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Background: Elevated blood pressure after endovascular thrombectomy (EVT) has been associated with an increased risk of hemorrhagic transformation and poor functional outcomes. However, the optimal hemodynamic management after EVT remains unknown, and the blood pressure course in the acute phase of ischemic stroke has not been well characterized. This study aimed to identify patient subgroups with distinct blood pressure trajectories after EVT and study their association with radiographic and functional outcomes. Methods: This multicenter retrospective cohort study included consecutive patients with anterior circulation large-vessel occlusion ischemic stroke who underwent EVT. Repeated time-stamped blood pressure data were recorded for the first 72 hours after thrombectomy. Latent variable mixture modeling was used to separate subjects into five groups with distinct postprocedural systolic blood pressure (SBP) trajectories. The primary outcome was functional status, measured on the modified Rankin Scale 90 days after stroke. Secondary outcomes included hemorrhagic transformation, symptomatic intracranial hemorrhage, and death. Results: Two thousand two hundred sixty-eight patients (mean age [±SD] 69±15, mean National Institutes of Health Stroke Scale 15±7) were included in the analysis. Five distinct SBP trajectories were observed: low (18%), moderate (37%), moderate-to-high (20%), high-to-moderate (18%), and high (6%). SBP trajectory group was independently associated with functional outcome at 90 days ( P P =0.0003 and adjusted odds ratio, 2.2 [95% CI, 1.5–3.2], P P =0.04). No significant association was found between trajectory group and hemorrhagic transformation. Conclusions: Patients with acute ischemic stroke demonstrate distinct SBP trajectories during the first 72 hours after EVT that have differing associations with functional outcome. These findings may help identify potential candidates for future blood pressure modulation trials.

Background The availability of various types of COVID-19 vaccines and diverse characteristics of the vaccines present a dilemma in vaccination choices, which may result in individuals refusing a particular COVID-19 vaccine offered, hence presenting a threat to immunisation coverage and reaching herd immunity. The study aimed to assess global COVID-19 vaccination intention, vaccine characteristics influencing vaccination acceptance and desirable vaccine characteristics influencing the choice of vaccines. Methods An anonymous cross-sectional survey was conducted between 4 January and 5 March 2021 in 17 countries worldwide. Proportions and the corresponding 95% confidence intervals (CI) of COVID-19 vaccine acceptance and vaccine characteristics influencing vaccination acceptance were generated and compared across countries and regions. Multivariable logistic regression analysis was used to determine the factors associated with COVID-19 vaccine hesitancy. Results Of the 19,714 responses received, 90.4% (95% CI 81.8–95.3) reported likely or extremely likely to receive COVID-19 vaccine. A high proportion of likely or extremely likely to receive the COVID-19 vaccine was reported in Australia (96.4%), China (95.3%) and Norway (95.3%), while a high proportion reported being unlikely or extremely unlikely to receive the vaccine in Japan (34.6%), the U.S. (29.4%) and Iran (27.9%). Males, those with a lower educational level and those of older age expressed a higher level of COVID-19 vaccine hesitancy. Less than two-thirds (59.7%; 95% CI 58.4–61.0) reported only being willing to accept a vaccine with an effectiveness of more than 90%, and 74.5% (95% CI 73.4–75.5) said they would accept a COVID-19 vaccine with minor adverse reactions. A total of 21.0% (95% CI 20.0–22.0) reported not accepting an mRNA vaccine and 51.8% (95% CI 50.3–53.1) reported that they would only accept a COVID-19 vaccine from a specific country‐of‐origin. Countries from the Southeast Asia region reported the highest proportion of not accepting mRNA technology. The highest proportion from Europe and the Americas would only accept a vaccine produced by certain countries. The foremost important vaccine characteristic influencing vaccine choice is adverse reactions (40.6%; 95% CI 39.3–41.9) of a vaccine and effectiveness threshold (35.1%; 95% CI 33.9–36.4). Conclusions The inter-regional and individual country disparities in COVID-19 vaccine hesitancy highlight the importance of designing an efficient plan for the delivery of interventions dynamically tailored to the local population. Graphic Abstract

Congenital complete heart block and acquired complete heart block are serious conduction abnormalities that may necessitate permanent pacemaker placement. Small patient size and anatomy preclude transvenous pacemaker insertion and risk subcutaneous generator pocket complications. This report describes a case of placement of a pediatric bipolar epicardial pacemaker through a right axillary incision with an intrapleural polytetrafluoroethylene membrane pocket to facilitate future generator exchange.

