Protection from infection and reinfection due to the Omicron BA.1 variant in care homes.

Introduction: Following the emergence of SARS-CoV-2 in 2020, care homes were disproportionately impacted by high mortality and morbidity of vulnerable elderly residents. Non-pharmaceutical interventions (NPIs) and improved infection control measures together with vaccination campaigns have since improved outcomes of infection. We studied the utility of past infection status, recent vaccination and anti-S antibody titres as possible correlates of protection against a newly emergent Omicron variant infection. Methods: Prospective longitudinal surveillance of nine sentinel London care homes from April 2020 onwards found that all experienced COVID-19 outbreaks due to Omicron (BA.1) during December 2021 and January 2022, despite extensive prior SARS-CoV-2 exposure and high COVID-19 vaccination rates, including booster vaccines (>70% residents, >40% staff). Results: Detailed investigation showed that 46% (133/288) of Omicron BA.1 infections were SARS-CoV-2 reinfections. Two and three COVID-19 vaccine doses were protective against Omicron infection within 2-9 weeks of vaccination, though protection waned from 10 weeks post-vaccination. Prior infection provided additional protection in vaccinated individuals, approximately halving the risk of SARS-CoV-2 infection. Discussion: Anti-S antibody titre showed a dose-dependent protective effect but did not fully account for the protection provided by vaccination or past infection, indicating that other mechanisms of protection are also involved.

The real-world impact of the COVID-19 pandemic on patients with cancer: a multidisciplinary cross-sectional survey.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented disruptions to cancer care worldwide. We conducted a multidisciplinary survey of the real-world impact of the pandemic, as perceived by patients with cancer. METHODS: A total of 424 patients with cancer were surveyed using a 64-item questionnaire constructed by a multidisciplinary panel. The questionnaire examined patient perspectives regarding COVID-19-related effects (eg, social distancing measures) on cancer care delivery, resources, and healthcare-seeking behaviour, along with the physical and psychosocial aspects of patient well-being and pandemic-related psychological repercussions. RESULTS: Overall, 82.8% of respondents believed that patients with cancer are more susceptible to COVID-19; 65.6% expected that COVID-19 would delay anti-cancer drug development. Although only 30.9% of respondents felt that hospital attendance was safe, 73.1% expressed unaltered willingness to attend scheduled appointments; 70.3% of respondents preferred to receive chemotherapy as planned, and 46.5% were willing to accept changes in efficacy or side-effect profile to allow an outpatient regimen. A survey of oncologists revealed significant underestimation of patient motivation to avoid treatment interruptions. Most surveyed patients felt that there was an insufficient amount of information available concerning the impact of COVID-19 on cancer care, and most patients reported social distancing-related declines in physical, psychological, and dietary wellness. Sex, age, education level, socio-economic status, and psychological risk were significantly associated with patient perceptions and preferences. CONCLUSION: This multidisciplinary survey concerning the effects of the COVID-19 pandemic revealed key patient care priorities and unmet needs. These findings should be considered when delivering cancer care during and after the pandemic.

Spatiotemporal characteristics of ozone and the formation sensitivity over the Fenwei Plain.

High surface ozone (O3) levels affect human and environmental health. The Fenwei Plain (FWP), one of the critical regions for China's "Blue Sky Protection Campaign", has reported severe O3 pollution. This study investigates the spatiotemporal properties and the causes of O3 pollution over the FWP using high-resolution data from the TROPOspheric Monitoring Instrument (TROPOMI) from 2019 to 2021. This study characterizes spatial and temporal variations in O3 concentration by linking O3 columns and surface monitoring using a trained deep forest machine learning model. O3 concentrations in summer were 2-3 times higher than those found in winter due to higher temperatures and greater solar irradiation. The spatial distributions of O3 correlate with the solar radiation showing decreased trends from the northeastern to the southwestern FWP, with the highest O3 values in Shanxi Province and the lowest in Shaanxi Province. For urban areas, croplands and grasslands, the O3 photochemistry in summer is NOx-limited or in the transitional regime, while it is VOC-limited in winter and other seasons. Reducing NOx emissions would be effective for decreasing O3 levels in summer, while VOC reductions are necessary for winter. The annual cycle in vegetated areas included both NOx-limited and transitional regimes, indicating the importance of NOx controls to protect ecosystems. The O3 response to limiting precursors shown here is of importance for optimizing control strategies and is illustrated by emission changes during the 2020 COVID-19 outbreak.

