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BackgroundThe majority of combat deaths occur in the prehospital setting. Efforts to increase survival including blood transfusions are made in the prehospital setting. The blood products available in the Role 1 setting include whole blood (WB), red blood cells (RBCs), fresh frozen plasma (FFP), and lyophilized (freeze-dried) plasma (FDP).MethodsThis is a secondary analysis of a previously published dataset within the Prehospital Trauma Registry (PHTR) from 2003 through May 2019. Deterministic linking was used when possible with the DoD Trauma Registry for outcome data. Descriptive statistics were used to analyze the data.ResultsWe identified 1,357 patient encounters in the PHTR. Within that group, 28 patients received a prehospital blood product, with 41 total administrations: WB (18), RBCs (12), FFP (6), FDP (3), and blood not otherwise specified (2). Outcome data were available for 17 of the 28 patients. The median injury severity score was 20, with the thorax being the most frequent seriously injured body region. Most (94%) patients survived to discharge. The median ICU days was 11 (Interquartile Range [IQR] 3-19), and the median hospital days was 19 (IQR 8-29). The average volume (units) of RBCs was 6.0 (95% CI 1.9-10.1), WB 2.8 (95% CI 0.0-5.6), platelets 0.7 (95% CI 0.0-1.4), and FFP 5.0 (95% CI 1.2-8.8).ConclusionsThe use of prehospital blood products is uncommon in U.S. combat settings. Patients who received blood products sustained severe injuries but had a high survival rate. Given the infrequent but critical use and potentially increased need for adequate prolonged casualty care in future near-peer conflicts, optimizing logistical chain circulation is required.

Aims Prediction of mitral (MR) and tricuspid (TR) regurgitation progression on transthoracic echocardiography (TTE) is needed to personalize valvular surveillance intervals and prognostication. Methods and results Structured TTE report data at Beth Israel Deaconess Medical Center, 26 January 2000–31 December 2017, were used to determine time to progression (≥1+ increase in severity). TTE predictors of progression were used to create a progression score, externally validated at Massachusetts General Hospital, 1 January 2002–31 December 2019. In the derivation sample (MR, N = 34 933; TR, N = 27 526), only 5379 (15.4%) individuals with MR and 3630 (13.2%) with TR had progression during a median interquartile range) 9.0 (4.1–13.4) years of follow-up. Despite wide inter-individual variability in progression rates, a score based solely on demographics and TTE variables identified individuals with a five- to six-fold higher rate of MR/TR progression over 10 years (high- vs. low-score tertile, rate of progression; MR 20.1% vs. 3.3%; TR 21.2% vs. 4.4%). Compared to those in the lowest score tertile, those in the highest tertile of progression had a four-fold increased risk of mortality. On external validation, the score demonstrated similar performance to other algorithms commonly in use. Conclusion Four-fifths of individuals had no progression of MR or TR over two decades. Despite wide interindividual variability in progression rates, a score, based solely on TTE parameters, identified individuals with a five- to six-fold higher rate of MR/TR progression. Compared to the lowest tertile, individuals in the highest score tertile had a four-fold increased risk of mortality. Prediction of long-term MR/TR progression is not only feasible but prognostically important.

The purpose of this study was to determine the patient radiation dose in combined whole-body positron emission tomography/computed tomography (PET/CT) examinations performed in the largest tertiary hospital in Greece. Computed tomography dose index (CTDIvol), dose length product (DLP), weight, height and administered activity of 2-[18F] fluoro-2-deoxy-D-glucose values for PET/CT examinations were recorded in a sample of 1014 randomly selected patients. The mean (±standard deviation) and median (interquartile) CTDIvol values were equal to 5.5 ± 2.4 and 4.8 (2.5) mGy, respectively. The respective DLP values were 483.3 ± 212.4 and 426 (234.6) mGy·cm. For the administered activity, mean and median were equal to 363.9 ± 68.3 and 361.6 (85.6) MBq. The mean administered activity per body weight was 4.8 ± 0.6 and the median 4.8 (0.6) MBq/kg. The results of this survey are within the range of values reported in the literature and can be used as a standard of reference until national diagnostic reference levels are established for whole-body PET/CT procedures.

Objectives RA patients who fail to respond to MTX can receive biologic dMARDs (bDMARDs). The Torque Teno Virus (TTV) is a potential novel candidate for monitoring of immunosuppression. We explore TTV in these patients and its association with clinical response to bDMARDs. Methods The BioBio Study is a multicentre randomized open-label trial, including RA patients with insufficient response to MTX. Patients were randomized to either TNFi (infliximab, INF), anti-IL-6 (tocilizumab, TCZ), CTLA4-Ig (abatacept, ABA) or anti-CD20 (rituximab, RTX) in addition to MTX. PCR was used to quantify TTV in the peripheral blood. Results TTV was measured in 95 patients (INF, n = 23; TCZ, n = 22; ABA, n = 27; RTX; n = 23). TTV increased by a median of 4.5 × 104 copies/ml [c/ml; interquartile range (IQR) 0–7.5 × 105] after 3 months. TTV levels at month 3 were associated with the Simplified Disease Activity Index (SDAI) (P = 0.03) and the Clinical Disease Activity Index (CDAI) response (P = 0.026) at month 6. A TTV cut-off level of 1.2 × 106 c/ml at month 3 had a positive likelihood ratio of 2.7 for prediction of an 85% reduction in SDAI at month 6. Conclusion Our data suggest that TTV levels increase upon TNF, CD20 and costimulation blockade and are associated with the clinical response to bDMARDs in RA patients. Trial registration ClinicalTrials.gov; https://clinicaltrials.gov; NCT01638715

Aim To describe clinical characteristics, procedural details, specific challenges, and outcomes in patients with HeartMate3™ (HM3), a left ventricular assist device system with a magnetically levitated pump, undergoing ventricular tachycardia ablation (VTA). Methods and results Data were collected from patients with an HM3 system who underwent VTA in seven tertiary centres. Data included baseline patient characteristics, procedural data, mortality, and arrhythmia-free survival. The study cohort included 19 patients with cardiomyopathy presenting with ventricular tachycardia (VT) (53% with VT storm). Ventricular tachycardias were induced in 89% of patients and a total of 41 VTs were observed. Severe electromagnetic interference was present on the surface electrocardiogram. Hence, VT localization required analysis of intra-cardiac signals or the use of filter in the 40–20 Hz range. The large house pump HM3 design obscured the cannula inflow and therefore multi imaging modalities were necessary to avoid catheter entrapment in the cannula. A total of 32 VTs were mapped and were successfully ablated (31% to the anterior wall, 38% to the septum and only 9% to the inflow cannula region). Non-inducibility of any VT was reached in 11 patients (58%). Over a follow-up of 429 (interquartile range 101–692) days, 5 (26%) patients underwent a redo VT ablation due to recurrent VTA and 2 (11%) patients died. Conclusions Ventricular tachycardia ablation in patients with HM3 is feasible and safe when done in the appropriate setup. Long-term arrhythmia-free survival is acceptable but not well predicted by non-inducibility at the end of the procedure.

Aims Cardiac arrhythmias have been associated with intense solar and geomagnetic activity (SGA) and exposures to air pollution. Methods and results We examined whether oscillations of SGA can modify the effect of hourly exposures to air pollutants on atrial fibrillation ≥30 s (AF) risk in patients with dual-chamber implantable cardioverter-defibrillators. The effects of SGA on ambient particulate matter 50th percentile in IMF, SW, and Kp index) enhanced the effects of all three air pollutants on AF, while during periods of reduced SGA the associations were considerably weaker or absent. During periods of intense SW 6 h prior to an AF event, the odds ratio (OR) for PM2.5 exposure per interquartile range (IQR) of 5.6 µg/m3 was 1.7 [95% confident interval (CI) 1.3–2.3, P = 0.0001]. For periods of reduced SW, the OR for PM2.5 exposure per IQR was 1.2 (95% CI 0.9–1.5; P = 0.27). There were similar effects for PN and BC exposures. In patients with multiple AF events per hour, the associations with air pollutants during intense SGA were even greater. Conclusion The effects of air pollutants up to 24 h before AF events were enhanced during periods of increased SGA. Our results suggest that these effects may account for variation in AF risk.

OBJECTIVES Thoracic endovascular aortic repair (TEVAR) is the first-line therapy in acute complicated type B aortic dissections (cTBAD). Nevertheless, no evidence-based consensus on the optimal measurement technique and sizing for TEVAR in cTBAD exists. The aim was to evaluate how different measurement and sizing techniques for TEVAR affect long-term outcomes. METHODS Retrospective analysis investigating the association between sizing and postoperative results after TEVAR in patients with cTBAD, treated between January 2003 and December 2020. Diameter measurements were performed perpendicular to a centreline in pre-interventional Computed tomography angiographies. Oversizing was determined by measuring aortic diameter in zone 2 of the aortic arch in relation to the implanted stent graft, and categorized into 2 sizing groups (≤10% and >10%). The primary outcome was freedom from aortic-related events. Secondary outcomes included mortality and a comparison of 3 alternative measurement techniques considering the estimated pre-dissection diameter. RESULTS Fifty-seven patients (median age 69, interquartile range 59.6–78.2 years) were included. Stent graft oversizing by ≤10% showed a trend towards fewer aortic-related events hazard ratio 0.455 (95% confidence interval 0.128–1.624, P = 0.225). The 3 measurement techniques using the pre-dissection aortic diameter differed by a mean of 1.7–4.0 mm with a variability of up to 8.4 mm. In none of the 57 patients, the same stent graft would have been chosen based on the different measurement techniques using an oversizing ≤10%. CONCLUSIONS TEVAR oversizing of ≤10% in patients with cTBAD might reduce aortic-related events up to 50%. Consensus on measurement techniques of the pre-dissection aortic diameter and stent graft sizing is of paramount importance.

