling in activated T cells was also dramatically suppressed in the MSC co-culture, resulting in weakened Ca2+ signaling. MSCs rapidly suppressed TCR signaling and its downstream signaling in a cell-cell contact-dependent manner, partially through the ICAM-1/CD43 adhesion interaction. Blockade of either ICAM-1 on MSCs or CD43 on T cells significantly reversed this rapid suppression of proinflammatory cytokine expression in T cells. Mechanistically, MSC-derived ICAM-1 likely disrupts CD43-mediated TCR microcluster formation to limit T cell activation. Taken together, our results reveal a fast mechanism of activated T cell inhibition by MSCs, which provides new clues to unravel the MSC-mediated immunoregulatory mechanism for aGVHD and other severe acute T cell-related diseases.

Autologous transplantation of thecal stem cells restores ovarian function in nonhuman primates.

Premature ovarian insufficiency (POI) is defined as the loss of ovarian activity under the age of 40. Theca cells (TCs) play a vital role during folliculogenesis and TCs dysfunction participate in the pathogenesis of POI. Therefore, transplantation of thecal stem cells (TSCs), which are capable of self-renewal and differentiation into mature TCs, may provide a new strategy for treating POI. To investigate the feasibility, safety, and efficacy of TSCs transplantation in clinically relevant non-human primate (NHP) models, we isolate TSCs from cynomolgus monkeys, and these cells are confirmed to expand continuously and show potential to differentiate into mature TCs. In addition, engraftment of autologous TSCs into POI monkeys significantly improves hormone levels, rescues the follicle development, promotes the quality of oocytes and boosts oocyte maturation/fertilization rate. Taken together, these results for the first time suggest that autologous TSCs can ameliorate POI symptoms in primate models and shed new light on developing stem cell therapy for POI.

Transplantation of hPSC-derived pericyte-like cells promotes functional recovery in ischemic stroke mice.

Pericytes play essential roles in blood-brain barrier (BBB) integrity and dysfunction or degeneration of pericytes is implicated in a set of neurological disorders although the underlying mechanism remains largely unknown. However, the scarcity of material sources hinders the application of BBB models in vitro for pathophysiological studies. Additionally, whether pericytes can be used to treat neurological disorders remains to be elucidated. Here, we generate pericyte-like cells (PCs) from human pluripotent stem cells (hPSCs) through the intermediate stage of the cranial neural crest (CNC) and reveal that the cranial neural crest-derived pericyte-like cells (hPSC-CNC PCs) express typical pericyte markers including PDGFRß, CD146, NG2, CD13, Caldesmon, and Vimentin, and display distinct contractile properties, vasculogenic potential and endothelial barrier function. More importantly, when transplanted into a murine model of transient middle cerebral artery occlusion (tMCAO) with BBB disruption, hPSC-CNC PCs efficiently promote neurological functional recovery in tMCAO mice by reconstructing the BBB integrity and preventing of neuronal apoptosis. Our results indicate that hPSC-CNC PCs may represent an ideal cell source for the treatment of BBB dysfunction-related disorders and help to model the human BBB in vitro for the study of the pathogenesis of such neurological diseases.

A rare case of CMV pneumonia in HIV-infection.

Cytomegalovirus (CMV) pneumonia is a rare opportunistic infection in the setting of HIV (Human Immunodeficiency Virus)-infection. Establishing accurate diagnosis of CMV pneumonia in HIV-infection can be challenging. Co-infections by multiple opportunistic pathogens are common and a high degree of clinical vigilance to evaluate for multiple infections, including CMV pneumonia, should be maintained. As there can be a degree of overlap in clinical and radiological features amongst different opportunistic infections affecting the lungs, definitive microbiological and cytohistologic evidences are needed. Reliance on microbiological evidence of CMV in respiratory specimens alone for the diagnosis of CMV pneumonia will lead to an over-diagnosis of the condition and unnecessary treatment. In our case report, we describe a 53-year-old man with recently diagnosed HIV-infection who presented with non-resolving pneumonia. A diagnosis of CMV pneumonia was reached through consistent clinical, radiological, microbiological and cytologic investigations. The patient made a full clinical recovery after being started on anti-CMV treatment.

Klebsiella Pneumoniae Visceral Organ Abscesses - Clinical Characteristics.

INTRODUCTION: In recent years, Klebsiella pneumonia (KP) has emerged as the predominant cause of pyogenic liver abscess in Asia. KP - as the causative microorganism in other visceral organ abscesses-is less described. In this study, we seeked to describe the clinical characteristics of KP visceral organ abscesses in our institution and evaluated the prescription practices of physicians with regard to antibiotic therapy. MATERIALS AND METHODS: A retrospective analysis of patients with culture positive (blood or abscess aspirate) KP visceral organ abscesses from May 2014 to April 2016 requiring hospitalisation in Changi General Hospital was conducted. RESULTS: A total of 140 adult patients with KP visceral organ abscesses were identified. The commonest site of involvement was the liver (77.9%), followed by genitourinary tract (20.7%). Diabetic patients were more likely to have liver abscesses, genitourinary abscesses, abscesses in 2 or more organs, genitourinary disease with abscess formation outside of the genitourinary tract, and endovascular infection. Patients with extended spectrum beta-lactamase producing KP, were more likely to have an obstructive lesion related to the site of the abscess. Overall mortality rate was 7.1%. Amongst survivors, the mean total duration of parenteral antimicrobial therapy was 2.5 weeks before switching to oral antimicrobial agents. CONCLUSION: Genitourinary tract is the commonest extra-hepatic site for visceral organ abscess in KP infections. Parenteral to oral switch of antimicrobial agents appears to be a safe and effective treatment option.

