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.

Cerebral Venous Thrombosis in Patients with COVID-19 Infection: a Case Series and Systematic Review.

BACKGROUND: There has been increasing reports associating the coronavirus disease 2019 (COVID-19) with thromboembolic phenomenon including ischemic strokes and venous thromboembolism. Cerebral venous thrombosis (CVT) is a rare neurovascular emergency that has been observed in some COVID-19 patients, yet much remains to be learnt of its underlying pathophysiology. OBJECTIVE: We present a case series of local patients with concomitant COVID-19 infection and CVT; and aim to perform a systematic review of known cases in the current literature. METHODS: We describe two patients with concomitant COVID-19 infection and CVT from a nationwide registry in Singapore. We then conducted a literature search in PubMed and Embase using a suitable keyword search strategy from 1st December 2019 to 11th June 2020. All studies reporting CVT in COVID-19 patients were included. RESULTS: Nine studies and 14 COVID-19 patients with CVT were studied. The median age was 43 years (IQR=36-58) and majority had no significant past medical conditions (60.0%). The time taken from onset of COVID-19 symptoms to CVT diagnosis was a median of 7 days (IQR=6-14). CVT was commonly seen in the transverse (75.0%) and sigmoid sinus (50.0%); 33.3% had involvement of the deep venous sinus system. A significant proportion of patients had raised D-dimer (75.0%) and CRP levels (50.0%). Two patients reported presence of antiphospholipid antibodies. Most patients received anticoagulation (91.7%) while overall mortality rate was 45.5%. CONCLUSIONS: The high mortality rate of CVT in COVID-19 infection warrants a high index of suspicion from physicians, and early treatment with anticoagulation should be initiated.

Diffusion-weighted MRI abnormalities in an outbreak of Streptococcus agalactiae Serotype III, multilocus sequence type 283 meningitis.

PURPOSE: In 2015, an outbreak of group B streptococcal (GBS) infection caused by Streptococcus agalactiae Serotype III, multilocus sequence type 283, related to consuming infected raw freshwater fish, affected more than 200 patients in Singapore. We describe the clinical, laboratory, and neuroimaging features of a subgroup of adults with central nervous system (CNS) infections caused by GBS. MATERIALS AND METHODS: The database of the Singapore Neurologic Infections Program (SNIP), a national multicenter study for surveillance of infectious neurologic disease, was reviewed to select patients with GBS CNS infection during the outbreak. Cases were diagnosed on the basis of clinical features, cerebrospinal fluid (CSF) findings and identification or isolation of Streptococcus agalactiae in the blood or CSF. Demographic, clinical and neuroradiological information was obtained prospectively and retrospectively abstracted. RESULTS: Fourteen patients (6 male, 8 female; median age, 58 years) presented with fever, meningism, headache, encephalopathy, focal neurological deficits, and/or seizures. All except two were previously healthy. Diffusion-weighted imaging (DWI) on admission was abnormal in 13 patients, showing tiny hyperintensities in the subarachnoid space (7 patients), ventricles (6 patients) and brain parenchyma (8 patients); 5 patients had cerebellar abnormalities. CONCLUSION: Among healthy non-pregnant adults infected with Serotype III, multilocus sequence type 283 GBS meningitis linked to eating infected raw freshwater fish, DWI detected small pus collections and unusual cerebellar involvement. A collaborative national surveillance system that includes MRI can be helpful during unusual food-borne zoonotic infectious disease outbreaks. LEVEL OF EVIDENCE: 4 J. Magn. Reson. Imaging 2017;45:507-514.

National surgical antibiotic prophylaxis guideline in Singapore.

INTRODUCTION: Institutional surgical antibiotic prophylaxis (SAP) guidelines are in place at all public hospitals in Singapore, but variations exist and adherence to guidelines is not tracked consistently. A national point prevalence survey carried out in 2020 showed that about 60% of surgical prophylactic antibiotics were administered for more than 24 hours. This guideline aims to align best practices nationally and provides a framework for audit and surveillance. METHOD: This guideline was developed by the National Antimicrobial Stewardship Expert Panel's National Surgical Antibiotic Prophylaxis Guideline Development Workgroup Panel, which comprises infectious diseases physicians, pharmacists, surgeons and anaesthesiologists. The Workgroup adopted the ADAPTE methodology framework with modifications for the development of the guideline. The recommended duration of antibiotic prophylaxis was graded according to the strength of consolidated evidence based on the scoring system of the Singapore Ministry of Health Clinical Practice Guidelines. RESULTS: This National SAP Guideline provides evidence-based recommendations for the rational use of antibiotic prophylaxis. These include recommended agents, dose, timing and duration for patients undergoing common surgeries based on surgical disciplines. The Workgroup also provides antibiotic recommendations for special patient population groups (such as patients with ß-lactam allergy and patients colonised with methicillin-resistant Staphylococcus aureus), as well as for monitoring and surveillance of SAP. CONCLUSION: This evidence-based National SAP Guideline for hospitals in Singapore aims to align practices and optimise the use of antibiotics for surgical prophylaxis for the prevention of surgical site infections while reducing adverse events from prolonged durations of SAP.

Evaluation of multi-component interventions for prevention of nosocomial pneumonia in older adults: a randomized, controlled trial.