A non-invasive method for the assessment of gingival thickness in the aesthetic zone and the concept of the gingival geometric ratio in an Asian population.

The aim of this study was to investigate the gingival thickness and biologic width in the aesthetic zone (maxillary central and lateral incisors) in an Asian population using cone beam computed tomography (CBCT) as a non-invasive measurement method, prior to immediate implant placement. The gingival geometric ratio is introduced as a new parameter for assessing soft tissue stability and hence predicting the aesthetic outcome. The gingival thickness, biologic width category (normal, high, and low crest), and gingival geometric ratio (shape and configuration of the gingival tissues) were assessed for 171 central and 175 lateral incisors on high-resolution CBCT images. Thick gingivae were found in 93.6% of the central incisors and 64% of the lateral incisors (P < 0.001). The difference in thickness between the central and lateral incisors was statistically significant (P < 0.001). Regarding the biologic width of the facial gingival tissue, the majority of central (64.8%) and lateral (64.3%) incisors were categorized as low crest (>3 mm). The study found that most of the gingivae of the maxillary central incisors were thick, while thin gingivae were more prevalent in the lateral incisors. Therefore, an individual patient may have different gingival thickness types, and 'one individual, one gingival biotype' may not be true. Furthermore, the majority of the facial gingival tissues of the maxillary incisors were found to be low crest.

Very low risk of monkeypox among staff and students after exposure to a confirmed case in educational settings, England, May to July 2022.

We investigated a secondary school (11-16 year-olds), a primary school (5-11 year-olds), reception year (4-5 year-olds) and a nursery (2-5 year-olds) following confirmed monkeypox in an adult in each educational setting during June and July 2022. MVA-BN vaccine was offered up to 14 days post exposure to 186 children < 12 years and 21 were vaccinated. No secondary cases occurred among at least 340 exposed students and more than 100 exposed staff during the 28-day follow-up period.

The role of adjuvant radiation therapy in older patients with node-positive vulvar cancer: A national cancer database analysis.

OBJECTIVE: We sought to evaluate whether the survival benefit of adjuvant radiotherapy in patients with node-positive vulvar cancer is maintained in older patients, who comprise a large subgroup of patients with vulvar cancer. METHODS: The National Cancer Database (NCDB) was queried for patients aged 65 years or older, who were diagnosed with vulvar squamous cell carcinoma from 2004 to 2017 and underwent surgery with confirmed node-positive disease. Statistical analysis was performed with propensity-score matching, chi-square test, log-rank test, Kaplan-Meier, and multivariable Cox proportional regression. RESULTS: A total of 2396 patients were analyzed, and 1517 (63.3%) received adjuvant radiotherapy. Median follow-up was 73 months. Median age at diagnosis was 77 years (range 65-90). In the propensity score-matched cohort, five-year overall survival (OS) was 29%. Five-year OS was 33% in patients who received surgery followed by adjuvant radiotherapy and 26% in patients who received surgery alone (p < 0.0001). Multivariable analysis continued to demonstrate a survival benefit associated with the addition of adjuvant radiotherapy (OR 0.77 [95% CI 0.69-00.87], p < 0.001). Adjuvant radiotherapy was associated with improved OS among patients aged 65-84 (5-year OS 35% vs 29%, p = 0.0004), but not in patients aged 85 years and older (5-year OS 20% vs 19%, p = 0.32). CONCLUSION: This NCDB study suggests that in older patients with node-positive vulvar cancer, radiotherapy continues to be a vital component of multimodality therapy. However, a comprehensive and geriatrics-specific approach is crucial for treating older adults with node-positive vulvar cancer, as the benefit of adjuvant radiotherapy may be compromised by treatment-related morbidity/toxicity.