OBJECTIVES Few data exist on the use of del Nido cardioplegia in adults, specifically during operations requiring prolonged aortic cross-clamp. In this pilot study, we evaluate outcomes of patients undergoing surgery with cross-clamp time >3 h based on re-dosing strategy, using either full dose (FD; 1:4 blood to crystalloid ratio) or dilute (4:1 blood to crystalloid ratio) solution. METHODS Consecutive adult patients (>18 years) undergoing cardiac surgery from 2012 to 2018 with cross-clamp time >3 h were reviewed. Patients were excluded if del Nido cardioplegia was not used. Patients were categorized into FD or dilute groups based on re-dosing solution. Propensity score matching was used to control for baseline differences between groups. The primary endpoint was in-hospital mortality. Other outcomes examined included: postoperative mechanical support, arrhythmia, stroke, dialysis and cardiac function. RESULTS Included for analysis were 173 patients (115 male) with median age of 63.8 (interquartile range 53.9–73.1). Major comorbidities included diabetes (45), cerebrovascular disease (34), hypertension (131), atrial fibrillation (52) and previous cardiac surgery (83). There were 108 patients (62%) who received FD re-dosing, while 65 (38%) received dilute. A greater proportion of patients in the dilute group received retrograde delivery, for both induction (32/108 vs 39/65, P CONCLUSIONS Del Nido cardioplegia has been used in complex cardiac surgery requiring prolonged cross-clamp. Re-dosing can be performed with either FD or dilute del Nido solution with no statistical difference in outcomes.

Objective To assess the clinical features and infectivity of variant B.1.1.7 among healthy young adults in a military setting. Materials and Methods Positive cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a single military base (March 23, 2020 and February 16, 2021) were included. An epidemiological investigation conducted via phone included questions regarding symptoms, exposure history, smoking status, list of contacts, and recently visited places. Symptoms surveyed included fever, cough, shortness of breath, sore throat, loss of smell or taste, gastrointestinal symptoms (GI), headache, chest pain, and constitutional symptoms. Cases were divided before B.1.1.7 first reported case in Israel (December 23, 2020) (period 1) and after its identification (period 2). Symptom distribution and the risk of a contact to be infected were compared between the periods, using a chi-square test, and a negative binominal regression model, respectively. Results Of 293 confirmed cases, 89 were reported in the first period and 204 in the second. 56.0% were men with a median age of 19.5 years (interquartile range 18.6-20.5). GI symptoms, loss of taste or smell, headache, fever, and chills were more prevalent in the first period (P Conclusion An outbreak of SARS-CoV-2 in young healthy adults, during a period with high national-wide B.1.1.7 variant prevalence, is characterized by decreased prevalence of fever, loss of taste or smell and GI symptoms, increased reports of fatigue, and more infected contacts for each index case.

OBJECTIVES Left ventricular outflow tract obstruction (LVOTO) is a recognized complication after complete repair of atrioventricular septal defect (AVSD). This study reviewed the incidence and management of LVOTO following AVSD repair at a single institution. METHODS From 1975 to 2019, 24 patients (3.3%, 24/730) underwent reoperation due to LVOTO following partial AVSD (pAVSD) and complete AVSD (cAVSD) repair. The data were retrospectively reviewed. RESULTS The incidence of LVOTO following pAVSD and cAVSD repair was 4.4% (12/275) and 2.6% (12/455). Freedom from LVOTO reoperation following pAVSD and cAVSD repair at 25 years was 94.3% [95% confidence interval (CI); 89.7–96.7] and 95% (95% CI; 91.1–97.3). The median time from complete repair of pAVSD and cAVSD to LVOTO reoperation was 4.4 years [interquartile range (IQR): 3.4–6.7] and 2.6 years (IQR: 2.2–4.7). Freedom from second LVOTO reoperation at 5, 10 and 15 years was 83.7% (95% CI; 57.2–98.2), 59.2% (95% CI; 28.7, 80.3) and 39.5% (95% CI; 13.2–65.3). The median time between the first and the second LVOTO reoperation in the groups of pAVSD and cAVSD was 6.1 years (IQR: 3.4–8.9) and 8.6 years (IQR: 5.7–9.8). There was no significant difference regarding the first (P = 0.7406) and subsequent LVOTO (P = 0.7153) following complete repair of pAVSD and cAVSD. Combined access to the left ventricular outflow tract was not protective regarding LVOTO reoccurrence. Survival for both groups after LVOTO reoperation at 15 years was 95.6% (95% CI 99.4–72.9). CONCLUSIONS Incidence of LVOTO after AVSD repair is low but the reoccurrence rate is high. Standard subaortic resection does not always provide definitive LVOTO relief. The survival after LVOTO reoperation is excellent.

Background Objective tracking of asthma medication use and exposure in real-time and space has not been feasible previously. Exposure assessments have typically been tied to residential locations, which ignore exposure within patterns of daily activities. Methods We investigated the associations of exposure to multiple air pollutants, derived from nearest air quality monitors, with space-time asthma rescue inhaler use captured by digital sensors, in Jefferson County, Kentucky. A generalized linear mixed model, capable of accounting for repeated measures, over-dispersion and excessive zeros, was used in our analysis. A secondary analysis was done through the random forest machine learning technique. Results The 1039 participants enrolled were 63.4% female, 77.3% adult (>18) and 46.8% White. Digital sensors monitored the time and location of over 286 980 asthma rescue medication uses and associated air pollution exposures over 193 697 patient-days, creating a rich spatiotemporal dataset of over 10 905 240 data elements. In the generalized linear mixed model, an interquartile range (IQR) increase in pollutant exposure was associated with a mean rescue medication use increase per person per day of 0.201 [95% confidence interval (CI): 0.189-0.214], 0.153 (95% CI: 0.136-0.171), 0.131 (95% CI: 0.115-0.147) and 0.113 (95% CI: 0.097-0.129), for sulphur dioxide (SO2), nitrogen dioxide (NO2), fine particulate matter (PM2.5) and ozone (O3), respectively. Similar effect sizes were identified with the random forest model. Time-lagged exposure effects of 0–3 days were observed. Conclusions Daily exposure to multiple pollutants was associated with increases in daily asthma rescue medication use for same day and lagged exposures up to 3 days. Associations were consistent when evaluated with the random forest modelling approach.

Background Neurotensin, a neuropeptide with direct cardiac effects, has been associated with prospective risk of hypertension-related conditions through measurement of its precursor, pro-neurotensin/neuromedin N (pro-NT/NMN). Its association with incident hypertension has not been evaluated. Methods From 2003 to 2007, the REasons for Geographic And Racial Differences in Stroke (REGARDS) study enrolled 30,239 Black or White adults age ≥45. Pro-NT/NMN was measured in 1,692 participants without baseline hypertension (self-reported antihypertensive use or blood pressure ≥140/90 mm Hg) who underwent follow-up assessment in 2013–2016. A sensitivity analysis was conducted using a lower threshold (≥130/80 mm Hg) to define hypertension. Three robust Poisson regression models were fitted to risk of incident hypertension, adding demographics, cardiometabolic risk factors, and dietary covariates. Results Six hundred and fourteen participants developed hypertension over 9.4 years of follow-up. Pro-NT/NMN ranged from 14 to 1,246 pmol/l, with median [interquartile range] 154 [112, 206] pmol/l. Pro-NT/NMN was not associated with hypertension overall (fully adjusted incidence rate ratio per SD increment log pro-NT/NMN 1.03, 95% confidence interval 0.95–1.11). Results of sensitivity analysis did not differ substantially. Conclusions Baseline pro-NT/NMN was not associated with incident hypertension. This may be a result of neurotensin’s long-term interactions with other molecular regulators of blood pressure, such as the renin–angiotensin–aldosterone system.

OBJECTIVES Abnormal invasive exercise haemodynamics in asymptomatic patients with severe mitral regurgitation were associated with higher regurgitation burden. We analysed the association between parameters of invasive exercise testing with mortality and valve surgery compared to guideline defined non-invasive criteria. METHODS This single centre, retrospective cohort study assesses the association of invasive exercise haemodynamics and mortality with and without surgery in patients with severe mitral regurgitation and normal ejection fraction (≥55%) as primary outcome. The secondary outcome was the need for mitral valve surgery in 113 asymptomatic patients primarily managed conservatively. RESULTS We identified 314 patients [age 59 years (standard deviation 13), 27% female] with available exercise haemodynamics with a median follow-up of 8.2 (interquartile range 5.2–11.2) years. Five-year survival rate was 93.0%. Pulmonary capillary wedge pressure at maximum exercise >30 mmHg was the only parameter independently associated with mortality after adjustment for age and guideline criteria [hazard ratio (HR) 2.7 (1.3–5.6), P = 0.007]. In the 113 patients primarily managed conservatively, maximum pulmonary capillary wedge pressure was independently associated with mitral valve surgery during follow-up in multivariable analysis (HR 2.10 (1.32–3.34), P = 0.002; after adjustment for workload and weight: HR 1.31 (1.14–1.52), P 25 mmHg improved the predictive power of current guideline criteria for surgery (area under the curve 0.61–0.68, P = 0.02). CONCLUSIONS Invasive exercise haemodynamics predict mortality and improve prognostic information about surgery during follow-up derived from current guideline criteria in asymptomatic patients with severe mitral regurgitation.