Background Oral squamous cell carcinoma (OSCC) is a capricious cancer with poor survival rates, even for early-stage patients. There is a pressing need to develop more precise risk assessment methods to appropriately tailor clinical treatment. Genome-wide association studies have not produced a viable biomarker. However, these studies are limited by using heterogeneous cohorts, not focusing on methylation although OSCC is a heavily epigenetically-regulated cancer, and not combining molecular data with clinicopathologic data for risk prediction. In this study we focused on early-stage (I/II) OSCC and created a risk score called the REASON score, which combines clinicopathologic characteristics with a 12-gene methylation signature, to predict the risk of 5-year mortality. Methods We combined data from an internal cohort (n = 515) and The Cancer Genome Atlas (TCGA) cohort (n = 58). We collected clinicopathologic data from both cohorts to derive the non-molecular portion of the REASON score. We then analyzed the TCGA cohort DNA methylation data to derive the molecular portion of the risk score. Results 5-year disease specific survival was 63% for the internal cohort and 86% for the TCGA cohort. The clinicopathologic features with the highest predictive ability among the two the cohorts were age, race, sex, tobacco use, alcohol use, histologic grade, stage, perineural invasion (PNI), lymphovascular invasion (LVI), and margin status. This panel of 10 non-molecular features predicted 5-year mortality risk with a concordance (c)-index = 0.67. Our molecular panel consisted of a 12-gene methylation signature (i.e., HORMAD2, MYLK, GPR133, SOX8, TRPA1, ABCA2, HGFAC, MCPH1, WDR86, CACNA1H, RNF216, CCNJL), which had the most significant differential methylation between patients who survived vs. died by 5 years. All 12 genes have already been linked to survival in other cancers. Of the genes, only SOX8 was previously associated with OSCC; our study was the first to link the remaining 11 genes to OSCC survival. The combined molecular and non-molecular panel formed the REASON score, which predicted risk of death with a c-index = 0.915. Conclusions The REASON score is a promising biomarker to predict risk of mortality in early-stage OSCC patients. Validation of the REASON score in a larger independent cohort is warranted.

Purpose We compared work outcomes in patients with oropharyngeal cancer (OPC), randomized to intensity-modulated proton (IMPT) versus intensity-modulated photon therapy (IMRT) for chemoradiation therapy (CRT). Patients and Methods In 147 patients with stage II-IVB squamous cell OPC participating in patient-reported outcomes assessments, a prespecified secondary aim of a randomized phase II/III trial of IMPT (n = 69) versus IMRT (n = 78), we compared absenteeism, presenteeism (i.e., the extent to which an employee is not fully functional at work), and work productivity losses. We used the work productivity and activity impairment questionnaire at baseline (pre-CRT), at the end of CRT, and at 6 months, 1 year, and 2 years. A one-sided Cochran-Armitage test was used to analyze within-arm temporal trends, and a χ2 test was used to compare between-arm differences. Among working patients, at each follow-up point, a 1-sided Wilcoxon rank-sum test was used to compare work-productivity scores. Results Patient characteristics in IMPT versus IMRT arms were similar. In the IMPT arm, within-arm analysis demonstrated that an increasing proportion of patients resumed working after IMPT, from 60% (40 of 67) pre-CRT and 71% (30 of 42) at 1 year to 78% (18 of 23) at 2 years (P = 0.025). In the IMRT arm, the proportion remained stable, with 57% (43 of 76) pre-CRT, 54% (21 of 39) at 1 year, and 52% (13 of 25) working at 2 years (P = 0.47). By 2 years after CRT, the between-arm difference between patients who had IMPT and those who had IMRT trended toward significance (P = 0.06). Regardless of treatment arm, among working patients, the most severe work impairments occurred from treatment initiation to the end of CRT, with significant recovery from absenteeism, presenteeism, and productivity impairments by the 2-year follow-up (P Conclusion In patients with OPC receiving curative CRT, patients randomized to IMPT demonstrated increasing work and productivity recovery trends. Studies are needed to identify mechanisms underlying head and neck CRT treatment causing work disability and impairment.

Previous studies indicate that oxytocin (OT) administration reduces body weight in high-fat diet (HFD)-induced obese (DIO) rodents through both reductions in food intake and increases in energy expenditure. We recently demonstrated that chronic hindbrain [fourth ventricular (4V)] infusions of OT evoke weight loss in DIO rats. Based on these findings, we hypothesized that chronic 4V OT would elicit weight loss in DIO mice. We assessed the effects of 4V infusions of OT (16 nmol/day) or vehicle over 28 days on body weight, food intake, and body composition. OT reduced body weight by approximately 4.5% ± 1.4% in DIO mice relative to OT pretreatment body weight ( P < 0.05). These effects were associated with reduced adiposity and adipocyte size [inguinal white adipose tissue (IWAT)] ( P < 0.05) and attributed, in part, to reduced energy intake ( P < 0.05) at a dose that did not increase kaolin intake ( P = NS). OT tended to increase uncoupling protein-1 expression in IWAT (0.05 < P < 0.1) suggesting that OT stimulates browning of WAT. To assess OT-elicited changes in brown adipose tissue (BAT) thermogenesis, we examined the effects of 4V OT on interscapular BAT temperature ( TIBAT). 4V OT (1 µg) elevated TIBAT at 0.75 ( P = 0.08), 1, and 1.25 h ( P < 0.05) postinjection; a higher dose (5 µg) elevated TIBAT at 0.75-, 1-, 1.25-, 1.5-, 1.75- ( P < 0.05), and 2-h (0.05 < P < 0.1) postinjection. Together, these findings support the hypothesis that chronic hindbrain OT treatment evokes sustained weight loss in DIO mice by reducing energy intake and increasing BAT thermogenesis at a dose that is not associated with evidence of visceral illness.