SARS-CoV-2-specific memory B cells can persist in the elderly who have lost detectable neutralizing antibodies.

Memory B cells (MBCs) can provide a recall response able to supplement waning antibodies (Abs) with an affinity-matured response better able to neutralize variant viruses. We studied a cohort of elderly care home residents and younger staff (median age of 87 years and 56 years, respectively), who had survived COVID-19 outbreaks with only mild or asymptomatic infection. The cohort was selected because of its high proportion of individuals who had lost neutralizing antibodies (nAbs), thus allowing us to specifically investigate the reserve immunity from SARS-CoV-2-specific MBCs in this setting. Class-switched spike and receptor-binding domain (RBD) tetramer-binding MBCs persisted 5 months after mild or asymptomatic SARS-CoV-2 infection, irrespective of age. The majority of spike- and RBD-specific MBCs had a classical phenotype, but we found that activated MBCs, indicating possible ongoing antigenic stimulation or inflammation, were expanded in the elderly group. Spike- and RBD-specific MBCs remained detectable in the majority of individuals who had lost nAbs, although at lower frequencies and with a reduced IgG/IgA isotype ratio. Functional spike-, S1 subunit of the spike protein- (S1-), and RBD-specific recall was also detectable by enzyme-linked immune absorbent spot (ELISPOT) assay in some individuals who had lost nAbs, but was significantly impaired in the elderly. Our findings demonstrate that a reserve of SARS-CoV-2-specific MBCs persists beyond the loss of nAbs but highlight the need for careful monitoring of functional defects in spike- and RBD-specific B cell immunity in the elderly.

Reinfection with new variants of SARS-CoV-2 after natural infection: a prospective observational cohort in 13 care homes in England.

BACKGROUND: Understanding the duration of protection and risk of reinfection after natural infection is crucial to planning COVID-19 vaccination for at-risk groups, including care home residents, particularly with the emergence of more transmissible variants. We report on the duration, neutralising activity, and protection against the alpha variant of previous SARS-CoV-2 infection in care home residents and staff infected more than 6 months previously. METHODS: We did this prospective observational cohort surveillance in 13 care homes in Greater London, England. All staff and residents were included. Staff and residents had regular nose and throat screening for SARS-CoV-2 by RT-PCR according to national guidelines, with ad hoc testing of symptomatic individuals. From January, 2021, antigen lateral flow devices were also used, but positive tests still required RT-PCR confirmation. Staff members took the swab samples for themselves and the residents. The primary outcome was SARS-CoV-2 RT-PCR positive primary infection or reinfection in previously infected individuals, as determined by previous serological testing and screening or diagnostic RT-PCR results. Poisson regression and Cox proportional hazards models were used to estimate protective effectiveness of previous exposure. SARS-CoV-2 spike, nucleoprotein, and neutralising antibodies were assessed at multiple timepoints as part of the longitudinal follow-up. FINDINGS: Between April 10 and Aug 3, 2020, we recruited and tested 1625 individuals (933 staff and 692 residents). 248 participants were lost to follow-up (123 staff and 125 residents) and 1377 participants were included in the follow-up period to Jan 31, 2021 (810 staff and 567 residents). There were 23 reinfections (ten confirmed, eight probable, five possible) in 656 previously infected individuals (366 staff and 290 residents), compared with 165 primary infections in 721 susceptible individuals (444 staff and 277 residents). Those with confirmed reinfections had no or low neutralising antibody concentration before reinfection, with boosting of titres after reinfection. Kinetics of binding and neutralising antibodies were similar in older residents and younger staff. INTERPRETATION: SARS-CoV-2 reinfections were rare in older residents and younger staff. Protection from SARS-CoV-2 was sustained for longer than 9 months, including against the alpha variant. Reinfection was associated with no or low neutralising antibody before reinfection, but significant boosting occurred on reinfection. FUNDING: Public Health England.