Aims Left atrial (LA) function assessed by two-dimensional speckle-tracking echocardiography has shown increasing clinical and prognostic significance. We sought to establish age- and sex-based normative values of LA strain in the general population and to assess the prognostic yield of lower limits of normality of LA strain in relation to future atrial fibrillation (AF). Methods and results We determined normative values of peak atrial longitudinal strain (PALS), peak atrial contraction strain (PACS), and LA strain during the conduit phase (LACS) in 1641 healthy participants included in the fifth Copenhagen City Heart Study. In a secondary analysis, a validation cohort of 2016 participants, regardless of health status, were included to assess the prognostic value of the established reference values. In the healthy cohort, median age was 46 years (interquartile range 32–57), 62% were female. Median PALS, PACS, and LACS and corresponding limits of normality in the healthy participants were 39.4% (23.0–67.6%), 15.5% (6.4–28.0%), and 23.7% (8.8–44.8%), respectively. There was a tendency of lower values of PALS and LACS in males and older participants, while PACS tended to increase with advancing age. The established lower limits of normality showed high specificity (range 93–94%) regarding future AF, implying a low risk of developing AF in participants with LA strain above the lower limits of normality in their respective sex and age group. Conclusion We report normal values for LA strain stratified by sex and age. The lower limits of normality showed high specificity regarding future AF.

Background Risk of invasive meningococcal disease (IMD) is increased in patients with complement deficiency and human immunodeficiency virus (HIV) infection. Risk associated with comorbidity is not well described. Methods This was a nationwide adult case-control study. Cases for the period 1977–2018 were identified by the national meningococcus reference laboratory. Matched controls were identified by registry linkage. Comorbidities diagnosed prior to IMD were based on the International Classification of Diseases, Eighth or Tenth Revision. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated by logistic regression after adjustment for sex, age, and other comorbidities. Results We identified 1221 cases (45% male), with a median age of 45 years (interquartile range, 22–64 years). The dominant meningococcal serogroups were B (n = 738) and C (n = 337). Increased risk of IMD was associated with solid organ transplantation (SOT) (OR 40.47 [95% CI: 4.84–337.23]), hemolytic anemia (OR 7.56 [95% CI: 2.63–21.79]), renal disease (OR 2.95 [95% CI: 1.77–4.92]), liver disease (OR 2.54 [95% CI: 1.58–4.08]), cancer (OR 2.31 [95% CI: 1.85–2.89]), diabetes (OR 1.74 [95% CI: 1.27–2.39]), neurological disease (OR 1.72 [95% CI: 1.20–2.46]), and autoimmune disease (OR 1.70 [95% CI: 1.63–2.11]). Having 1, 2, and ≥3 comorbidities was associated with increased risk of IMD (ORs 1.6–3.5). Increased risk was not associated with specific serogroups. Conclusions This study of adults with IMD over 4 decades showed increased risk of IMD associated with renal disease, immunological disorders, liver disease, cancer, and SOT ranging from a 2- to 40-fold increased risk. Vaccination may be warranted in these populations.

Background Breast cancer is the most common cancer among women worldwide and the second leading cause of brain metastases (BrM). We assessed the treatment patterns and outcomes of women treated for breast cancer BrM at our institution in the modern era of stereotactic radiosurgery (SRS). Materials and Methods We conducted a retrospective analysis of women (≥18 years of age) with metastatic breast cancer who were treated with surgery, whole brain radiotherapy (WBRT), or SRS to the brain at the Sunnybrook Odette Cancer Centre, Toronto, Canada, between 2008 and 2018. Patients with a history of other malignancies and those with an uncertain date of diagnosis of BrM were excluded. Descriptive statistics were generated and survival analyses were performed with subgroup analyses by breast cancer subtype. Results Among 683 eligible patients, 153 (22.4%) had triple-negative breast cancer, 188 (27.5%) had HER2+, 246 (36.0%) had hormone receptor (HR)+/HER2−, and 61 (13.3%) had breast cancer of an unknown subtype. The majority of patients received first-line WBRT (n = 459, 67.2%) or SRS (n = 126, 18.4%). The median brain-specific progression-free survival and median overall survival (OS) were 4.1 months (interquartile range [IQR] 1.0–9.6 months) and 5.1 months (IQR 2.0–11.7 months) in the overall patent population, respectively. Age >60 years, presence of neurological symptoms at BrM diagnosis, first-line WBRT, and HER2− subtype were independently prognostic for shorter OS. Conclusion Despite the use of SRS, outcomes among patients with breast cancer BrM remain poor. Strategies for early detection of BrM and central nervous system–active systemic therapies warrant further investigation. Implications for Practice Although triple-negative breast cancer and HER2+ breast cancer have a predilection for metastasis to the central nervous system (CNS), patients with hormone receptor–positive/HER2− breast cancer represent a high proportion of patients with breast cancer brain metastases (BrM). Hence, clinical trials should include patients with BrM and evaluate CNS-specific activity of novel systemic therapies when feasible, irrespective of breast cancer subtype. In addition, given that symptomatic BrM are associated with shorter survival, this study suggests that screening programs for the early detection and treatment of breast cancer BrM warrant further investigation in an era of minimally toxic stereotactic radiosurgery.

Background Our hypothesis was that exposure to fine particulate matter (PM2.5) is related to abnormal cord insertion, which is categorized as a form of placental implantation abnormality. We investigated the association between exposure to total PM2.5 and its chemical components over the first trimester and abnormal cord insertion, which contributes to the occurrence of adverse birth outcomes. Methods From the Japan Perinatal Registry Network database, we used data on 83 708 women who delivered singleton births at 39 cooperating hospitals in 23 Tokyo wards (2013–2015). We collected PM2.5 on a filter and measured daily concentrations of carbon and ion components. Then, we calculated the average concentrations over the first trimester (0–13 weeks of gestation) for each woman. A multilevel logistic-regression model with the hospital as a random effect was used to estimate the odds ratios (ORs) of abnormal cord insertion. Results Among the 83 708 women (mean age at delivery = 33.7 years), the frequency of abnormal cord insertion was 4.5%, the median concentration [interquartile range (IQR)] of total PM2.5 was 16.1 (3.61) μg/m3 and the OR per IQR for total PM2.5 was 1.14 (95% confidence interval = 1.06–1.23). In the total PM2.5-adjusted models, total carbon, organic carbon, nitrate, ammonium and chloride were positively associated with abnormal insertion. Organic carbon was consistently, and nitrate tended to be, associated with specific types of abnormal insertion (marginal or velamentous cord insertion). Conclusions Exposure to total PM2.5 and some of its components over the first trimester increased the likelihood of abnormal cord insertion.

OBJECTIVES This study investigated the outcomes of sarcoma patients with lung metastases who underwent pulmonary metastasectomy (PM), compared to patients who underwent medical management alone. The secondary objective was to compare survival after PM between variables of interest. METHODS This was a retrospective review of 565 sarcoma patients with confirmed, isolated pulmonary metastasis identified from the Surveillance, Epidemiology and End Results database between 2010 and 2015. 1:4 propensity score matching was used to select PM and non-PM groups. The multivariable Cox proportional hazards model was used to analyse prognostic factors of disease-free survival (DFS). RESULTS Of the eligible 565 patients, 59 PM patients were matched to 202 non-PM patients in a final ratio of 3.4. After propensity matching, there were no significant differences in baseline characteristics between PM and non-PM patients. The median DFS after PM was 32 months (interquartile range 18–59), compared to 20 months (interquartile range 7–40) in patients without PM (P = 0.032). Using a multivariable Cox proportional hazards model, metastasectomy (hazard ratio 0.536, 95% confidence interval 0.33–0.85; P = 0.008) was associated with improved DFS. In a subset analysis of patients who underwent PM only, the median DFS was longer in males compared to females (P = 0.021), as well as in bone sarcoma compared to soft tissue sarcoma (P = 0.014). CONCLUSIONS For sarcoma patients with metastatic lung disease, PM appears to improve the prognosis compared to medical management. Furthermore, there may be a survival association with gender and tumour origin in patients who underwent PM. These data may be used to inform the surgical indications and eligibility criteria for metastasectomy in this setting., Sarcomas are a heterogeneous tumour group that accounts for 1% of adult malignancies [1].