AIMS: To evaluate the efficacy of multi-component interventions for prevention of hospital-acquired pneumonia in older patients hospitalized in geriatric wards. METHODS: A randomized, parallel-group, controlled trial was undertaken in patients aged 65 and above who were admitted to a tertiary hospital geriatric unit from January 1, 2016 to June 30, 2018 for an acute non-respiratory illness. Participants were randomized by to receive either a multi-component intervention (consisting of reverse Trendelenburg position, dysphagia screening, oral care and vaccinations), or usual care. The outcome measures were the proportion of patients who developed hospital-acquired pneumonia during hospitalisation, and mean time from randomization to the next hospitalisation due to respiratory infections in 1 year. RESULTS: A total of 123 participants (median age, 85; 43.1% male) were randomized, (n = 59) to intervention group and (n = 64) to control group. The multi-component interventions did not significantly reduce the incidence of hospital-acquired pneumonia but did increase the mean time to next hospitalisation due to respiratory infection (11.5 months vs. 9.5 months; P = 0.049), and reduced the risk of hospitalisation in 1 year (18.6% vs. 34.4%; P = 0.049). Implementation of multi-component interventions increased diagnoses of oropharyngeal dysphagia (35.6% vs. 20.3%; P < 0.001) and improved the influenza (54.5% vs 17.2%; P < 0.001) and pneumococcal vaccination rates (52.5% vs. 20.3%; P < 0.001). CONCLUSIONS: The nosocomial pneumonia multi-component intervention did not significantly reduce the incidence of hospital-acquired pneumonia during hospitalisation but reduce subsequent hospitalisations for respiratory infections. CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov, NCT04347395.

Disentangling etiologies of CNS infections in Singapore using multiple correspondence analysis and random forest.

Central nervous system (CNS) infections cause substantial morbidity and mortality worldwide, with mounting concern about new and emerging neurologic infections. Stratifying etiologies based on initial clinical and laboratory data would facilitate etiology-based treatment rather than relying on empirical treatment. Here, we report the epidemiology and clinical outcomes of patients with CNS infections from a prospective surveillance study that took place between 2013 and 2016 in Singapore. Using multiple correspondence analysis and random forest, we analyzed the link between clinical presentation, laboratory results, outcome and etiology. Of 199 patients, etiology was identified as infectious in 110 (55.3%, 95%-CI 48.3-62.0), immune-mediated in 10 (5.0%, 95%-CI 2.8-9.0), and unknown in 79 patients (39.7%, 95%-CI 33.2-46.6). The initial presenting clinical features were associated with the prognosis at 2 weeks, while laboratory-related parameters were related to the etiology of CNS disease. The parameters measured were helpful to stratify etiologies in broad categories, but were not able to discriminate completely between all the etiologies. Our results suggest that while prognosis of CNS is clearly related to the initial clinical presentation, pinpointing etiology remains challenging. Bio-computational methods which identify patterns in complex datasets may help to supplement CNS infection diagnostic and prognostic decisions.

Murine typhus presenting with status epilepticus.

Patients with rickettsial infection usually present with a febrile illness, headache, arthromyalgia and various biochemical abnormalities. Neurologic involvement is rare in murine typhus. Here, we report a case of a patient who presented with status epilepticus secondary to Rickettsia typhi infection.

Disseminated Cryptococcosis in a Non-HIV Patient in Singapore.

We present a case of disseminated cryptococcosis (DC) in a 71-year-old gentleman with systemic lupus erythematosus (SLE) on long-term corticosteroids. He initially presented with right arm cellulitis in a tertiary hospital in Singapore and was subsequently diagnosed with DC involving skin, meninges, blood, and possibly pulmonary involvement. He eventually succumbed to the disease despite prolonged antifungal therapy. Through this case, we wish to highlight an atypical clinical presentation of an uncommon infection and hope to share the importance of considering DC in the differential diagnosis of nonresolving cellulitis among immunocompromised individuals. Mortality and morbidity rates for this condition remain high despite appropriate treatment. Early diagnosis and treatment are crucial for improved outcomes. More research is needed to improve the therapeutic modalities for treatment of DC and to improve the clinical outcomes for this life-threatening condition.

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.

Pneumoperitoneum during treatment of abdominal tuberculosis in a Non-HIV patient: Natural progression or paradoxical worsening?

Paradoxical reactions during tuberculosis (TB) treatment are well-described in the HIV seropositive population but less so in the HIV seronegative group. Abdominal TB rarely presents as spontaneous perforation; cases occurring during anti-TB therapy are even rarer. We describe the clinical progress of a case of an HIV-negative patient who developed acute peritonitis while on anti-TB treatment for peritoneal TB through a series of clinical, radiological and histological images. Visceral perforation can occur as a complication of TB treatment. A high index of suspicion with early surgical intervention is crucial in the management of such cases.

Kikuchi-Fujimoto disease presenting after consumption of 'Miracle Mineral Solution' (sodium chlorite).

We present a case report of a 41-year-old woman of Malay ethnicity who presented with an 11-day history of fever and left-sided lymphadenopathy after consuming 'Miracle Mineral Solution' (sodium chlorite solution) for the first time. A diagnosis of Kikuchi-Fujimoto disease was established via lymph node biopsy after other differentials were excluded. The aetiology of Kikuchi-Fujimoto disease remains controversial, but viral, autoimmune and physicochemical causes have been suggested as possibilities. In this case, we hypothesise that oxidative injury from sodium chlorite initiated an inflammatory response, which triggered the onset of Kikuchi-Fujimoto disease.

Oxindole derivatives: synthesis and antiglycation activity.

Oxindole derivatives 3-25 have been synthesized from commercially available oxindole by refluxing with different aromatic aldehydes in good yields. Their in vitro antiglycation potential has been evaluated. They showed a varying degree of antiglycation activity with IC50 values ranging between 150.4 - 856.7 µM. 3-[(3-Chlorophenyl)methylidene]- 1,3-dihydro-2H-indol-2-one (IC50 = 150.4 ± 2.5 µM) is the most active compound among the series, better than the standard rutin with an IC50 value 294.5 ± 1.50 µM. The structures of the compounds were elucidated by 1H-NMR and mass spectroscopy and elemental analysis. A limited structure-activity relationship has been developed.