Bilateral idiopathic corneal opacity: A report of Ascher ring and a review of the literature.

PURPOSE: To present a case of a rare entity of Ascher ring, a bilateral corneal stromal opacification. OBSERVATION: A 70-year-old male with no ocular history who presented for cataract evaluation was found to have idiopathic bilateral circular stromal corneal rings. CONCLUSIONS: After completion of extensive history, examination, imaging analyses, and laboratory studies for workup of corneal opacities, we arrived at a diagnosis of Ascher corneal ring, an extremely rare entity. IMPORTANCE: A rare entity should be considered after excluding other etiologies.

Cross sectional investigation of a COVID-19 outbreak at a London Army barracks: Neutralising antibodies and virus isolation.

BACKGROUND: Military personnel in enclosed societies are at increased risk of respiratory infections. We investigated an outbreak of Coronavirus Disease 2019 in a London Army barracks early in the pandemic. METHODS: Army personnel, their families and civilians had nasal and throat swabs for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by reverse transcriptase -polymerase chain reaction (RT-PCR), virus isolation and whole genome sequencing, along with blood samples for SARS-CoV-2 antibodies. All tests were repeated 36 days later. FINDINGS: During the first visit, 304 (254 Army personnel, 10 family members, 36 civilians, 4 not stated) participated and 24/304 (8%) were SARS-CoV-2 RT-PCR positive. Infectious virus was isolated from 7/24 (29%). Of the 285 who provided a blood sample, 7% (19/285) were antibody positive and 63% (12/19) had neutralising antibodies. Twenty-two (22/34, 64%) individuals with laboratory-confirmed infection were asymptomatic. Nine SARS-CoV-2 RT-PCR positive participants were also antibody positive but those who had neutralising antibodies did not have infectious virus. At the second visit, no new infections were detected, and 13% (25/193) were seropositive, including 52% (13/25) with neutralising antibodies. Risk factors for SARS-CoV-2 antibody positivity included contact with a confirmed case (RR 25.2; 95% CI 14-45), being female (RR 2.5; 95% CI 1.0-6.0) and two-person shared bathroom (RR 2.6; 95% CI 1.1-6.4). INTERPRETATION: We identified high rates of asymptomatic SARS-CoV-2 infection. Public Health control measures can mitigate spread but virus re-introduction from asymptomatic individuals remains a risk. Most seropositive individuals had neutralising antibodies and infectious virus was not recovered from anyone with neutralising antibodies. FUNDING: PHE.

Infection and transmission of SARS-CoV-2 in London care homes reporting no cases or outbreaks of COVID-19: Prospective observational cohort study, England 2020.

BACKGROUND: Care homes have been disproportionately affected by the COVID-19 pandemic. We investigated the potential role of asymptomatic infection and silent transmission in London care homes that reported no cases of COVID-19 during the first wave of the pandemic. METHODS: Five care homes with no cases and two care homes reporting a single case of COVID-19 (non-outbreak homes) were investigated with nasal swabbing for SARS-CoV-2 RT-PCR and serology for SARS-CoV-2 antibodies five weeks later. Whole genome sequencing (WGS) was performed on RT-PCR positive samples. Serology results were compared with those of six care homes with recognised outbreaks. FINDINGS: Across seven non-outbreak homes, 718 (387 staff, 331 residents) individuals had a nasal swab and 651 (386 staff, 265 residents) had follow-up serology. Sixteen individuals (13 residents, 3 staff) in five care homes with no reported cases were RT-PCR positive (care home positivity rates, 0 to 7.6%) compared to 13 individuals (3.0 and 10.8% positivity) in two homes reporting a single case.Seropositivity across these seven homes varied between 10.7-56.5%, with four exceeding community seroprevalence in London (14.8%). Seropositivity rates for staff and residents correlated significantly (rs 0.84, [95% CI 0.51-0.95] p <0.001) across the 13 homes. WGS identified multiple introductions into some homes and silent transmission of a single lineage between staff and residents in one home. INTERPRETATION: We found high rates of asymptomatic infection and transmission even in care homes with no COVID-19 cases. The higher seropositivity rates compared to RT-PCR positivity highlights the true extent of the silent outbreak. FUNDING: PHE.