Our report describes a female presenting with vomiting, fever, coma and right hemiplegia at 26 months of age. Biochemical tests revealed hyperammonemia, hyperlactatemia, elevated glutamine level, elevated transaminase and disorder of prothrombin time. She was priory diagnosed with urea cycle disorders (UCDs). UCDs are caused by mutations in eight genes that regulate the synthesis of enzymes and cofactors involved in urea metabolism. Singleton whole exome sequencing was applied to screen causative variants in these genes in the patient at 6 years of age. The result showed one heterozygous stop loss mutation c.1065A>G in the OTC gene as a potential disease causing in the patient. The mutation c.1065A>G leads to alternation of stop codon to tryptophan, resulting in elongation of fourteen amino acids in ornithine transcarbamylase (OTC) protein (p.Ter355TrpextTer14). Sanger sequencing in the family revealed the mutation c.1065A>G was not present in healthy parents and brother. Therefore, this mutation is considered as a de novo mutation in the patient. The mutation c.1065A>G was conferred to pathogenic according to the standards and guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology with 1 strong (PS2), 3 moderate (PM2, PM4 and PM5) and 1 support criteria (PP2). Although OTC deficiency is an X-linked recessive inheritance, approximately 15% of females carrying heterozygous variants showed the late onset OTC deficiency. Therefore, in combination of clinical presentations, laboratory findings and molecular genetic analyses, we made a definitive diagnosis of the patient with late onset OTC deficiency, a disorder of UCDs.

IntroductionBCG vaccination modulates immune responses to unrelated pathogens. This off-target effect could reduce the impact of emerging pathogens. As a readily available, inexpensive intervention that has a well-established safety profile, BCG is a good candidate for protecting healthcare workers (HCWs) and other vulnerable groups against COVID-19.Methods and analysisThis international multicentre phase III randomised controlled trial aims to determine if BCG vaccination reduces the incidence of symptomatic and severe COVID-19 at 6 months (co-primary outcomes) compared with no BCG vaccination. We plan to randomise 10 078 HCWs from Australia, The Netherlands, Spain, the UK and Brazil in a 1:1 ratio to BCG vaccination or no BCG (control group). The participants will be followed for 1 year with questionnaires and collection of blood samples. For any episode of illness, clinical details will be collected daily, and the participant will be tested for SARS-CoV-2 infection. The secondary objectives are to determine if BCG vaccination reduces the rate, incidence, and severity of any febrile or respiratory illness (including SARS-CoV-2), as well as work absenteeism. The safety of BCG vaccination in HCWs will also be evaluated. Immunological analyses will assess changes in the immune system following vaccination, and identify factors associated with susceptibility to or protection against SARS-CoV-2 and other infections.Ethics and disseminationEthical and governance approval will be obtained from participating sites. Results will be published in peer-reviewed open-access journals. The final cleaned and locked database will be deposited in a data sharing repository archiving system.Trial registrationClinicalTrials.gov NCT04327206

The coexistence of multiple myeloma and chronic myelomonocytic leukemia in the same patient is a rare entity. Here we describe a case of an 80-year-old man who presented to our hospital with symptoms of dyspnea and found to have anemia and leukocytosis with peripheral monocytosis. Bone marrow biopsy, flow cytometry, and fluorescence in situ hybridization studies were consistent with a laboratory diagnosis of multiple myeloma and chronic myelomonocytic leukemia. Due to advanced age and multiple comorbidities, the patient was treated conservatively. At 26 months follow-up, the patient continues to do well.