Objectives To investigate the prognostic impact of tumor burden in patients receiving nivolumab plus ipilimumab as first-line therapy for previously untreated metastatic renal cell carcinoma (mRCC). Methods We retrospectively evaluated 62 patients with IMDC intermediate- or poor-risk mRCC, treated with nivolumab plus ipilimumab as first-line therapy at five affiliated institutions. Tumor burden was defined as the sum of diameters of baseline targeted lesions according to the RECIST version.1.1. We categorized the patients into two groups based on the median value of tumor burden (i.e., high vs. low). The association of tumor burden with progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) with nivolumab plus ipilimumab treatment was analyzed. Results The median tumor burden was 63.0 cm (interquartile range: 34.2–125.8). PFS was significantly shorter in patients with high tumor burden (n = 31) than in those with low tumor burden (n = 31) (median: 6.08 [95% CI: 2.73–9.70] vs. 12.5 [4.77–24.0] months, P = 0.0134). In addition, OS tended to be shorter in patients with high tumor burden; however, there was no statistically significant difference (1-year rate: 77.3 vs. 96.7%, P = 0.166). ORR was not significantly different between patients with high and low tumor burden (35 vs. 55%, P = 0.202). Multivariate analysis of PFS further showed that tumor burden was an independent factor (HR: 2.22 [95% CI: 1.11–4.45], P = 0.0242). Conclusions Tumor burden might be a useful factor for outcome prediction, at least for PFS prediction, in patients receiving nivolumab plus ipilimumab for mRCC. Further prospective studies are warranted to confirm our findings.

Background Despite major efforts to address psychological distress and quality of life (QOL) in people with cancer, only none to small intervention effect has been observed. There is reason to question whether psychosocial needs of patients have already been met under the usual oncology care. Purpose The purpose of this systematic review was to examine changes in depression, anxiety and QOL during the existential plight in advanced cancer. Methods A literature search was performed in the PubMed and APA PsycINFO databases from year 1976 up to May 31, 2021. Longitudinal observational or experimental research targeting depression, anxiety or QOL in advanced cancer (stage III or IV), with baseline time since cancer diagnosis within 100 days, follow-up within 16 weeks post-baseline were eligible. Quality rating was based on the GRADE guidelines. Results Overall QOL did not reveal clinically relevant changes for the majority of studies as evaluated by effect size and raw score changes (median effect size 0.01, interquartile range −0.10–0.15). Nonetheless, modest to moderate improvement was found for depression (median effect size 0.28, interquartile range 0.03–0.38) and anxiety (median effect size 0.57, interquartile range 0.32–0.79). Conclusion Transient distress symptoms and temporarily reduced functioning in the oncology setting may be considered normal, whereas impaired overall QOL needs to be addressed. Developing innovative interventions that enhance QOL for patients newly diagnosed with advanced cancer without interfering with patients’ natural adaptation process is imperative.

Background Previous studies have reported mixed results regarding the contributions of cardiovascular disease (CVD) and blood pressure (BP) to cognitive impairment in chronic kidney disease. Methods This was a cross-sectional study in 1213 patients on maintenance hemodialysis from 17 dialysis units in Japan. The main exposures were prior CVD and BP components including systolic BP (SBP) and diastolic BP (DBP). The outcome was low cognitive function evaluated with the Modified Mini-Mental State (3MS) examination with a cut-off level of 3MS Results The median age was 67 years, median duration of dialysis was 71 months, 37% were women, 39% had diabetic kidney disease and 36% had any pre-existing CVD. Median (interquartile range) of 3MS score was 91 (82–97), and 240 patients (20%) had 3MS Conclusions Prior stroke and lower DBP were associated with 3MS

Background Although burnout levels in oncologists are likely high, its predictors remain poorly understood. Aims This study was aimed to verify the prevalence of occupational burnout in oncology doctors and nurses in the major cancer centre in Kazakhstan and to elucidate its predictors to plan future prevention activities. Methods In the leading tertiary-level cancer centre in Kazakhstan, we recruited 256 subjects (67% doctors and 33% nurses, 62% women, median age 37.5 [interquartile range 15] years) and offered them Maslach Burnout Inventory to quantify emotional exhaustion (EE), depersonalization (DP) and personal accomplishment (PA). Demographics, fatigue, health-related quality of life with SF-8 and lifestyle were tested as predictors of burnout in multivariate logistic regression models. Results Number of subjects with high EE was 121 (47%), high DP was 161 (63%) and high PA was 152 (59%). Fatigue, worse mental component score (MCS), being single and not exercising regularly predicted more burnout in EE. Fatigue, worse physical component score (PCS) and worse MCS predicted more burnout in DP. Finally, more burnout in PA was independently associated with fatigue, worse PCS, being married or divorced and having a university or academic degree. Conclusions The prevalence of occupational burnout in oncologists was high, necessitating early burnout prevention programmes, addressing, among other, fatigue reduction and regular exercise.

Background Lymphatic filariasis (LF) is a public health problem in Sabah, Malaysia. In the subdistrict of Tangkarason, nine rounds of mass drug administration (MDA) were probably not effective in reducing the prevalence of microfilaria to the Methods Eligible adults >18 y of age in seven endemic villages in Tangkarason, Beluran, Sabah, were interviewed and tested for LF antibody using the Brugia Rapid kit. Multivariable logistic regression was employed to analyse the associated factors. Results A total of 244 respondents were included in this study. Their median age was 40 y (interquartile range 30–53). The antibody prevalence of brugian filariasis in the study population was 31.1% (95% confidence interval [CI] 25.7 to 37.2). Older age (adjusted odds ratio [aOR] 1.04 [95% CI 1.02 to 1.06]) and outdoor jobs (aOR 2.26 [95% CI 1.05 to 4.85]) were identified as independent risk factors for positive LF antibody. Participating in the MDA program previously (aOR 0.24 [95% CI 0.10 to 0.57]) was found to be a protective factor for LF infection. Conclusions A high prevalence of microfilariae was confirmed in all the study sites, which was above the target of

Aim The aim of this study was to assess the prognostic value of ABCDE-SE in a prospective, large scale, multicentre, international, effectiveness study. Stress echocardiography (SE) was recently upgraded to the ABCDE protocol: step A, regional wall motion abnormalities; step B, B lines; step C, left ventricular contractile reserve; step D, Doppler-based coronary flow velocity reserve in left anterior descending coronary artery; and step E, electrocardiogram-based heart rate reserve. Methods and results From July 2016 to November 2020, we enrolled 3574 all-comers (age 65 ± 11 years, 2070 males, 58%; ejection fraction 60 ± 10%) with known or suspected chronic coronary syndromes referred from 13 certified laboratories. All patients underwent clinically indicated ABCDE-SE. The employed stress modality was exercise (n = 952, with semi-supine bike, n = 887, or treadmill, n = 65 with adenosine for step D) or pharmacological stress (n = 2622, with vasodilator, n = 2151; or dobutamine, n = 471). SE response ranged from score 0 (all steps normal) to score 5 (all steps abnormal). All-cause death was the only endpoint. Rate of abnormal results was 16% for A, 30% for B, 36% for C, 28% for D, and 37% for E steps. During a median follow-up of 21 months (interquartile range: 13–36), 73 deaths occurred. Global X2 was 49.5 considering clinical variables, 50.7 after step A only (P = NS (not significant)) and 80.6 after B–E steps (P, Graphical Abstract This study recruited 3,574 patients from 13 stress echo laboratories of 5 countries and shows the prognostic value of the new state-of-the art cardiac functional testing with stress echo ABCDE protocol: Step A for regional wall motion abnormalities; step B for B-lines obtained with 4-site simplified scan and lung ultrasound; step C for contractile reserve with volumetric echocardiography; step D for Doppler-based assessment of coronary flow reserve in mid-distal left anterior descending coronary artery; step E for EKG-based heart rate reserve.

Background Vaccination is the primary strategy to reduce influenza burden. Influenza vaccine effectiveness (VE) can vary annually depending on circulating strains. Methods We used a test-negative case-control study design to estimate influenza VE against laboratory-confirmed influenza-related hospitalizations among children (aged 6 months–17 years) across 5 influenza seasons in Atlanta, Georgia, from 2012–2013 to 2016–2017. Influenza-positive cases were randomly matched to test-negative controls based on age and influenza season in a 1:1 ratio. We used logistic regression models to compare odds ratios (ORs) of vaccination in cases to controls. We calculated VE as [100% × (1 – adjusted OR)] and computed 95% confidence intervals (CIs) around the estimates. Results We identified 14 596 hospitalizations of children who were tested for influenza using the multiplex respiratory molecular panel; influenza infection was detected in 1017 (7.0%). After exclusions, we included 512 influenza-positive cases and 512 influenza-negative controls. The median age was 5.9 years (interquartile range, 2.7–10.3), 497 (48.5%) were female, 567 (55.4%) were non-Hispanic Black, and 654 (63.9%) children were unvaccinated. Influenza A accounted for 370 (72.3%) of 512 cases and predominated during all 5 seasons. The adjusted VE against influenza-related hospitalizations during 2012–2013 to 2016–2017 was 51.3% (95% CI, 34.8% to 63.6%) and varied by season. Influenza VE was 54.7% (95% CI, 37.4% to 67.3%) for influenza A and 37.1% (95% CI, 2.3% to 59.5%) for influenza B. Conclusions Influenza vaccination decreased the risk of influenza-related pediatric hospitalizations by >50% across 5 influenza seasons.