Outcomes of Subliminal Transscleral Cyclophotocoagulation treatment in glaucoma.

BACKGROUND: Subliminal transscleral cyclophotocoagulation (SL-TSCPC) is a new alternative therapy to reduce intraocular pressure (IOP) safely and effectively. However, there are few studies regarding SL-TSCPC by Supra 810 laser machine and limited data regarding its effectiveness in moderate severity glaucoma that still has good preservation of vision. This study was conducted to evaluate the outcome of SL-TSPCPC in various types of glaucoma including patients with good vision. METHODS: A retrospective, non-comparative, analytical case series of all patients who received SL-TSCPC treatment from October 2018 to April 2019 at Hospital Tengku Ampuan Afzan, Pahang, Malaysia. Data was collected during the second week, sixth week, third month and sixth month follow-up. The primary outcome measure gave success rate at six months post-treatment. Secondary measures were changes in visual acuity, mean IOP reduction, mean number of IOP lowering medications reduced and ocular side effects noted during follow-up. RESULTS: The success rate was 43.8% (seven eyes out of sixteen eyes) at six months post-treatment. The mean IOP reduced from 43.0mmHg±14.8mmHg pre-treatment to 24.7mmHg±12.0mmHg at two weeks post treatment with 42.6% reduction. Subsequently, mean IOP at sixth week, third month and sixth month were 33.8mmHg±16.9mmHg, 35.2mmHg±14.9mmHg, and 29.0mmHg±16.2mmHg respectively. Vision maintained in 13 patients, two patients had improvement in vision however, five patients had deterioration in vision. No serious ocular side effects were noted. CONCLUSION: Subliminal TSCPC is a safe and alternative method of lowering IOP in moderate to advanced glaucoma over 6 months duration of follow-up. As it has good safety profile and repeatability, it is a good treatment option for patients with uncontrolled glaucoma.

Antibodies to SARS-CoV-2 protect against re-infection during outbreaks in care homes, September and October 2020.

Two London care homes experienced a second COVID-19 outbreak, with 29/209 (13.9%) SARS-CoV-2 RT-PCR-positive cases (16/103 residents, 13/106 staff). In those with prior SARS-CoV-2 exposure, 1/88 (1.1%) individuals (antibody positive: 87; RT-PCR-positive: 1) became PCR-positive compared with 22/73 (30.1%) with confirmed seronegative status. After four months protection offered by prior infection against re-infection was 96.2% (95% confidence interval (CI): 72.7-99.5%) using risk ratios from comparison of proportions and 96.1% (95% CI: 78.8-99.3%) using a penalised logistic regression model.

High prevalence of SARS-CoV-2 antibodies in care homes affected by COVID-19: Prospective cohort study, England.