Background and Purpose: High blood pressure (BP) variability after endovascular stroke therapy is associated with poor outcome. Conventional BP variability measures require long recordings, limiting their utility as a risk assessment tool to guide clinical decision-making. Here, we performed rapid assessment of BP variability by spectral analysis and evaluated its association with early clinical improvement and long-term functional outcomes. Methods: We conducted a prospective study of 146 patients with anterior circulation ischemic stroke who underwent successful endovascular stroke therapy. Spectral analysis of 5-minute recordings of beat-to-beat BP was used to quantify BP variability. Outcomes included initial clinical response and modified Rankin Scale at 90 days. Results: Increased BP variability at high frequencies was independently associated with poor functional outcome at 90 days (adjusted odds ratio [aOR], 1.85 [95% CI, 1.07–3.25], P =0.03; low-/high-frequency ratio aOR, 0.67 [95% CI, 0.46–0.92], P =0.02) and reduced likelihood of an early neurological recovery (aOR, 0.62 [95% CI, 0.44–0.91], P =0.01 and aOR, 1.37 [95% CI, 1.03–1.87], P =0.04, respectively). Conclusions: High-frequency BP oscillations after successful reperfusion may be harmful and associate with a decreased likelihood of neurological recovery and favorable functional outcomes. Rapid assessment of BP variability throughout the postreperfusion period is feasible and may allow for a more personalized BP management.

Background Oral squamous cell carcinoma (OSCC) has poor survival rates. There is a pressing need to develop more precise risk assessment methods to tailor clinical treatment. Epigenome-wide association studies in OSCC have not produced a viable biomarker. These studies have relied on methylation array platforms, which are limited in their ability to profile the methylome. In this study, we use MethylCap-Seq (MC-Seq), a comprehensive methylation quantification technique, and brush swab samples, to develop a noninvasive, readily translatable approach to profile the methylome in OSCC patients. Methods Three OSCC patients underwent collection of cancer and contralateral normal tissue and brush swab biopsies, totaling 4 samples for each patient. Epigenome-wide DNA methylation quantification was performed using the SureSelectXT Methyl-Seq platform. DNA quality and methylation site resolution were compared between brush swab and tissue samples. Correlation and methylation value difference were determined for brush swabs vs. tissues for each respective patient and site (i.e., cancer or normal). Correlations were calculated between cancer and normal tissues and brush swab samples for each patient to determine the robustness of DNA methylation marks using brush swabs in clinical biomarker studies. Results There were no significant differences in DNA yield between tissue and brush swab samples. Mapping efficiency exceeded 90% across all samples, with no differences between tissue and brush swabs. The average number of CpG sites with at least 10x depth of coverage was 2,716,674 for brush swabs and 2,903,261 for tissues. Matched tissue and brush swabs had excellent correlation (r = 0.913 for cancer samples and r = 0.951 for normal samples). The methylation profile of the top 1,000 CpGs was significantly different between cancer and normal samples (mean p-value = 0.00021) but not different between tissues and brush swabs (mean p-value = 0.11). Conclusions Our results demonstrate that MC-Seq is an efficient platform for epigenome profiling in cancer biomarker studies, with broader methylome coverage than array-based platforms. Brush swab biopsy provides adequate DNA yield for MC-Seq, and taken together, our findings set the stage for development of a non-invasive methylome quantification technique for oral cancer with high translational potential.

Background: Heart failure is a common clinical syndrome and is the final stage of most cardiovascular diseases. Nowadays, the role of left atrium in cardiovascular diseases, especially in HF diseases, is more and more important. At the early stage of heart failure, the size and pump function of left atrium are increased. When the left ventricular function is reduced significantly, left atrial function is alo impaired. Aims of the study: assess size and function of left atrium in patient with heart failure reduced ejection fraction (HFrEF). Establishing the association between two indexs above with some clinical and subclinical characteristics. Subjects and method: 51 HFrEF patients in Hospital of Hue University of Medicine and Pharmacy, who have including criteria. Cross-sectional study. Results: LAVI (ml/m2): 43.19 ± 12.48 ml/m2, percentage of large left atrial patents is 80.4%. LATEF (%): 31.93 ± 7.72%. LAVI has correlation with: LVEDV (r= 0,45); LVESV (r= 0,43); NT-proBNP (r= 0.371). There is a difference LAVI of diastolic dysfunction grades (r= 0.011), There is a difference LAVI of NYHA class (r= 0.016). LATEF has correlation with NTproBNP (r= -0.349). Conclusion: The left atrium’s size is increased and its function is reduced in HFrEF patient. There is a positive correlation between LAVI and LVEDV, LVESV, NTproBNP. The LAVI varies with the diastolic dysfunction grade. And there is a negative correlation between LATEF and NTproBNP. Key words: heart failure reduced ejection fraction; size of left atrium, function of left atrium