Introduction The coronavirus-2019 (COVID-19) pandemic has significantly impacted global healthcare delivery. Brooke Army Medical Center (BAMC) is the DoD’s largest hospital and a critical platform for maintaining a ready medical force. We compare temporal trends in patient volumes and characteristics in the BAMC emergency department (ED) before versus during the pandemic. Materials and Methods We abstracted data on patient visits from the BAMC ED electronic medical record system. Data included patient demographics, visit dates, emergency severity index triage level, and disposition. We visually compared the data from January 1, 2019 to November 30, 2019 versus January 1, 2020 to November 30, 2020 to assess the period with the most apparent differences. We then used descriptive statistics to characterize the pre-pandemic control period (1 March-November 30, 2019) versus the pandemic period (1 March-November 30, 2020). Results Overall, when comparing the pre-pandemic and pandemic periods, the median number of visits per day was 232 (Interquartile Range (IQR) 214-250, range 145-293) versus 165 (144-193, range 89-308, P Conclusions The BAMC ED experienced a significant decrease in patient volume during the COVID-19 pandemic starting in March 2020. This may have significant implications for the capacity of this facility to maintain a medically ready force.

BACKGROUND Brentuximab vedotin (BV) was approved as a therapy for mycosis fungoides (MF) based on the ALCANZA trial. Little real-world data, however, are available. OBJECTIVES To evaluate the efficacy and safety of BV in patients with MF/Sezary Syndrome (SS) with variable CD30 positivity in a real-world cohort and to explore potential predictors of response. METHODS Data from 72 patients with MF/SS across nine EORTC (European Organization for Research and Treatment of Cancer) centres were included. The primary endpoint was to evaluate the proportion of patients with: overall response (ORR), ORR lasting over 4 months (ORR4), time to response (TTR), response duration (RD), progression-free survival (PFS) and time to next treatment (TTNT). Secondary aims included a safety evaluation and the association of clinicopathological features with ORR, RD and TTNT. RESULTS All 72 patients had received at least one systemic treatment. ORR was achieved in 45 of 67; ORR4 in 28 of 67 with a median TTR of 8 weeks [interquartile range (IQR) 5·5-14] and with a median RD of 9 months (IQR 3·4-14). Median PFS was 7 months (IQR 2-12) and median TTNT was 30 days (6-157·5). Patient response, RD, PFS and TTNT were not associated with any clinicopathological characteristics. In the MF group, patients with stage IIB/III vs. IV achieved longer PFS and had a higher percentage of ORR4. There was a statistically significant association between large-cell transformation and skin ORR (P = 0·03). ORR4 was more frequently achieved in patients without lymph node involvement (P = 0·04). CONCLUSIONS BV is an effective option for patients with MF/SS, including those with variable CD30 positivity, large-cell transformation, SS, longer disease duration and who have been treated previously with several therapies.

OBJECTIVES The aim of this study was to evaluate the short- to mid-term outcomes of descending thoracic aortic aneurysm (DTAA) repair from the Gore Global Registry for Endovascular Aortic Treatment (GREAT). METHODS This is a multicentre sponsored prospective observational cohort registry. The study population comprised those treated for DTAA receiving GORE thoracic aortic devices for DTAA repair between August 2010 and October 2016. Major primary outcomes were early and late survival, freedom from aorta-related mortality and freedom from aorta-related reintervention. RESULTS There were 180 (58.1%) males and 130 (41.9%) females: the mean age was 70 ± 11 years (range 18–92). The median maximum DTAA diameter was 60 mm (interquartile range 54–68.8). Technical success was achieved in all patients. Operative mortality, as well as immediate conversion to open repair, was never observed. At the 30-day window, mortality occurred in 4 (1.3%) patients, neurological events occurred in 4 (1.3%) patients (transient ischaemic attacks/stroke n = 3, paraplegia n = 1) and the reintervention rate was 4.5% (n = 14). Estimated survival was 95.6% [95% confidence interval (CI) 92.6–97.4] at 6 months, 92.7% (95% CI 89.1–95.2) at 1 year and 57.3% (95% CI 48.5–65.1) at 5 years. Freedom from aorta-related mortality was 98.3% (95% CI 96.1–99.3) at 6 months, 98.3% (95% CI 96.1–99.3) at 1 year and 92.2% (95% CI 83.4–96.4) at 5 years. Freedom from thoracic endovascular aortic repair (TEVAR)-related reintervention at 5 years was 87.2% (95% CI 81.2–91.4). CONCLUSIONS TEVAR for DTAAs using GORE thoracic aortic devices is associated with a low rate of device-related reinterventions and is effective at preventing aorta-related mortality for up to 5 years of follow-up. Clinical registration number NCT number: NCT01658787. Subject collection 161, 164.

The purpose of this study was to determine whether circular RNA hsa_circ_0002874 could serve as a novel biomarker for the diagnosis of gastric cancer (GC). The expression level of hsa_circ_0002874 mean (interquartile range [IQR]) in the plasma of patients with GC, patients with benign gastric lesions, and healthy individuals was 3.482 (IQR, 1.524–9.048), 1.261 (IQR, 0.817–2.000), and 1.00 (IQR, 0.726–1.382), respectively, whereas there was no significant difference between the latter 2 groups. The plasma expression level of hsa_circ_0002874 was significantly correlated with tumor stage (U = 234.0; P

AimsDesmoplakin (DSP) cardiomyopathy is an increasingly recognized form of arrhythmogenic cardiomyopathy. With a genotype-specific approach, we characterized the diagnosis, natural history, and risk for ventricular arrhythmia and heart failure in DSP cardiomyopathy.Methods and resultsWe followed 91 individuals [45 probands, 34% male, median age 27.5 years (interquartile interval 20.0–43.9)] with pathogenic or likely pathogenic DSP variants for a median of 4.3 years. Regarding the ventricular involvement, left predominance was most common (n = 22, 28%) followed by bi-ventricular in 12 (15%) and right predominance in 5 (6%). Myocardial injury (chest pain, elevated troponin, normal coronary angiogram) occurred in 20 (22%) individuals. Incidence rates of sustained ventricular arrhythmia and heart failure (ventricular dysfunction ± symptoms) were 5.9 [95% confidence interval (CI): 3.9–9.1] and 6.7 (95% CI: 4.5–9.8) per 100 person-years, respectively. In univariate regression, myocardial injury was associated with sustained ventricular arrhythmia [hazard ratio (HR) 2.53, 95% CI: 1.05–6.11] and heart failure (HR 7.53, 95% CI: 3.10–18.26). After adjustment, left ventricular ejection fraction ConclusionDSP cardiomyopathy affects both ventricles and carries high risk for ventricular arrhythmia and heart failure. Myocardial injury is associated with worse disease outcomes. Both diagnosis and risk stratification of DSP cardiomyopathy need refinement.

OBJECTIVES The aim of this study was to evaluate technical/clinical outcomes of the Gore TAG Conformable Thoracic Stent Graft with Active Control System (CTAG with ACS) in thoracic aortic disease since its introduction in Europe in 2017. METHODS Patients undergoing thoracic endovascular aortic repair (TEVAR) with the device between 2017 and 2020 were identified from a prospectively maintained single-centre database and retrospectively analysed. Predominant indications were aortic dissection (n = 46), thoracic/thoraco-abdominal aneurysm (n = 20/n = 7), penetrating ulcer (n = 14) and intramural haematoma (n = 12). Emergency procedures were performed in 47% (54/115). The primary outcome was technical success. Secondary outcomes were clinical success, serious adverse events and procedure-related reintervention. ACS was assessed regarding angulation, accuracy and apposition. The median follow-up was 8.46 months (interquartile range: 3.18–16.89 months). RESULTS A total of 115 consecutive patients (82 males, median age 63; interquartile range: 53–74 years) have been included. Technical success was achieved in 95.7% (110/115). Clinical success rate was 80.9% (93/115); mostly due to procedure-related death (n = 14). Overall mortality was 19.1% (22/115), with significant differences between elective/emergency procedures (log-rank: P CONCLUSIONS This single-centre study shows encouraging performance of the CTAG with ACS in an array of aortic pathologies. Although longer-term data must be awaited, ACS leads to overall favourable device placement. Despite ongoing advances in device technology, TEVAR remains challenging and is associated with significant burden inherent to the underlying disease.

Summary Background A prediction interval represents a clinical interpretation of heterogeneity. The aim of this study was to determine the prevalence of prediction interval reporting in orthodontic random effect meta-analyses. The corroboration between effect size estimates with 95% confidence intervals (CIs) and prediction intervals were also explored. Materials and methods Systematic reviews (SRs) published between 1 January 2010 and 31 January 2021 containing at least one random effects meta-analysis (minimum of three trials) were identified electronically. SR and meta-analyses characteristics were extracted and prediction intervals, where possible, were calculated. Descriptive statistics and the percentage of meta-analyses where the prediction interval changed the interpretation based on the 95% CI were calculated. Fisher’s exact test was used to examine associations between the study variables and reporting of prediction intervals. Results One hundred and twenty-one SRs were included. The median number of SR authors was 5 (interquartile range: 4–6). The reporting of prediction intervals was undertaken in only 19.0% (N = 23/121) of meta-analyses. Out of 95 meta-analyses, only in 6 (6.3%, N = 6/95) were the 95% CI corroborated by the prediction interval. In 60 meta-analyses (63.3%, N = 60/95) despite a 95% CI indicating a statistically significant result, this was not corroborated by the corresponding prediction interval. Conclusions Within the study timeframe, reporting of prediction intervals is not routinely undertaken in orthodontic meta-analyses possibly due to a lack of awareness. In future orthodontic random effects models containing a minimum of three trials, reporting of prediction intervals is advocated as this gives an indication of the range of the expected effect of treatment interventions.