Quadruple valve infective endocarditis presenting with suspected Austrian syndrome: a case report and a case series of quadruple valve infective endocarditis.

OBJECTIVES: Austrian syndrome comprises the triad of pneumonia, meningitis, and endocarditis secondary to Streptococcus pneumonia. We present what we believe to be the first reported case of Austrian syndrome with quadruple heart valve involvement and review the literature detailing cases of quadruple valve infective endocarditis. CASE PRESENTATION AND RESULTS: A case is presented of a patient with radiographic evidence of a left lower lobe pneumonia. Sequential transthoracic followed by transesophageal echocardiogram done to evaluate the presence of a cardiac murmur revealed the presence of quadruple valve vegetations. Multiple blood cultures were persistently negative. The patient went on to develop seizures secondary to proven meningitis. Microbiological diagnosis was eventually established through positive Streptococcus pneumoniae antigen (Alere BinaxNOW®) from cerebrospinal fluid, establishing a presumptive clinical diagnosis of Austrian syndrome. A computerized PubMed search for reports of quadruple valve infective endocarditis and their references was collated. A total of 22 patients were found, including our patient. The median age of presentation was 47.5 years. Five patients had a history of intravenous drug abuse, another 5 had underlying congenital heart disease, and 1 had both. Two patients (9.1%) had 2 microorganisms isolated. Staphylococcus aureus and Streptococcus viridans (3 cases, 13.6% each) were the most commonly implicated microorganism. Heart failure was the commonest complication, afflicting 11 patients (50.0%). Ten patients (45.5%) underwent surgery. Overall case fatality rate was 50.0%. Cardiac surgery was of statistical significance in predicting survival (P = 0.009). CONCLUSION: Quadruple valve endocarditis is associated with a high mortality rate, and cardiac surgery may be protective.

Invasive Pneumococcal Disease Associated with Fanconi-Like Syndrome.

Acquired causes of Fanconi syndrome in adults are usually due to drugs, toxins or paraproteinaemias. Infectious causes are rarely described. We report a case of invasive pneumococcal disease in a patient who developed a Fanconi-like syndrome during the course of her illness. This patient presented with multiple electrolyte derangements consisting predominantly of hypokalaemia, hypomagnesaemia and hypophosphataemia during hospitalization for invasive pneumococcal disease with possible Austrian syndrome. Further evaluation revealed significant urinary losses of these electrolytes, uric acid and ß2-microglobulin. Together with evidence of hypouricaemia, this is suggestive of proximal renal tubulopathy, and hence a Fanconi-like syndrome. The patient's clinical condition and biochemical anomalies improved following pneumococcus treatment. LEARNING POINTS: Suspect Fanconi syndrome when there are multiple electrolyte derangements consisting of hypokalaemia, hypomagnesaemia and hypophosphataemia.Recognise the common causes of Fanconi syndrome and appreciate that infections such as legionellosis, leptospirosis and pneumococcal disease can potentially result in Fanconi syndrome.The management of Fanconi syndrome is generally supportive and involves treating the underlying cause.

IgG4-Related Disease of the Thyroid Gland Requiring Emergent Total Thyroidectomy: A Case Report.

IgG4-related disease of the thyroid gland is a recently recognized subtype of thyroiditis, often with rapid progression requiring surgical treatment. It is considered as a spectrum of disease varying from early IgG4-related Hashimoto's thyroiditis (HT) pattern to late fibrosing HT or Riedel's thyroiditis patterns. Here, we report a 47-year-old Malay woman presenting with progressively painless neck swelling over 3 years and subclinical hypothyroidism. Computed tomography (CT) scan revealed diffuse thyroid enlargement (up to 13 cm) with retrosternal extension and without regional lymphadenopathy. Fine needle aspiration of the thyroid showed a limited number of follicular epithelial cell groups with widespread Hurthle cell change and scanty background colloid, but no evidence of lymphocytosis. The cytologic features fell into the category of 'atypia of undetermined significance'. Subsequently, the patient developed hypercapnic respiratory failure secondary to extrinsic upper airway compression by the thyroid mass and underwent emergent total thyroidectomy. Histology of the thyroid showed diffuse dense lymphoplasmacytic infiltrate and fibrosis. Follicular cells exhibited reactive nuclear features and some Hurthle cell change. IgG4+ plasma cells were over 40/high power field while overall IgG4/IgG ratio was above 50%. The overall features suggest the diagnosis of IgG4-related disease of the thyroid gland in the form of IgG4-related HT. Post-surgery, the patient was found to have markedly elevated serum IgG4 concentration but PET/CT did not show significant increased fludeoxyglucose uptake in other areas. Her recovery was complicated by a ventilator-associated pneumonia with empyema, limiting early use of corticosteroids for treatment of IgG4-related disease.

An unusual case of fulminant leptospiral myocarditis: a case report.

BACKGROUND: Fulminant myocarditis secondary to leptospirosis is rare and associated with poor outcomes. CASE SUMMARY: We describe a 60-year-old gentleman with fulminant leptospiral myocarditis and profound cardiogenic shock requiring veno-arterial extracorporeal membrane oxygenator (VA-ECMO) support. He was given high-dose pulse steroids early on post-VA-ECMO implantation and achieved full recovery. To our knowledge, this is the first reported case of leptospiral myocarditis with multiorgan dysfunction successfully managed by VA-ECMO and high-dose pulse steroids. DISCUSSION: This case report highlights the potential benefits of steroids in the management of leptospiral myocarditis which requires further validation. Early aggressive supportive management with ECMO should be considered in patients with fulminant leptospiral myocarditis.