Ultrasonic or bipolar radiofrequency energy devices are routinely used for dissection and hemostasis during thyroidectomy. We report a single-center, prospective, randomized controlled trial comparing the utility and outcomes of Harmonic Focus, an ultrasonic coagulating shear device (UCSD), versus Ligasure Small Jaw, an electrothermal bipolar vessel sealer (EBVS) in thyroidectomy (NCT01765686). Between December 2012 to January 2016, eligible patients were randomized to undergo hemithyroidectomy using either a UCSD or an EBVS. The primary outcome was duration of surgery. Secondary outcomes included blood loss, postoperative complications, ease of device use, ease of device set-up, vocal cord function, postoperative wound drainage, pain score, and adverse events. Of 110 patients assessed for eligibility, 100 were randomly allocated (UCSD: 49 patients; EBVS: 51 patients) and analyzed by intention-to-treat. There were no differences in specimen delivery time, total duration of surgery, wound drainage, and adverse events between the two groups. The UCSD group had a greater proportion of patients with higher postoperative pain scores in the first 72 h (8.1% vs. 2.0%, p = 0.043). Surgeons reported greater ease of use for the UCSD (49% vs. 27%; p = 0.005), while operating room staff favored the EBVS (60% vs. 33%, p = 0.005). Energy devices are equally effective in reducing thyroidectomy operative times, with no differences in the duration of surgery, drainage, or adverse events. Use of the UCSD was associated with higher postoperative pain scores, but was favored by the surgeons, likely due to the ability to perform fine dissection with the device itself.

Objectives This study was conducted to compare clinical outcomes of fidaxomicin versus oral vancomycin in the management of severe Clostridium difficile infection (CDI). Methods The investigation was a retrospective, multicentre, propensity score-matched analysis using a national clinical administrative database. Veterans treated for severe CDI from any Veterans Affairs Medical Center between 1 June 2011 and 30 June 2017 were included if they received fidaxomicin or an oral vancomycin regimen for treatment. The two groups were matched by the nearest-neighbour method from a propensity score derived from independent variables associated with the selection of a fidaxomicin course. Results Propensity score matching resulted in two well-matched cohorts consisting of 213 fidaxomicin and 639 oral vancomycin courses. No statistically-significant difference was found for the primary outcome of combined clinical failure or recurrence (68/213 (31.9%) versus 163/639 (25.5%), respectively, p 0.071). Additionally, no statistically significant differences were found for the secondary outcomes of 30-day (23/213 (10.8%) versus 75/639 (11.7%), respectively, p 0.71), 90-day (48/213 (22.5%) versus 140/639 (21.9%), respectively, p 0.85), and 180-day mortality (62/213 (29.1%) versus 186/639 (29.1%), respectively, p 1.0) between the two treatment groups. Conclusions Courses of fidaxomicin or oral vancomycin for severe CDI resulted in similar treatment outcomes. Study findings are consistent with current treatment guideline recommendations for the use of either agent in the management of severe CDI.

Inappropriate use of antibiotics in animal production system is one of the major factors leading to the antibiotic resistance (ABR) development. In Vietnam, the ABR situation is crucial as antibiotics have been used indiscriminately for disease prevention and as growth promoters in animals. Thus, a thorough understanding on the ABR in veterinary settings would be beneficial to the Vietnam public health authority in formulating timely interventions. This review aimed to provide information on the current status of antibiotic usage in animal husbandry in Vietnam, identified gaps in research, and suggested possible solutions to tackle ABR. To this end, data on ABR in animals were extracted from 3 major electronic databases (PubMed, Web of Science, and ScienceDirect) in the period of January 2013-December 2020. The review findings were reported according to PRISMA, which highlighted the emergence and persistence of ABR in bacterial isolates, including Escherichia coli, Enterococcus spp., and Salmonella species, obtained from pigs and poultry. The lack of awareness of Vietnamese farmers on the antibiotic utilization guidelines was one of the main causes driving the animal ABR. Hence, this paper calls for interventions to restrict antibiotics use in food-producing animals by national action plan and antibiotics control programs. Additionally, studies to evaluate knowledge, attitude, and practice (KAP) of the community are required to promote rational use of antibiotics in all sectors.

Purpose: Endovascular thrombectomy (ET) is the standard of care in large vessel occlusion (LVO) stroke, with CTA and CT/MR perfusion guiding patient selection. We hypothesized that radiomics imaging features extracted from admission CTAs could predict post-ET outcome. Methods: We included patients with anterior circulation LVO who had ET at our institute, 01/2013–12/2019. We extracted 1116 radiomics features from each MCA supply territory. We applied and evaluated a framework of 6 feature selection techniques and 6 machine-learning classifiers for prediction of discharge and 3-month follow-up outcome, defined as favorable (modified Rankin score, mRS≤2) vs poor (mRS>2). Post-ET reperfusion success was determined by the modified thrombolysis in cerebral infarction (mTICI) scale. We used Bayesian optimization for hyperparameter tuning and performed 20 repetitions of 5-fold cross-validation, for which the average area under the receiver operating characteristic curve (AUC) across validation folds for each of our 36 feature-selection/machine-learning combinations was calculated. Results: 501 patients (228 male) were included, with mean age 70.3±15.5 years, median NIH stroke score 15 (interquartile range=6–24), and occlusions in ICA (n=123), M1 (n=318), and/or M2 (n=154). Functional outcome was available for 496 patients at discharge and for 375 at 3-months. Best performing models combining NIHSS, age, gender, IV thrombolytic treatment, and post-ET mTICI achieved an average AUC of 0.82±0.05, while models trained on radiomics and mTICI achieved an AUC of 0.71±0.05. Conclusion: The combination of automatically extracted CTA radiomics features and post-ET reperfusion success (mTICI) can predict LVO stroke functional outcome – even without baseline clinical variables. Such models may guide treatment decisions by predicting outcome for various degrees of post-ET reperfusion and automating assessment of baseline stroke CTA scans.