Aims While myocardial ischaemia plays a major role in the pathogenesis of heart failure (HF), the indications for coronary angiography during acute HF are not established. We determined the association of early coronary angiography during acute HF hospitalization with 2-year mortality, cardiovascular death, HF readmissions, and coronary revascularization. Methods and results In a two-stage sampling process, we identified acute HF patients who presented to 70 emergency departments in Ontario (April 2010 to March 2013) and determined whether they underwent early coronary angiography within 14 days after presentation using administrative databases. After clinical record review, we defined a cohort with acute ischaemic HF as patients with at least one factor suggesting underlying ischaemic heart disease, including previous myocardial infarction, troponin elevation, or angina on presentation. We oversampled patients undergoing angiography. We used inverse-probability-of-treatment weighting (IPTW) to adjust for baseline differences. Of 7239 patients with acute HF, 2994 met inclusion criteria [median age 75 (interquartile range 65–83) years; 40.9% women]. Early angiography was performed in 1567 patients (52.3%) and was associated with lower all-cause mortality [hazard ratio (HR) 0.74, 95% confidence interval (CI) 0.61–0.90, P = 0.002], cardiovascular death (HR 0.72, 95% CI 0.56–0.93, P = 0.012), and HF readmissions (HR 0.84, 95% CI 0.71–0.99, P = 0.042) after IPTW. Those undergoing early angiography experienced higher rates of percutaneous coronary intervention (HR 2.58, 95% CI 1.73–3.86, P Conclusions Early coronary angiography was associated with lower all-cause mortality, cardiovascular death, HF readmissions, and higher rates of coronary revascularization in acute HF patients with possible ischaemia.

Aims To elucidate the frequency and clinical impact of left atrial appendage thrombus (LAAT) in patients set for transcatheter aortic valve implantation (TAVI). Methods and results All patients undergoing TAVI between January 2014 and June 2020 with analysable multislice computed tomography (MSCT) for LAAT were included. Baseline and procedural characteristics were collected, pre-procedural MSCT’s were retrospectively analysed for LAAT presence. The primary endpoint was defined as the cumulative incidence of any cerebrovascular event (stroke or transient ischaemic attack) within the first year after TAVI. A Cox proportional hazards model was used to identify predictors. A total of 1050 cases had analysable MSCT. Median age was 80 [interquartile range (IQR) 74–84], median Society of Thoracic Surgeons’ Predicted Risk Of Mortality (STS-PROM) was 3.4% (IQR 2.3–5.5). Thirty-six percent were on oral anticoagulant therapy for atrial fibrillation (AF). LAAT was present in 48 (4.6%) of cases. Patients with LAAT were at higher operative risk [STS-PROM: 4.9% (2.9–7.1) vs. 3.4% (2.3–5.5), P = 0.01], had worse systolic left ventricular function [EF 52% (35–60) vs. 55% (45–65), P = 0.01] and more permanent pacemakers at baseline (35% vs. 10%, P Conclusion Patients with MSCT-identified LAAT were at higher risk for cerebrovascular events during the first year after TAVI.

Background Severe malaria can be deadly and requires treatment with intravenous artesunate (IVAS). The Centers for Disease Control and Prevention provided IVAS starting 1 April 2019 for all patients with severe malaria in the United States. This study describes the safety and effectiveness of IVAS in these patients. Methods Patients meeting criteria for severe malaria April 2019–December 2020 who received IVAS were included. Demographic, clinical, laboratory, adverse event, and outcome information were collected. Clinical presentation, time to reach 1% and 0% parasitemia, adverse events, and death were described using proportions, medians, interquartile range (IQR), and tests of significance for differences in proportions. Results Of 280 patients included, the majority were male (61.4%), Black (75.0%), with a median age of 35 years (IQR: 15.8–53.9). Most had Plasmodium falciparum (83.6%) with median parasitemia of 8.0% (IQR: 4.6–13.2). Of 170 patients with information, 159 (93.5%) reached ≤1% parasitemia by the third IVAS dose with a median time of 17.6 hours (IQR: 10.8–28.8), and 0% parasitemia in a median of 37.2 hours (IQR 27.2–55.2). Patients with parasite densities >10% and those requiring adjunct therapy had significantly higher parasite clearance times. Adverse events associated with IVAS were reported in 4.8% (n = 13 of 271). Eight patients had post-artesunate delayed hemolysis that resolved. There were 5 (1.8%) deaths, all attributable to severe malaria. Conclusions IVAS is a safe and effective drug for the treatment of severe malaria in the United States; timely administration can be lifesaving.

OBJECTIVES The use of a hybrid operating room equipped with robotic C-arm cone-beam computed tomography for single-step localization and excision of small pulmonary nodules finds high cost barriers. The new generation of 3D C-arm system not only depicts soft tissues with high contrast but also offers a more affordable and sustainable solution. This approach has been chiefly applied in the field of orthopedic surgery. In this case series, we describe the use of a mobile 3D C-arm system for localizing and removing small pulmonary nodules. METHODS Between July and September 2020, we identified 14 patients who underwent localization and removal of small pulmonary nodules with a 3D C-arm system. We retrospectively reviewed clinical records to document the feasibility and safety of the procedure. RESULTS The median tumour size was 7.5 mm [interquartile range (IQR): 5 − 9.75 mm], with a median distance from the pleural surface of 4.2 mm (IQR: 0.5 − 6.45 mm). We successfully visualized all of the pulmonary lesions by intraoperative CT imaging. Localization was achieved in 13 patients, who subsequently underwent complete thoracoscopic resection. The median time required to localize lesions was 41.5 min (IQR: 33.75 − 53.25 min), with a median radiation exposure (expressed through the skin absorbed dose) of 143.45 mGy (IQR: 86.1 − 194.6 mGy). Failure to localize occurred in 1 patient because of pneumothorax caused by repeated needle puncture. All patients were successfully discharged and the median length of stay was 2.5 days (IQR: 2 − 3 days). CONCLUSIONS This case series demonstrates the feasibility of single-step localization and excision of small pulmonary nodules using a mobile 3D C-arm.

OBJECTIVES Although video-assisted thoracic surgery (VATS) has shortened hospitalization duration for non-small-cell lung cancer (NSCLC) patients, the factors associated with early discharge remain unclear. This study aimed to identify patients eligible for a 72-h stay after VATS anatomical resection. METHODS Monocentric retrospective study including all consecutive patients undergoing VATS anatomical resection for NSCLC between February 2010 and December 2019. Two groups were defined according to the discharge: ‘early discharge’ (within 72 postoperative hours) and ‘routine discharge’ (at >72 postoperative hours). RESULTS A total of 660 patients with a median age of 66.5 years (interquartile range 60–73 years) (female/male: 321/339) underwent VATS anatomical pulmonary resection for NSCLC [segmentectomy in 169 (25.6%), lobectomy in 481 (72.9%), bilobectomy in 8 (1.2%) and pneumonectomy in 2 (0.3%) patients]. The cardiopulmonary and Clavien–Dindo III–IV postoperative complication rates were 32.6% and 7.7%, respectively. The median postoperative length of stay was 6 days (interquartile range 4–10 days). In total, 119 patients (18%) could be discharged within 72 h of surgery. On multivariable analysis, the factors significantly associated with an increased likelihood of early discharge were: body mass index >20 kg/m2 [odds ratio (OR) 2.37], absence of prior cardiopathy (OR 2), diffusing capacity of the lung for carbon monoxide >60% (OR 1.82), inclusion in an enhanced recovery after surgery protocol (OR 2.23), use of a single chest tube (OR 5.73) and postoperative transfer to the ward (OR 4.84). Factors significantly associated with a decreased likelihood of early discharge were: age >60 years (OR 0.53), American Society of Anaesthesiologists score >2 (OR 0.46) and use of an epidural catheter (OR 0.41). Readmission rates were not statistically different between both groups (5.9% vs 3.1%; P = 0.17). CONCLUSIONS Age, pulmonary functions and comorbidities may influence discharge after VATS anatomical resection. The early discharge does not increase readmission rates.

OBJECTIVES Practice patterns for the use of extracorporeal membrane oxygenation (ECMO) during high-risk airway interventions vary, and data are limited. We aim to characterize our recent experience using ECMO for procedural support during whole-lung lavage (WLL) and high-risk bronchoscopy for central airway obstruction (CAO). METHODS We performed a retrospective cohort study of adults who received ECMO during WLL and high-risk bronchoscopy from 1 July 2018 to 30 March 2020. Our primary end point was successful completion of the intervention. Secondary end points included ECMO-associated complications and hospital survival. RESULTS Eight patients received venovenous ECMO for respiratory support during 9 interventions; 3 WLLs for pulmonary alveolar proteinosis were performed in 2 patients, and 6 patients underwent 6 bronchoscopic interventions for CAO. We initiated ECMO prior to the intervention in 8 cases and during the intervention in 1 case for respiratory decompensation. All 9 interventions were successfully completed. Median ECMO duration was 17.8 h (interquartile range, 15.9–26.6) for the pulmonary alveolar proteinosis group and 1.9 h (interquartile range, 1.4–8.1) for the CAO group. There was 1 cannula-associated deep vein thrombosis; there were no other ECMO complications. Seven patients (87.5%) and 4 (50.0%) patients survived to discharge and 1 year postintervention, respectively. CONCLUSIONS Use of venovenous ECMO to facilitate high-risk airway interventions is safe and feasible. Planned preprocedural ECMO initiation may prevent avoidable respiratory emergencies and extend therapeutic airway interventions to patients otherwise considered too high-risk to treat. Guidelines are needed to inform the utilization of ECMO during high-risk bronchoscopy and other airway interventions.

