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Background Identifying causative adrenal lesions presents a significant diagnostic burden for physicians and radiologists. We describe the use of radiolabelled metomidate to lateralise primary hyperaldosteronism. Case presentation A 52-year old Chinese man with a 5-year history of hypertension was referred for hypokalemia [K 2.7 mmol/L (3.6 - 5.0)]. He had been on Telmisartan 80 mg and Amlodipine 10 mg daily and blood pressure at home ranged 110-120 / 70-80 mmHg. There was no history of poor oral intake, persistent diarrhea or vomiting, and he was not on any other prescription or alternative medications. There was no significant family history of hypertension or sudden cardiac death. Clinic blood pressure was 140/84 mmHg. There were no features suggestive of Cushing’s syndrome. Repeat biochemical tests confirmed hypokalemia (K 3.1 mmol/L), and associated raised bicarbonate 37.3 mmol/L [19 - 29]. Magnesium and creatinine were normal. Aldosterone-renin Ratio was elevated at 8.1 (serum Aldosterone 611 pmol/L [97.3 - 834.0], active renin 2.7 pg/ml [1.8 – 59.4]). Post-saline infusion, non-suppressible serum aldosterone levels of 1137 pmol/L was demonstrated, consistent with autonomous aldosterone production. A computed tomography of the adrenal revealed a 2.3 cm x 1.9 cm nodule on the left adrenal gland consistent with lipid rich adenoma. Adrenal vein sampling (AVS) under continuous synacthen infusion was performed. Adrenal to peripheral cortisol ratio was ≥10 for either adrenal veins, confirming cannulation of the adrenal veins. Aldosterone-cortisol ratios showed lateralization to the left adrenal gland (lateralization ratio of 10.35). There was contralateral suppression of the right adrenal gland with ratio of 0.41. 11C-Metomidate PET-CT scan demonstrated a maximum standardised uptake value (SUVmax) of 26.8 over the left adrenal nodule, while the SUVmax of the right adrenal gland was 16.2. Ratio of the left to right adrenal gland SUVmax was 1.65 (above the threshold of 1.25); and was concordant with AVS. This confirmed that the patient had a left functional adrenal adenoma responsible for hyperaldosteronism. Our patient underwent a left adrenalectomy, and histology was consistent with adrenal cortical adenoma. Prior to surgery he required 72 mmol/l of potassium supplementation daily to maintain K levels of 3.3 – 4.0 mmol/L. Two weeks post-operatively, he was normokalemic (K 4.9 mmol/L) without potassium supplementation. Serum aldosterone normalized to 159.3 pmol/L (active renin 9.3 pg/ml). Blood pressure is well controlled on amlodipine 5mg daily. Conclusion Targeted molecular imaging such as 11C-Metomidate PET-CT could aid localisation of functional adrenal disease to guide definitive surgical management. In the future, this could obviate the need for invasive and technically complex procedures like AVS.

Background Primary Pituitary Lymphoma (PPL) is a rare differential diagnosis for a sellar / suprasellar lesion. Less than 40 cases have been reported. Case presentation A 75-year old Chinese lady with known subclinical hypothyroidism presented with 3-day history of dull frontal headache, giddiness and diplopia. Incomplete left cranial nerve (CN) III palsy was noted with no other neurological deficit or hemodynamic instability. MRI brain and pituitary showed a T1- and T2 isointense, 2.0 x 1.1 x 1.3 cm enhancing mass arising from the left sellar region, extending to the left sphenoid and cavernous sinuses, displacing the pituitary stalk towards the right, with no optic chiasm compression. There was no imaging evidence of apoplexy. Evaluation of anterior pituitary hormones revealed hypocortisolism (peak cortisol post 1mcg Synacthen 344 nmol/L, ACTH 3.5 ng/L [10 - 60]), subclinical hypothyroidism (free T4 9.6 pmol/L [8.8 - 14.4], TSH 7.19 mU/L [0.65 - 3.70]), normal prolactin 7.4 ug/L [5.0-27.7], mildly elevated IGF-1 193.7 mcg/L [67.0 - 189.0] with normal GH 1.0 ng/ml, and elevated FSH appropriate for menopause. Glucocorticoid replacement was started. Though the clinical presentation was not typical of a pituitary macroadenoma, in view of symptomatic improvement and neurological stability, she was conservatively managed with plans for early repeat imaging outpatient. Patient was readmitted 1 month later for headache and decreased left-sided visual acuity. A complete CN III palsy, and new CN II, IV and VI deficits were noted (orbital apex syndrome). Repeat MRI showed increase in the size of the sellar lesion to 2.6 x 2.1 x 1.3 cm, surrounding the optic nerve and with left cavernous and sphenoid sinus invasion. Again, there was no suggestion of apoplexy. Biopsy of the lesion was performed, and histology was consistent with Diffuse Large B-cell Lymphoma and Grade 3A Follicular Lymphoma with high proliferative index (Ki67 70%). Immunohistochemistry excluded carcinoma, meningioma and pituitary tumor. PET-CT and bone marrow aspirate confirmed the diagnosis of PPL without metastasis. After 3 cycles of chemotherapy (Methotrexate, Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone), significant decrease in the size of the lesion was noted on repeat MRI. Only mild asymmetric soft tissue thickening remained noticeable over the left sella and cavernous sinus. Cranial nerve deficits had since completely resolved. Glucocorticoid replacement was continued in the meantime while awaiting the completion of chemotherapy. Conclusion PPL may present in a similar manner as pituitary apoplexy. Absence of typical imaging characteristics of apoplexy in patients with rapid symptom progression and CN involvement should alert clinicians to consider alternative diagnosis including aggressive neoplastic, inflammatory and infective lesions.