Introduction: Infarct growth is affected by the collateral blood supply and ischemic tolerance and thus unlikely linear. This study aimed to better characterize infarct growth rates (IGR) after large-vessel occlusion (LVO) stroke. Methods: We retrospectively identified patients with anterior LVO stroke who underwent mechanical thrombectomy (MT) at two comprehensive stroke centers. Core infarct volumes at presentation (CBF Results: Of the 361 patients (age 68 ± 15, 55% female, NIHSS 14 ± 6) included in the analysis, 282 (78.1%) had successful reperfusion, and 150 (41.6%) achieved a good outcome (mRS ≤2). IGR showed an exponential growth pattern (Figure 1). There was no significant difference in the median IGR 1 between the poor and good outcome groups (2.3 vs. 1 ml, p=0.061). The median IGR 2 in patients with poor outcome was significantly higher when compared to those in the good outcome group (IGR 14.1ml/h vs. 4.62ml/h, p Conclusions: We identified an exponential infarct growth pattern after LVO stroke that differs in relation to outcome. High IGR in the interval from CTP to reperfusion is associated with worse outcomes, emphasizing the importance of future research into therapeutic approaches to slow down infarct progression.

Introduction: Decreases in blood pressure (BP) during endovascular therapy (EVT) have been associated with infarct progression and worse outcome after large vessel occlusion (LVO) stroke. However, BP trajectories in the hyperacute phase prior to EVT have not been well characterized. We used high-frequency BP and hemodynamic monitoring to study the timing of BP reductions during the hyperacute period of stroke and evaluated their relation to infarct progression and functional outcome. Methods: We prospectively enrolled patients with anterior circulation LVO stroke undergoing EVT. BP and cardiac hemodynamic variables were recorded every 20 seconds from ER admission until the end of EVT using non-invasive finger plethysmography. Patients underwent initial CT perfusion imaging and a follow-up MRI at 24 hours to calculate infarct growth. The following hemodynamic parameters were defined as exposure variables: the difference between admission MAP and lowest MAP (ΔMAP), MAP drop> 20% from admission, MAP Results: 45 patients underwent continuous BP monitoring (age 72±17; 58% female; NIHSS 13±6). Aggregated time series data revealed a marked BP reduction around the time of imaging from which patients recovered (mean SBP 33 mmHg, duration 18 min). A sustained decrease in BP was observed after groin puncture without return to baseline BP levels. A linear regression analysis revealed a 13ml infarct growth for every 10 mmHg reduction in ΔMAP (p=0.054). Patients were divided into two groups based on median ΔMAP = 29. Those with ΔMAP ≤29 had better functional outcome at 90 days (34.78% vs. 9.09%, p = 0.038). Conclusion: Marked and frequently iatrogenic BP reductions occur around the time of initial imaging and may present a potential target for therapeutic intervention. Decrease in blood pressure before reperfusion may increase the risk of infarct progression and poor functional outcome. Changes in cardiac hemodynamic variables throughout the acute stroke period suggest a potential role for fluid resuscitation for hemodynamic optimization.

Introduction: Despite treatment with mechanical thrombectomy (MT), some patients fail to regain functional independence at 90 days. The growth of the ischemic core varies across patients, and likely reflects differences in collateral flow and ischemic tolerance. In this study, we sought establish the optimal infarct growth rate (IGR) threshold to differentiate between slow and fast progressors and assess its ability to predict poor outcome. Methods: We retrospectively identified patients with anterior large-vessel occlusion (LVO) stroke with successful MT (mTICI ≥ 2b) at two comprehensive stroke centers. Final infarct volume (FIV) was calculated from post-MT Diffusion-weighted MRI. Assuming relative stability of the FIV after successful reperfusion, we defined IGR as [FIV (ml)] / [Time from stroke onset to reperfusion (hours)]. Good clinical outcome was defined as a modified Rankin scale score (mRS) ≤2. We used Receiver Operating Characteristics (ROC) analysis to calculate the optimal IGR threshold with high specificity for predicting a poor outcome. Multivariate logistic regression analysis was performed to evaluate the association of fast progressors (IGR ≥ 7.14 ml/h) on the poor functional outcome and mortality. Results: Of the 212 patients (age 68 ± 15, 51% female, NIHSS 15 ± 7) included, 110 (51.8%) patients had a poor outcome. The median IGR was significantly higher in patients with poor compared to good outcome (7 ml/h vs. 3.1 ml/h, p Conclusions: IGR is an independent predictor of poor outcome and mortality in patients with successful MT. Early identification of this population might help to institute therapeutic strategies of accelerating reperfusion and slowing the IGR.