BACKGROUND: We investigated six London care homes experiencing a COVID-19 outbreak and found high rates of SARS-CoV-2 infection among residents and staff. Here we report follow-up investigations including antibody testing in the same care homes five weeks later. METHODS: Residents and staff in the initial investigation had a repeat nasal swab for SARS-CoV-2 RT-PCR and a blood test for SARS CoV-2 antibodies using ELISA based on SARS-CoV-2 native viral antigens derived from infected cells and virus neutralisation. FINDINGS: Of the 518 residents and staff in the initial investigation, 186/241 (77.2%) surviving residents and 208/254 (81.9%) staff underwent serological testing. Almost all SARS-CoV-2 RT-PCR positive residents and staff were seropositive five weeks later, whether symptomatic (residents 35/35, 100%; staff, 22/22, 100%) or asymptomatic (residents 32/33, 97.0%; staff 21/22, 95.5%). Symptomatic but SARS-CoV-2 RT-PCR negative residents and staff also had high seropositivity rates (residents 23/27, 85.2%; staff 18/21, 85.7%), as did asymptomatic RT-PCR negative individuals (residents 61/91, 67.0%; staff 95/143, 66.4%). Neutralising antibody was detected in 118/132 (89.4%) seropositive individuals and was not associated with age or symptoms. Ten residents (10/79 re-tested, 12.7%) remained RT-PCR positive but with higher RT-PCR cycle threshold values; 7/10 had serological testing and all were seropositive. New infections were detected in three residents and one staff. INTERPRETATION: RT-PCR provides a point prevalence of SARS-CoV-2 infection but significantly underestimates total exposure in outbreak settings. In care homes experiencing large COVID-19 outbreaks, most residents and staff had neutralising SARS-CoV-2 antibodies, which was not associated with age or symptoms. FUNDING: PHE.

Investigation of SARS-CoV-2 outbreaks in six care homes in London, April 2020.

BACKGROUND: Care homes are experiencing large outbreaks of COVID-19 associated with high case-fatality rates. We conducted detailed investigations in six London care homes reporting suspected COVID-19 outbreaks during April 2020. METHODS: Residents and staff had nasal swabs for SARS CoV-2 testing using RT-PCR and were followed-up for 14 days. They were categorized as symptomatic, post-symptomatic or pre-symptomatic if they had symptoms at the time of testing, in the two weeks before or two weeks after testing, respectively, or asymptomatic throughout. Virus isolation and whole genome sequencing (WGS) was also performed. FINDINGS: Across the six care homes, 105/264 (39.8%) residents were SARS CoV-2 positive, including 28 (26.7%) symptomatic, 10 (9.5%) post-symptomatic, 21 (20.0%) pre-symptomatic and 46 (43.8%) who remained asymptomatic. Case-fatality at 14-day follow-up was highest among symptomatic SARS-CoV-2 positive residents (10/28, 35.7%) compared to asymptomatic (2/46, 4.3%), post-symptomatic (2/10, 20.0%) or pre-symptomatic (3/21,14.3%) residents. Among staff, 53/254 (20.9%) were SARS-CoV-2 positive and 26/53 (49.1%) remained asymptomatic. RT-PCR cycle-thresholds and live-virus recovery were similar between symptomatic/asymptomatic residents/staff. Higher RT-PCR cycle threshold values (lower virus load) samples were associated with exponentially decreasing ability to recover infectious virus (P<0.001). WGS identified multiple (up to 9) separate introductions of different SARS-CoV-2 strains into individual care homes. INTERPRETATION: A high prevalence of SARS-CoV-2 positivity was found in care homes residents and staff, half of whom were asymptomatic and potential reservoirs for on-going transmission. A third of symptomatic SARS-CoV-2 residents died within 14 days. Symptom-based screening alone is not sufficient for outbreak control. FUNDING: None.

Increased risk of SARS-CoV-2 infection in staff working across different care homes: enhanced CoVID-19 outbreak investigations in London care Homes.

BACKGROUND: Care homes have been disproportionately affected by the COVID-19 pandemic and continue to suffer large outbreaks even when community infection rates are declining, thus representing important pockets of transmission. We assessed occupational risk factors for SARS-CoV-2 infection among staff in six care homes experiencing a COVID-19 outbreak during the peak of the pandemic in London, England. METHODS: Care home staff were tested for SARS-COV-2 infection by RT-PCR and asked to report any symptoms, their contact with residents and if they worked in different care homes. Whole genome sequencing (WGS) was performed on RT-PCR positive samples. RESULTS: In total, 53 (21%) of 254 staff were SARS-CoV-2 positive but only 12/53 (23%) were symptomatic. Among staff working in a single care home, SARS-CoV-2 positivity was 15% (2/13), 16% (7/45) and 18% (30/169) in those reporting no, occasional and regular contact with residents. In contrast, staff working across different care homes (14/27, 52%) had a 3.0-fold (95% CI, 1.9-4.8; P<0.001) higher risk of SARS-CoV-2 positivity than staff working in single care homes (39/227, 17%). WGS identified SARS-CoV-2 clusters involving staff only, including some that included staff working across different care homes. CONCLUSIONS: SARS-CoV-2 positivity was significantly higher among staff working across different care homes than those who were working in the same care home. We found local clusters of SARS-CoV-2 infection between staff only, including those with minimal resident contact. Infection control should be extended for all contact, including those between staff, whilst on care home premises.