Aims Little is known about the prevalence of aortic aneurysms among people living with HIV (PLWH). We investigated whether HIV status is independently associated with having aortic aneurysms. Furthermore, we determined risk factors associated with aortic aneurysms in PLWH. Methods and results PLWH aged ≥40 years (n = 594) were recruited from the Copenhagen Comorbidity in HIV Infection study and matched for age and sex with uninfected controls (n = 1188) from the Copenhagen General Population Study. Aortic dimensions were assessed using contrast enhanced computed tomography. Aortic aneurysms were defined according to the European Society of Cardiology guidelines, i.e. an aortic dilation of ≥50% or an infrarenal aortic diameter of ≥30 mm. Among PLWH and uninfected controls, the median (interquartile range) age was 52 (47–60) and 52 (48–61) and 88% and 90% were male, respectively. We found 46 aneurysms in 42 (7.1%) PLWH and 31 aneurysms in 29 (2.4%) uninfected controls (P Conclusion PLWH had four-fold higher odds of aortic aneurysms compared to uninfected controls, and HIV status was independently associated with aortic aneurysms. Among PLWH, age, obesity and hepatitis B co-infection were associated with higher odds of aortic aneurysms. Our findings suggest that increased attention to aortic aneurysms in PLWH may be beneficial.

Background Stroke survivors living in care homes require high levels of support with everyday living. The aims of this study were to describe the survival, health status and care received by stroke survivors living in care homes at 1-year post-stroke, compared with those in their own homes. Methods A total of 3,548 stroke survivors with a first ever stroke between 1998 and 2017 in the South London Stroke Register were identified for survival analysis. A total of 2,272 were included in the 1-year follow-up analysis. Cox regression and Kaplan–Meier plots were used to describe survival, stratified into four 5-year cohorts. Health status, medications and rehabilitation received at 1-year post-stroke were compared using descriptive statistics. Results Over the 20-year period, survival improved for stroke survivors discharged to their own home (P < 0.001) but not for those discharged to care homes (P = 0.75). Care home residents were highly disabled (median Barthel index: 6/20, interquartile range: 2–10). Rates of secondary stroke prevention medications at 1-year follow-up increased over time for care home residents, including antiplatelets from 12.3 to 38.1%, although still lower than for those in their own homes (56.3%). Speech and language problems were common in the care home population (40.0%), but only 16% had received speech and language therapy. Conclusions Rates of secondary stroke prevention prescribing increased over 20 years but remained lower in care home residents. The lower levels of rehabilitation received by stroke survivors in care homes, despite their higher levels of disability, suggest a gap in care and urgent need for restorative and/or preventative rehabilitation.

Background Malnutrition affects approximately 20% of older adult populations in Europe, yet their views on the condition are rarely explored. This qualitative study aimed to explore the experiences of older adults living with malnutrition and prescribed oral nutritional supplements in the community setting. Methods Semi-structured individual interviews were used to collect data from 13 community-dwelling individuals aged ≥60 years with a current or previous prescription for oral nutritional supplements. Self-perceived health status was measured using the EuroQol EQ-5D-5L, a short questionnaire and visual analogue scale. Interviews were audio-recorded and transcribed verbatim. Interview data were organized using NVivo 12 and analyzed using inductive thematic analysis. Results Median age was 80.0 (interquartile range 19.5) years, seven were male and six were female. Median health score was 60.0 (interquartile range 35.0) out of 100. Almost one-third reported severe or extreme problems with usual activities, and pain or discomfort. One main theme was identified from the interviews: ‘It takes a village’, with four subthemes (i) ‘I get by with a little help from my friends’, (ii) ‘The obvious diagnosis’, (iii) ‘The missing T in MDT’ and (iv) ‘Confusion’. Participants with malnutrition reported relying on friends, family and carers with poor multidisciplinary team communication and lack of dietetic support. Conclusions Participants in this study experienced poor management of malnutrition with missing links between the hospital and community healthcare settings, and lack of dietetic services. Patient views should be used to inform public health guidelines and guide future interventions in the community to improve the health status of older adults with malnutrition.

Background The U.S. Indo-Pacific Command (INDOPACOM) has over 375,000 military personnel, civilian employees, and their dependents. Routine pediatric care is available in theater, but pediatric subspecialty, surgical, and intensive care often require patient movement. Transfer is frequently performed by military air evacuation teams and intermittently augmented by civilian services. Pediatric care requires special training and equipment, yet most transports are staffed by non-pediatric specialists. We seek to describe the epidemiology of pediatric transport missions in INDOPACOM. Methods A retrospective review of all patients less than 18 years old transported within INDOPACOM and logged into the Transportation Command Regulating and Command and Control Evacuation System (TRAC2ES) database from June 2008 through June 2018 was conducted. Data are reported using descriptive statistics. Patients were categorized into four age groups: neonatal ( Results During the study period, 687 out of 4,217 (16.3%) transports were children. Median age was 4 years (interquartile range 6 months to 8 years) and 654 patients (95.2%) were transported via military fixed-wing aircraft. There were 219 (31.9%) neonates, 162 (23.6%) infants, 133 (19.4%) young children, and 173 (25.2%) older children. Most common diagnoses encountered were respiratory, cardiac, or abdominal, although older children had a higher percentage of psychiatric diagnoses (28%). Mechanical ventilation was used in 118 (17.2%) patients, and 75 (63.6%) of these patients were neonates. Conclusions Within TRAC2ES, nearly one in six encounters were patients aged

Background Scabies causes intense itching and skin lesions. A small number of studies have shown that scabies impacts health-related quality of life (HRQoL), but no studies have been conducted in the Pacific region. We assessed the impact of scabies on HRQoL in a high-prevalence setting using the Children's Dermatology Life Quality Index (CDLQI) and Dermatology Life Quality Index (DLQI). We also assessed the validity of these tools in a Pacific Island population. Methods The study was conducted in the Solomon Islands. Participants with and without skin disease were randomly selected. HRQoL indices were scored on a scale of 0–30. Results We surveyed 1051 adults (91 with scabies) and 604 children (103 with scabies). Scabies had a small impact on HRQoL, with a median DLQI score of 2 (interquartile range [IQR] 0–6) and a CDLQI score of 2 (IQR 0–4). Scores increased linearly with severity. The greatest impact on QoL was due to itch, sleep disturbance and impacts on education and employment. Conclusions Scabies has a small but measurable impact on HRQoL. The DLQI and CDLQI scores were discriminated between the skin-related QoL of patients with scabies and the control group, indicating that these tools are appropriate to measure skin-related QoL in the Solomon Islands.

OBJECTIVESThe short-term results of video-assisted thoracoscopic surgical ablation (VTSA) with box lesion have been highly variable, and the actual efficacy requires clarification through longer follow-ups. We aimed to report which patients might benefit more from VTSA with box lesion by longer follow-up.METHODSFrom September 2010 to November 2016, patients with atrial fibrillation (AF) who underwent VTSA with box lesion were screened. All enrolled patients visited the outpatient clinic and underwent 24-h Holter monitoring at 3, 6 and 12 months after surgery and annually thereafter.RESULTSA total of 91 consecutive patients [age, 58.0 (interquartile interval from 52.0 to 62.0) years; male, 71.4%] with paroxysmal (67%) or persistent/long-standing persistent (33%) AF were enrolled. After a median follow-up of 48 months (interquartile interval from 36 to 60 months), freedom from atrial tachyarrhythmias without antiarrhythmic drugs (AADs) was 76.5%, 66.0% and 66.0% for paroxysmal AF and 58.6%, 47.8% and 34.2% for persistent/long-standing persistent AF at 12, 36 and 60 months, respectively (P = 0.017). The preoperative left atrial diameter >40 mm (hazard ratio: 2.837, 95% confidence interval: 1.408–5.716; P = 0.004) and age >50 years (hazard ratio: 2.927, 95% confidence interval: 1.359–6.305; P = 0.006) were associated with recurrences of atrial tachyarrhythmias. In patients with paroxysmal AF and left atrial diameter ≤40 mm (n = 43), freedom from atrial tachyarrhythmias without AADs was 81.4%, 74.3% and 74.3% at 12, 36 and 60 months, respectively.CONCLUSIONSIn patients with paroxysmal AF and left atrial diameter ≤40 mm, 5-year freedom from atrial tachyarrhythmias without AADs was 74.3%, which was better than that in patients with left atrial diameter >40 mm. A larger sample size and improved study design are needed to confirm our conclusions.