Introduction: Decreases in blood pressure (BP) during thrombectomy are associated with infarct progression and worse outcomes. Many patients present first to a primary stroke center (PSC) and are later transferred to a comprehensive stroke center (CSC) to undergo thrombectomy. During this period, important BP variations might occur. We evaluated the association of BP reductions with neurological worsening and functional outcomes. Methods: We prospectively collected hemodynamic, clinical, and radiographic data on consecutive patients with LVO ischemic stroke who were transferred from a PSC for possible thrombectomy between 2018 and 2020. We assessed systolic BP (SBP) and mean arterial pressure (MAP) at five time points: earliest recorded, average pre-PSC, PSC admission, average PSC, and CSC admission. We measured neurologic worsening as a change in NIHSS (ΔNIHSS) from PSC to CSC >3 and functional outcome using the modified Rankin Scale (mRS) at discharge and 90 days. Relationships between variables of interest were evaluated using linear regression. Results: Of 91 patients (mean age 70±16 years, mean NIHSS 12) included, 13 (14%) experienced early neurologic deterioration (ΔNIHSS>3), and 34 (37%) achieved a good outcome at discharge (mRS Conclusions: Patients with poor outcomes have higher BP throughout the pre-CSC period, possibly reflecting an augmented hypertensive response. Reductions in SBP and MAP before arrival at the CSC are associated with neurologic worsening. These results suggest that BP management strategies in the pre-CSC period to avoid large reductions in BP may improve outcomes in patients affected by LVO stroke.

Background: Nanocovax is a recombinant severe acute respiratory syndrome coronavirus 2 subunit vaccine composed of full-length prefusion stabilized recombinant SARS-CoV-2 spike glycoproteins (S-2P) and aluminum hydroxide adjuvant. Methods: We conducted a dose-escalation, open label trial (phase 1) and a randomized, double-blind, placebo-controlled trial (phase 2) to evaluate the safety and immunogenicity of the Nanocovax vaccine (in 25 microgram (mcg), 50 mcg, and 75 mcg doses, aluminum hydroxide adjuvanted). In phase 1, 60 participants received two intramuscular injection of the vaccine following dose-escalation procedure. The primary outcomes were reactogenicity and laboratory tests to evaluate the vaccine safety. In phase 2 which involved in 560 healthy adults, the primary outcomes are vaccine safety, and anti-S IgG antibody response. Secondary outcomes were surrogate virus neutralization, wild-type SARS-CoV-2 neutralization, and T-cell responses by intracellular staining (ICS) for interferon gamma (IFNg). Anti-S IgG and neutralizing antibody levels were compared with convalescent serum samples from symptomatic Covid-19 patients. Findings: For phase 1 study, no serious adverse events (SAE) were observed for all 60 participants. Most adverse events (AE) were grade 1 and disappeared shortly after injection. For phase 2 study, after randomization, 480 participants were assigned to receive the vaccine with adjuvant, and 80 participants were assigned to receive placebo. Reactogenicity was absent or mild in the majority of participants and of short duration (mean ≤3 days). Unsolicited adverse events were mild in most participants. There were no serious adverse events related to Nanocovax. Regarding the immunogenicity, Nanocovax induced robust anti-S antibody responses. In general, there humoral responses were similar among vaccine groups up to day 90. Anti S-IgG levels and neutralizing antibody titers at the peak response on day 42 were all higher than those of convalescent sera. Interpretation: Up to day 90, Nanocovax was found to be safe, well tolerated, and induced robust immune responses. 25 mcg was selected for a phase 3 trial to evaluate the vaccine efficacy. Trial Registration: ClinicalTrials.gov number, NCT04683484. NCT04683484, registration date in clinicaltrial.gov is Dec24, 2020, We has started our Phase 1 clinical trial in Vietnam on Dec 17, 2020, Funding: Research funded by Nanogen Pharmaceutical Biotechnology JSC., and the Ministry of Science and Technology of Vietnam Declaration of Interest: The following authors Thuy Phuong Nguyen, Hiep Khong, Tri Minh Le, Tuyen Thi Ngoc Trang, Thanh Thi Dinh, Thuong Van Vo, Thao Thi Thu Vu, Quynh Bao Phuong Nguyen, Vuong Tan Phan, Vinh The Tran, Mai Thi Nhu Tran, Truc Thi Thanh Nguyen, Phat Tan Ha, Hieu Trong Huynh, Khanh Duy Nguyen, Chung Chinh Doan, Thuan Trong Ung, Si Minh Do are employees of Nanogen Pharmaceutical Biotechnology JSC. All other authors declare no competing interests. Ethical Approval: The trials were designed and funded by Nanogen Pharmaceutical Biotechnology JSC and the Ministry of Science and Technology (MOST) of Vietnam. The trial protocol was approved by the Ethics Committee/Protocol Review Board of the Ministry of Health (Vietnam)

