Combinatorial Hypofractionated Radiotherapy and Pembrolizumab in Anaplastic Thyroid Cancer.

Objectives Anaplastic thyroid cancer (ATC) is an aggressive disease associated with poor outcomes and resistance to therapies. Our study aim was to evaluate the activity of a combinatorial regimen of sandwich sequencing of pembrolizumab immunotherapy and hypofractionated radiotherapy (RT). Methods In this case series, patients with ATC received hypofractionated RT (QUAD-shot) and intravenous pembrolizumab 200mg every 3-4 weeks. Pembrolizumab was continued until disease progression or up till 24 months. Concurrent Lenvatinib treatment was allowed. Primary endpoint was best overall response (BOR) and progression-free survival (PFS). Additionally, we performed immune profiling of circulating T cells in a responder to investigate the immune response to our combinatorial treatment. Results At median follow-up of 32.6 months (IQR: 26.4-38.8), of a cohort of 5 patients, BOR was 80%; with 2 complete responses (CR) and 2 partial responses (PR). Patients who achieved CR remained disease-free at last follow-up. Median PFS was 7.6 months (IQR: 6.2-NR), and 1-year PFS and overall survival rate was 40% (95% CI: 13.7-100) for both. Treatment was well-tolerated, with mostly grade 1-2 adverse events. Immune profiling of one partial responder revealed an increase in activated CD4 and CD8 T cells post-QUAD-shot RT, which was further enhanced during the maintenance phase of pembrolizumab. Conclusions Herein, we reported a case series of 5 patients with ATC, with 2 long-term survivors who were treated with surgical debulking followed by QUAD-shot RT and pembrolizumab, possibly due to synergy of local and systemic treatments in activating anti-tumour immunogenic cytotoxicity. This regimen warrants further investigation in a larger cohort of patients.

Active surveillance testing and decontamination strategies in intensive care units to reduce methicillin-resistant Staphylococcus aureus infections.

BACKGROUND: Active surveillance testing (AST) and decontamination strategies (DS) using a topical methicillin-resistant Staphylococcus aureus (MRSA) cleansing agent was introduced in July 2007 in a medical intensive care unit (MICU) and a surgical ICU (SICU) of a tertiary care hospital to reduce the incidence of MRSA infection. METHODS: Data on ICU admissions between July 1, 2007, and June 30, 2008, was analyzed. All subjects, excluding known MRSA status, had an ICU length of stay (LOS) of more than 24 hours and nasal swabs performed on ICU admission, every 7 days during the ICU stay, and on discharge. MICU and SICU specimens were sent for culture and in-house real-time polymerase chain reaction, respectively. MRSA-colonized (MRSAc) patients were subjected to contact isolation precautions and DS for 5 days or until ICU discharge. Data recorded included demographics, LOS, and antibiotic use. Results were analyzed using SPSS. Control charts were used to determine special cause variation. RESULTS: Of 653 eligible patients admitted to the ICU, 85 (13%) were determined to be MRSAc on ICU admission. A further 15% (52 of 351) were determined to be MRSAc during the ICU stay or at discharge. Thus, AST detected MRSA in at least 137 of the 653 patients (21.0%). In contrast, clinical cultures for MRSA were positive in only 12 patients (1.8%). Compared with noncolonized patients, MRSAc patients at any screening point had a longer pre-ICU LOS (P =.001), received more antibiotics (P = .004), and had a longer ICU LOS (P = .003). Compared with the preintervention period of July 2006 to June 2007, there was no significant reduction in mean MRSA infection incidence rate in both ICUs (3.8 to 3.0 per 1000 patient-days [P = .057] in the SICU and 1.4 to 1.7 per 1000 patient-days in the MICU) following intervention. CONCLUSIONS: In ICUs, AST detected 11 times more MRSA than clinical cultures. The lack of reduction in MRSA infection rates in the ICUs does not negate the roles of AST and DS, but does argue for better study design and outcome measures like MRSA transmission incidence, which perhaps would have demonstrated a true benefit of AST and DS.

Prevalence and genotypes of human noroviruses in tropical urban surface waters and clinical samples in Singapore.

The prevalence and genotypes of norovirus genogroup I (GI) and GII in tropical urban catchment waters and an estuarine bay were studied. A comparative analysis was performed with environmental isolates of noroviruses and concurrently identified clinical isolates in Singapore during gastroenteritis outbreaks between August 2006 to January 2007. Noroviruses in environmental water samples were concentrated by using ultrafiltration techniques and then analyzed by reverse transcription-seminested PCR assay targeting the partial capsid region of noroviruses and DNA sequencing. Among the 60 water samples collected, noroviruses were detected in 43 (71.7%) of these samples. Of these 43 norovirus-positive samples, the coexistence of both GI and GII strains was identified in 23 (53.5%) water samples. The phylogenetic analysis revealed multiple genotypes of noroviruses GI and GII in environmental water samples. GI and GII strains were clustered into seven and nine (including two unclassified) genotypes, respectively. The major norovirus genotypes in environmental water samples were GI/2 and GI/4 and GII/4. Genotyping of the 21 norovirus-positive clinical samples showed that all of the strains belonged to the GII/4 cluster. The environmental and clinical norovirus GII/4 isolates showed high levels of nucleotide sequence identity to each other and to the novel GII/4 variant associated with global epidemics of gastroenteritis during 2006. This study suggests the emergence and circulation of multiple novel norovirus GI and GII genotypes in water environments. Further comprehensive surveillance of water environments for noroviruses and routine clinical reporting is warranted.