Aims Circulating progenitor cells (CPCs) play a role in vascular repair and plaque stability, while osteocalcin (OC) expressing CPCs have been linked to unstable plaque and adverse cardiovascular outcomes. However, their role in cardiac allograft vasculopathy (CAV) has not been elucidated. This cohort study aimed to investigate the contribution of CPCs on CAV progression and cardiovascular events after heart transplantation. Methods and results A total of 80 heart transplant patients (mean age 55 ± 14 years, 72% male) undergoing annual intravascular ultrasound (IVUS) had fresh CPCs marked by CD34, CD133, and OC counted in peripheral blood using flow cytometry, on the same day as baseline IVUS. CAV progression was assessed by IVUS as the change (Δ) in plaque volume divided by segment length (PV/SL), adjusted for the time between IVUS measurements (median 3.0, interquartile range (IQR) [2.8, 3.1] years), and was defined as ΔPV/SL that is above the median ΔPV/SL of study population. Major adverse cardiac events (MACE) was defined as any incident of revascularization, myocardial infarction, heart failure admission, re-transplantation, stroke and death. Patients with higher CD34+CD133+ CPCs had a decreased risk of CAV progression (odds ratio 0.58, 95% confidence interval [CI] [0.37, 0.92], p = 0.01) and MACE (hazard ratio [HR] 0.79, 95% CI [0.66, 0.99], p = 0.05) during a median (IQR) follow up of 8.0 years (7.2, 8.3). Contrarily, higher OC+ cell counts were associated with an increased risk of MACE (HR 1.26, 95% CI [1.03, 1.57], p = 0.02). Conclusions Lower levels of CD34+CD133+ CPCs are associated with plaque progression and adverse long-term outcomes in patients who underwent allograft heart transplantation. In contrast, higher circulating OC+ levels are associated with adverse long term outcomes. Thus, CPCs might play a role in amelioration of transplant vasculopathy, while OC expression by these cells might play a role in progression. Translational perspective The results of the current study suggest lower levels of circulating CD34+CD133+ cell levels are associated with cardiac allograft vasculopathy progression and future adverse cardiovascular events, while higher OC+ cell levels are associated with a greater risk of future cardiovascular events. Further studies confirming our findings might elucidate the role of circulating progenitor cells in the pathophysiology of CAV. Moreover, our findings might support the use of circulating progenitors as biomarkers, as well as the notion of cell therapy as potential treatment option for CAV, a disease with severe burden and limited treatment options.

Background: Although experimental results showed that epicutaneous exposure of urban ambient air pollution induces skin inflammation, its clinical relevance in the real-world setting has not been thoroughly examined yet. Objectives: This study investigated the short-term effect of ambient air pollution on the risk of hospital outpatient visits for eczematous skin disorders in seven metropolitan cities of South Korea. Methods: We conducted a time-stratified case-crossover study. Hourly mean concentrations of air pollutants(PM10, PM2.5, SO2, NO2) and meteorological data were obtained from the Ministry of Environment. The percent increase in the risk of outpatient visits associated with an interquartile range increase in particulate matters was determined by conditional logistic regression analysis after adjusting for national holidays and meteorological factors. Results: Among the types of air pollutants, both PM10 and SO2 were most significantly associated with an increased risk of outpatient visits for eczematous dermatitis. The effect of air pollutants on the outpatient visits was largely confined between lag 0 to 4. Cumulative lag analysis showed a gradual increase in outpatient visits by PM10 and SO2. Sensitivity analysis demonstrated significantly increased cumulative risks for atopic dermatitis, allergic contact dermatitis, and irritant dermatitis during lag 0-4. Conclusion: Our results suggest that ambient air pollution increases the risk of outpatient visits for eczematous skin diseases

Introduction Frailty is a disorder of multiple physiological systems impairing the capacity of the organism to cope with insult or stress. It is associated with poor outcomes after acute illness. Our aim was to study the impact of frailty on the functional outcome of patients with acute ischemic stroke (AIS) submitted to endovascular stroke treatment (EST). Methods We performed a retrospective study of patients with AIS of the anterior circulation submitted to EST between 2012 and 2017, based on a prospectively collected local registry of consecutive patients. The Hospital Frailty Risk Score (HFRS) at discharge was calculated for each patient. We compared groups of patients with and without favourable 3-month outcome after index AIS (modified Rankin Scale 0–2 and 3–6, respectively). A multivariable logistic regression model was used to identify variables independently associated with favourable 3-month outcome. Diagnostic test statistics were used to compare HFRS with other prognostic scores for AIS. Results We included 489 patients with median age 75.6 years (interquartile range [IQR] = 65.3–82.3) and median NIHSS 15 (IQR = 11–19). About 29.7% presented a high frailty risk (HFRS >15 points). Patients with favourable 3-month outcome presented lower HFRS and lower prevalence of high frailty risk. High frailty risk was independently associated with decreased likelihood of favourable 3-month outcome (adjusted odds ratio = 0.48, 95% confidence interval = 0.26–0.89). Diagnostic performances of HFRS and other prognostic scores (THRIVE and PRE scores, SPAN-100 index) for outcome at 3-months were similar. Discussion Frailty is an independent predictor of outcome in AIS patients submitted to EST.

Background Influenza vaccine effectiveness (VE) against a spectrum of severe disease, including critical illness and death, remains poorly characterized. Methods We conducted a test-negative study in an intensive care unit (ICU) network at 10 US hospitals to evaluate VE for preventing influenza-associated severe acute respiratory infection (SARI) during the 2019–2020 season, which was characterized by circulation of drifted A/H1N1 and B-lineage viruses. Cases were adults hospitalized in the ICU and a targeted number outside the ICU (to capture a spectrum of severity) with laboratory-confirmed, influenza-associated SARI. Test-negative controls were frequency-matched based on hospital, timing of admission, and care location (ICU vs non-ICU). Estimates were adjusted for age, comorbidities, and other confounders. Results Among 638 patients, the median (interquartile) age was 57 (44–68) years; 286 (44.8%) patients were treated in the ICU and 42 (6.6%) died during hospitalization. Forty-five percent of cases and 61% of controls were vaccinated, which resulted in an overall VE of 32% (95% CI: 2–53%), including 28% (−9% to 52%) against influenza A and 52% (13–74%) against influenza B. VE was higher in adults 18–49 years old (62%; 95% CI: 27–81%) than those aged 50–64 years (20%; −48% to 57%) and ≥65 years old (−3%; 95% CI: −97% to 46%) (P = .0789 for interaction). VE was significantly higher against influenza-associated death (80%; 95% CI: 4–96%) than nonfatal influenza illness. Conclusions During a season with drifted viruses, vaccination reduced severe influenza-associated illness among adults by 32%. VE was high among young adults.

OBJECTIVES A common atrioventricular valve (CAVV) is considered to be a risk factor for early and late deaths in patients with functional single ventricle (FSV). CAVV surgery in patients with FSV is challenging and there is limited knowledge of the outcomes of CAVV repair with univentricular physiology. METHODS We reviewed all CAVV surgical procedures in patients with FSV who underwent univentricular palliation. End points of the study were survival after CAVV surgery and cumulative incidence of reoperation. RESULTS Between 1984 and 2019, 66 children with CAVV and FSV underwent single-ventricle palliation, of whom 45.5% (30/66) required CAVV surgery. Indication for surgery was moderate CAVV regurgitation in 40% (12/30) and severe CAVV regurgitation in 60% (18/30). CAVV repair was performed in 93.3% (28/30) and CAVV replacement in 6.7% (2/30). The median age and weight at surgery were 0.9 years (interquartile range 0.3–1.8) and 6.5 kg (interquartile range 3.9–8.7), respectively. Operative and late mortality were 23.3% and 8.7%, respectively. Survival and cumulative incidence of reoperation at 4 years after CAVV surgery were 68.9% [standard deviation (SD): 8.7] and 35.8% (SD: 9.1), respectively. Fontan completion was achieved in 60% (18/30). Survival at 4 years after birth was 69.7% (SD: 8.5) in 30 patients with CAVV surgery, whereas it was 83% (SD: 6.3) in 36 patients without CAVV surgery (P = 0.32). CONCLUSIONS CAVV surgery in patients with FSV is associated with substantial mortality and a high incidence of reoperation.

Aims With the implementation of saline-enhanced radiofrequency (SERF) needle-tip ablation, real-time validation of lesion formation is needed for the controllable creation of transmural lesions. The aim of the study was to analyse the ability of two-dimensional intracardiac echocardiography (2D-ICE) to guide and validate SERF ablation in real-time. Methods and results Fifty-six SERF energy deliveries at left ventricular sites of 11 dogs guided by 2D-ICE were analysed (power: 15–50 W; time: 25–120 s; irrigation saline: 60°C with 10 mL/min flow rate). Catheter tip/tissue orientation and lesion formation could be well detected by 2D-ICE in 49 (87.5%) energy deliveries. Gross pathology analysis confirmed excellent 2D-ICE lesion localization, the ability to detect transmural lesions (70% sensitivity, 47% specificity) and positive correlation between 2D-ICE and the corresponding gross pathology measurements of ‘maximal lesion depth’; (repeated measures correlation: rrm = 0.43, P = 0.012) and ‘depth at maximal lesion width’ (D@MW; rrm = 0.51, P = 0.003). The median angle between SERF catheter tip and endocardium was 76° [interquartile range (IQR) 58–83°]. The more perpendicular the catheter tip/tissue orientation was the deeper D@MW (rrm = 0.32, P = 0.045). Grade 3 microbubbles on 2D-ICE during ablation, indicating inadequate catheter tip/tissue contact, was associated with smaller lesion volumes than with Grade 1 microbubbles (284.8 mm3 [IQR 151.3–343.1] vs. 2114.1 mm3 [IQR 1437.0–3026.3], P Conclusion With excellent lesion localization and a 70% detection rate of transmural lesions, 2D-ICE is well suited to validate SERF ablation lesion formation in real-time. The catheter tip/tissue angle impacts the lesion formation and through perpendicular catheter positioning, deeper intramural areas of the myocardium can be reached.