Purpose: Clinical responses with programmed death (PD-1) receptor directed antibodies occur in about 20% of patients with advanced head and neck squamous cell cancer (HNSCCa). Viral neoantigens, such as the E6/E7 proteins of HPV16/18 are attractive targets for therapeutic immunization, and offer an immune activation strategy that may be complementary to PD-1 inhibition. Experimental Design: We report Phase Ib/II safety, tolerability and immunogenicity results of immunotherapy with MEDI0457 (DNA immunotherapy targeting HPV16/18 E6/E7 with IL-12 encoding plasmids) delivered by electroporation with CELLECTRA® constant current device. Twenty-two patients with locally advanced, p16+ HNSCCa received MEDI0457. Results: MEDI0457 was associated with mild injection site reactions but no treatment related grade 3–5 adverse events (AEs). Eighteen of 21 evaluable patients showed elevated antigen specific T cell activity by IFNγ ELISpot and persistent cellular responses surpassing 100 SFU/106 PBMC were noted out to one year. Induction of HPV-specific CD8+ T cells was observed. MEDI0457 shifted the CD8+/FoxP3+ ratio in 4/5 post-immunotherapy tumor samples and increased the number of perforin+ immune infiltrates in all five patients. One patient developed metastatic disease and was treated with anti-PD-1 therapy with a rapid and durable complete response. Flow cytometric analyses revealed induction of HPV16 specific PD-1+ CD8+ T cells that were not found prior to MEDI0547 (0% vs. 1.8%). Conclusions: These data demonstrate that MEDI0457 can generate durable HPV16/18 antigen-specific peripheral and tumor immune responses. This approach may be used as a complementary strategy to PD-1/PD-L1 inhibition in HPV-associated HNSCCa to improve therapeutic outcomes.

ObjectivesPregnancy-associated venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), is associated with increased risk of maternal mortality and morbidity. This study aimed to assess potential risk factors for pregnancy-associated VTE.MethodsIn this case-control study, women with pregnancy-associated VTE were identified via International Classification of Diseases codes and included if they had been objectively diagnosed with VTE during pregnancy or within six weeks postpartum, from 2004 to 2016, at KK Women’s and Children’s Hospital or Singapore General Hospital in Singapore. Controls, i.e. pregnant women without VTE, were selected from a prospective longitudinal study. The odds ratio (OR) for VTE was computed for a range of maternal and obstetric factors.Results and conclusionsFrom 2004 to 2016, 89 cases of pregnancy-associated VTE and 926 controls were identifed and analysed using logistic regression. The most significant risk factors for pregnancy-associated VTE were smoking (OR 5.44, p=0.0002) and preterm delivery (OR 5.06, p=0.023). Malay race, multiparity, non-O blood group and caesarean section, were also identified to be of higher risk. These risk factors should be useful in the development of thromboprophylaxis strategies for pregnancy and the postpartum period, especially in Singapore.

ObjectiveTo determine the cumulative incidence, time of occurrence and risk factors of pregnancy‐associated pulmonary embolism (PE) in Singapore, and to review the maternal mortality ratio of PE over the last four decades.Study design and settingIn this retrospective epidemiology review, women with pregnancy‐associated PE were identified via International Classification of Diseases codes and included if they had been objectively diagnosed on imaging with PE during pregnancy or within 6 weeks postpartum from 2004 to 2016 at KK Women's and Children's Hospital (KKH) and Singapore General Hospital (SGH) in Singapore. The medical records were reviewed and the time of occurrence of confirmed PE cases and risk factors for PE were noted.ResultsThere were 18 PE cases out of 174 708 deliveries, of which two were fatal, giving a cumulative incidence of PE at 1.03 per 10 000 deliveries and a mortality rate of 11.1%. The maternal mortality ratio is 1.14 per 100 000 deliveries, the lowest compared to that of the previous three decades (2.5–4.9 per 100 000 deliveries). Majority of PE (66.7%) occurred during the first 2 weeks postpartum. Cumulative incidence of postpartum PE was four times more in caesarean section compared to vaginal delivery at 1.58 per 10 000 deliveries and 0.40 per 10 000 deliveries, respectively.ConclusionAlthough the cumulative incidence of pregnancy‐associated PE in Singapore is low, it is comparable to the United Kingdom (UK) and United States (US). Risk assessment and thromboprophylaxis have decreased PE mortality significantly during this period.

Summary We report a case of subacute thyroiditis in a 40-year-old female who initially presented with painful thyroid nodules without clinical and biochemical evidence of hyperthyroidism. Thyroid ultrasound was done to evaluate the thyroid nodules and fine-needle aspiration (FNA) was performed in view of the suspicious features. As the FNA showed a follicular lesion of undetermined significance or atypia of undetermined significance (FLUS/AUS, Bethesda III), she was advised for surgical excision. She was subsequently diagnosed with subacute thyroiditis based on her clinical symptoms, biochemical evidence of hyperthyroidism, raised erythrocyte sedimentation rate (ESR) as well as low uptake on thyroid scintigraphy. The thyroid lesions disappeared after symptomatic treatment. It is important to recognise that subacute thyroiditis can present with painful thyroid lesions with ultrasound features similar to suspicious thyroid nodules which can resolve with the resolution of the thyroiditis. Learning points Subacute thyroiditis can present with atypical features such as the absence of pain, normal erythrocyte sedimentation rate or absence of hyperthyroidism. In subacute thyroiditis, ultrasound findings are commonly described as focal or multifocal lesions with poorly defined and heterogeneous and hypoechoic echogenicity which can be misdiagnosed as malignancy. Thyroid lesions can resolve with the resolution of thyroiditis with or without symptomatic treatment.

Introduction: Dengue is a mosquito-borne viral infection endemic in Singapore. Its impact in renal transplantation is limited to small case series. We aimed to characterise the clinical presentation and outcomes of dengue infection among renal transplant recipients in Singapore. Methods: We conducted a 15-year retrospective review of dengue in renal transplant patients treated at Singapore General Hospital between January 2005 and October 2019. The diagnosis of dengue was made if there were a compatible clinical syndrome and a positive dengue diagnostic assay (Dengue NS1 antigen, IgM or RT-PCR). Results: 31 patients were diagnosed with dengue, 18 (58.1%) were deceased donor recipients. The median age was 52 (IQR 40–61) years; 16 (51.6%) were females. The median time to diagnosis was 99 (IQR 18–169) months from transplant. The most common clinical symptoms were fever (87.1%), myalgia (41.9%), gastrointestinal symptoms (38.7%) and headache (25.8%). 19 (61.3%) patients had dengue without warning signs, 9 (29.0%) had dengue with warning signs, 3 (9.7%) had severe dengue and 30 (96.8%) were hospitalized. 17 (54.8%) patients had graft dysfunction, 16 (94.1%) of whom had recovery of graft function. 1 (3.2%) patient required dialysis and subsequently died. There were two cases of donor-derived infections (DDIs) with favourable outcomes. Conclusion: Our experience with dengue in renal transplant recipients is concordant with published data. Although graft dysfunction is common, it is often transient with favourable outcomes. Outpatient management may be considered for mild infections. Although dengue DDIs are uncommon, more stringent donor screening may be considered in endemic regions.