Adjuvant radiation followed by chemotherapy is associated with improved overall survival in endometrial cancer.

OBJECTIVE: Although multimodality therapy has been shown to improve outcomes for patients with high-risk endometrial carcinoma, optimal type and timing of adjuvant therapies is unknown. METHODS: Patients with stage I-IVA endometrial carcinoma diagnosed from 2004 to 2015, and treated with surgery, chemotherapy, and radiation were identified in the National Cancer Database. Adjuvant treatment was categorized as sequential radiation followed by chemotherapy (RT-CT), concurrent chemoradiation (CCRT, RT and CT started within 7 days), or sequential chemotherapy followed by radiation (CT-RT). Analysis for propensity score matched (PSM) cohorts comparing RT-CT to CCRT and CT-RT groups was additionally performed. RESULTS: A total of 17,070 patients were identified, including 12,402 (72.7%) treated with RT-CT, 2,153 (12.6%) with CCRT, and 2,515 (14.7%) with CT-RT. Median follow-up was 44.3 months. Five-year overall-survival (OS) by adjuvant treatment regimen was 77.3% (95% CI 76.4%-78.2%), 74.3% (95% CI 72.0%-76.3%), and 74.4% (95% CI 72.5%-76.3%), respectively (p < .001). When unmatched cohorts were stratified by stage, adjuvant RT-CT was associated with improved OS in stage I and III patients. A similar survival advantage associated with RT-CT was observed in PSM cohorts comparing RT-CT group to CCRT/CT-RT group (5-year OS 77.4% vs 74.2%, p = .001). However, the difference in OS was significant only among stage III patients (RT-CT 73.9% compared to CCRT/CT-RT 69.7%, p =.002). CONCLUSION: Our findings suggest survival benefit with adjuvant RT-CT compared to CT-RT or CCRT in patients undergoing trimodality therapy for endometrial cancer. This survival benefit may be limited to stage III patients.

Emergence of dominant toxigenic M1T1 Streptococcus pyogenes clone during increased scarlet fever activity in England: a population-based molecular epidemiological study.

BACKGROUND: Since 2014, England has seen increased scarlet fever activity unprecedented in modern times. In 2016, England's scarlet fever seasonal rise coincided with an unexpected elevation in invasive Streptococcus pyogenes infections. We describe the molecular epidemiological investigation of these events. METHODS: We analysed changes in S pyogenes emm genotypes, and notifications of scarlet fever and invasive disease in 2014-16 using regional (northwest London) and national (England and Wales) data. Genomes of 135 non-invasive and 552 invasive emm1 isolates from 2009-16 were analysed and compared with 2800 global emm1 sequences. Transcript and protein expression of streptococcal pyrogenic exotoxin A (SpeA; also known as scarlet fever or erythrogenic toxin A) in sequenced, non-invasive emm1 isolates was quantified by real-time PCR and western blot analyses. FINDINGS: Coincident with national increases in scarlet fever and invasive disease notifications, emm1 S pyogenes upper respiratory tract isolates increased significantly in northwest London in the March to May period, from five (5%) of 96 isolates in 2014, to 28 (19%) of 147 isolates in 2015 (p=0·0021 vs 2014 values), to 47 (33%) of 144 in 2016 (p=0·0080 vs 2015 values). Similarly, invasive emm1 isolates collected nationally in the same period increased from 183 (31%) of 587 in 2015 to 267 (42%) of 637 in 2016 (p<0·0001). Sequences of emm1 isolates from 2009-16 showed emergence of a new emm1 lineage (designated M1UK)-with overlap of pharyngitis, scarlet fever, and invasive M1UK strains-which could be genotypically distinguished from pandemic emm1 isolates (M1global) by 27 single-nucleotide polymorphisms. Median SpeA protein concentration in supernatant was nine-times higher among M1UK isolates (190·2 ng/mL [IQR 168·9-200·4]; n=10) than M1global isolates (20·9 ng/mL [0·0-27·3]; n=10; p<0·0001). M1UK expanded nationally to represent 252 (84%) of all 299 emm1 genomes in 2016. Phylogenetic analysis of published datasets identified single M1UK isolates in Denmark and the USA. INTERPRETATION: A dominant new emm1 S pyogenes lineage characterised by increased SpeA production has emerged during increased S pyogenes activity in England. The expanded reservoir of M1UK and recognised invasive potential of emm1 S pyogenes provide plausible explanation for the increased incidence of invasive disease, and rationale for global surveillance. FUNDING: UK Medical Research Council, UK National Institute for Health Research, Wellcome Trust, Rosetrees Trust, Stoneygate Trust.