Chikungunya virus (CHIKV) is an alphavirus which causes chronic and incapacitating arthralgia in humans. Although previous studies have shown that antibodies against the virus are produced during and after infection, the fine specificity of the antibody response against CHIKV is not known. Here, using plasma from patients at different times postinfection, we characterized the antibody response against various proteins of the virus. We have shown that the E2 and E3 glycoproteins and the capsid and nsP3 proteins are targets of the anti-CHIKV antibody response. Moreover, we have identified the different regions in these proteins which contain the linear epitopes recognized by the anti-CHIKV antibodies and determined their structural localization. Data also illustrated the effect of a single K 252 Q amino acid change at the E2 glycoprotein that was able to influence antibody binding and interaction between the antibodies and epitope because of the changes of epitope-antibody binding capacity. This study provides important knowledge that will not only aid in the understanding of the immune response to CHIKV infection but also provide new knowledge in the design of modern vaccine development. Furthermore, these pathogen-specific epitopes could be used for future seroepidemiological studies that will unravel the molecular mechanisms of human immunity and protection from CHIKV disease.

To evaluate the effects of a comprehensive dispatcher-assisted CPR (DACPR) training program on bystander CPR (BCPR) rate and the outcomes of out-of-hospital cardiac arrest (OHCA) in Singapore.This is an initial program evaluation of a national DACPR intervention. A before-after analysis was conducted using OHCA cases retrieved from a local registry and DACPR information derived from audio recordings and ambulance notes. The primary outcomes were survival to admission, survival at 30 days post-arrest and good functional recovery.Data was collected before the intervention (April 2010 to December 2011), during the run-in period (January 2012 to June 2012) and after the intervention (July 2012 to February 2013). A total of 2968 cases were included in the study with a mean age of 65.6. Overall survival rate was 3.9% (116) with good functional recovery in 2.2% (66) of the patients. BCPR rate increased from 22.4% to 42.1% (p0.001) with odds ratio (OR) of 2.52 (95% confidence interval [CI]: 2.09-3.04) and ROSC increased significantly from 26.5% to 31.2% (p=0.02) with OR of 1.26 (95%CI: 1.04-1.53) after the intervention. Significantly higher survival at 30 days was observed for patients who received BCPR from a trained person as compared to no BCPR (p=0.001, OR=2.07 [95%CI: 1.41-3.02]) and DACPR (p=0.04, OR=0.30 [95%CI: 0.04-2.18]).A significant increase in BCPR and ROSC was observed after the intervention. There was a trend to suggest improved survival outcomes with the intervention pending further results from the trial.

We aim to study the association between hyperglycemia and in-hospital outcomes among children with moderate and severe traumatic brain injury (TBI). This retrospective cohort study was conducted in a tertiary pediatric hospital between 2003 and 2013. All patients < 16 years old who presented to the Emergency Department within 24 hours of head injury with a Glasgow Coma Scale (GCS) ≤ 13 were included. Our outcomes of interest were death, 14 ventilation-free, 14 pediatric intensive care unit- (PICU-) free, and 28 hospital-free days. Hyperglycemia was defined as glucose > 200 mg/dL (11.1 mmol/L). Among the 44 patients analyzed, the median age was 8.6 years (interquartile range (IQR) 5.0–11.0). Median GCS and pediatric trauma scores were 7 (IQR 4–10) and 4 (IQR 3–6), respectively. Initial hyperglycemia was associated with death (37% in the hyperglycemia group versus 8% in the normoglycemia group,p=0.019), reduced median PICU-free days (6 days versus 11 days,p=0.006), and reduced median ventilation-free days (8 days versus 12 days,p=0.008). This association was however not significant in the stratified analysis of patients with GCS ≤ 8.Conclusion. Our findings demonstrate that early hyperglycemia is associated with increased mortality, prolonged duration of mechanical ventilation, and PICU stay in children with TBI.

Chikungunya virus (CHIKV) and related arboviruses have been responsible for large epidemic outbreaks with serious economic and social impact. The immune mechanisms, which control viral multiplication and dissemination, are not yet known. Here, we studied the antibody response against the CHIKV surface antigens in infected patients. With plasma samples obtained during the early convalescent phase, we showed that the naturally-acquired IgG response is dominated by IgG3 antibodies specific mostly for a single linear epitope ‘E2EP3’. E2EP3 is located at the N-terminus of the E2 glycoprotein and prominently exposed on the viral envelope. E2EP3-specific antibodies are neutralizing and their removal from the plasma reduced the CHIKV-specific antibody titer by up to 80%. Screening of E2EP3 across different patient cohorts and in non-human primates demonstrated the value of this epitope as a good serology detection marker for CHIKV infection already at an early stage. Mice vaccinated by E2EP3 peptides were protected against CHIKV with reduced viremia and joint inflammation, providing a pre-clinical basis for the design of effective vaccine against arthralgia-inducing CHIKV and other alphaviruses.