The association of postnatal urinary tract dilation risk score with clinical outcomes.

BACKGROUND: There are limited data on the predictive value of the consensus urinary tract dilation (UTD) score with respect to subsequent clinical diagnoses. We sought to define the relationship between postnatal UTD risk score and clinical outcomes during childhood. METHODS: Complete ultrasound image sets from a random selection of infants aged 0-90 days undergoing initial ultrasound at a single institution for prenatal hydronephrosis between 2012 and 2014 were assigned a UTD score by 1 pediatric urologist and 1 pediatric radiologist. Urinary tract dilation risk score was analyzed for association with a composite outcome comprising urinary tract infection, vesicoureteral reflux (VUR), ureteropelvic junction obstruction, non-refluxing megaureter (NRM), ureterocele, bladder outlet obstruction (BOO), and chronic kidney disease. Surgical intervention and resolution of UTD were evaluated separately. Descriptive and survival analyses were performed. RESULTS: Urinary tract dilation scores for 494 subjects were P0 in 23.5%, P1 in 26.5%, P2 in 23.5%, and P3 in 26.5%. Seventy-four percent were male. Median age at initial imaging was 28 days; median follow-up was 19.8 months. The composite outcome occurred in 138 of 494 patients (27.9%) and varied significantly (p < 0.001) by UTD score: 11.2% for P0, 10.7% for P1, 29.3% for P2, and 58.8% for P3. On survival analysis (Summary Figure), higher UTD grade was significantly associated with the composite outcome (hazard ratio for P3 vs. P0 was 7.4 [95% CI: 3.44-15.92, p < 0.001]). Urinary tract infection and VUR diagnosis varied by UTD score (p = 0.03 and p < 0.001, respectively). Ureteropelvic junction obstruction was diagnosed (based on MAG3 results) in 6.3% of patients, 84% of whom were P3. Non-refluxing megaureter was diagnosed in 7.7%. Ureterocele and BOO were uncommon (1.4%, and 0.6%, respectively). Surgical intervention was also associated with UTD risk, with 46% of P3 undergoing surgery vs. 1% of P0, 1% of P1, and 6% of P2 (p < 0.001). Resolution of UTD occurred in 41% (median 10.1 months) and varied significantly by UTD risk (p < 0.001). DISCUSSION: Urinary tract dilation risk score is associated with clinical events, although ascertainment bias may influence some of the differences in outcomes, particularly for VUR, because VCUG utilization varied by the UTD group. The lack of any significant difference in outcomes between patients with UTD P0 versus P1 suggests that the P1 category could be eliminated as it does not meaningfully distinguish between outcome risk. CONCLUSIONS: Higher UTD risk scores are strongly associated with genitourinary diagnoses during the first two years of life.