This paper proposes recommendations for probiotics in pediatric gastrointestinal diseases in the Asia-Pacific region. Evidence-based recommendations and randomized controlled trials in the region are included. Cultural aspects, health management issues and economic factors were also considered. Final recommendations were approved by utilizing a modified Delphi process and applying the Likert scale in an electronic voting process. Bacillus clausii was recommended as an adjunct treatment with oral rehydration solution for acute viral diarrhea. B. clausii may also be considered for prevention of antibiotic-associated diarrhea, Clostridium difficile-induced diarrhea, and as adjunct treatment of Helicobacter pylori. There is insufficient evidence for recommendations in other conditions. Despite a diversity of epidemiological, socioeconomical and health system conditions, similar recommendations currently apply to most Asia-Pacific countries. Ideally, these need to be validated with local randomized-controlled trials.

Background and Purpose: We aim to examine effects of collateral status and post-thrombectomy reperfusion on final infarct distribution and early functional outcome in patients with anterior circulation large vessel occlusion ischemic stroke. Methods: Patients with large vessel occlusion who underwent endovascular intervention were included in this study. All patients had baseline computed tomography angiography and follow-up magnetic resonance imaging. Collateral status was graded according to the criteria proposed by Miteff et al and reperfusion was assessed using the modified Thrombolysis in Cerebral Infarction (mTICI) system. We applied a multivariate voxel-wise general linear model to correlate the distribution of final infarction with collateral status and degree of reperfusion. Early favorable outcome was defined as a discharge modified Rankin Scale score ≤2. Results: Of the 283 patients included, 129 (46%) had good, 97 (34%) had moderate, and 57 (20%) had poor collateral status. Successful reperfusion (mTICI 2b/3) was achieved in 206 (73%) patients. Poor collateral status was associated with infarction of middle cerebral artery border zones, whereas worse reperfusion (mTICI scores 0–2a) was associated with infarction of middle cerebral artery territory deep white matter tracts and the posterior limb of the internal capsule. In multivariate regression models, both mTICI ( P P P P =0.058), predicted favorable outcome at discharge. Conclusions: In this cohort of patients with large vessel occlusion stroke, both the collateral status and endovascular reperfusion were strongly associated with middle cerebral artery territory final infarct volumes. Our findings suggesting that baseline collateral status predominantly affected middle cerebral artery border zones infarction, whereas higher mTICI preserved deep white matter and internal capsule from infarction; may explain why reperfusion success—but not collateral status—was among the independent predictors of favorable outcome at discharge. Infarction of the lentiform nuclei was observed regardless of collateral status or reperfusion success.

OBJECTIVE While the benefit of mechanical thrombectomy (MT) for patients with anterior circulation acute ischemic stroke with large-vessel occlusion (AIS-LVO) has been clearly established, difficult vascular access may make the intervention impossible or unduly prolonged. In this study, the authors evaluated safety as well as radiographic and functional outcomes in stroke patients treated with MT via direct carotid puncture (DCP) for prohibitive vascular access. METHODS The authors retrospectively studied patients from their prospective AIS-LVO database who underwent attempted MT between 2015 and 2018. Patients with prohibitive vascular access were divided into two groups: 1) aborted MT (abMT) after failed transfemoral access and 2) attempted MT via DCP. Functional outcome was assessed using the modified Rankin Scale at 3 months. Associations with outcome were analyzed using ordinal logistic regression. RESULTS Of 352 consecutive patients with anterior circulation AIS-LVO who underwent attempted MT, 37 patients (10.5%) were deemed to have prohibitive vascular access (mean age [± SD] 82 ± 11 years, mean National Institutes of Health Stroke Scale [NIHSS] score 17 ± 5, with females accounting for 75% of the patients). There were 20 patients in the DCP group and 17 in the abMT group. The two groups were well matched for the known predictors of clinical outcome: age, sex, and admission NIHSS score. Direct carotid access was successfully obtained in 19 of 20 patients. Successful reperfusion (thrombolysis in cerebral infarction score 2b or 3) was achieved in 16 (84%) of 19 patients in the DCP group. Carotid access complications included an inability to catheterize the carotid artery in 1 patient, neck hematomas in 4 patients, non–flow-limiting common carotid artery (CCA) dissections in 2 patients, and a delayed, fatal carotid blowout in 1 patient. The neck hematomas and non–flow-limiting CCA dissections did not require any subsequent interventions and remained clinically silent. Compared with the abMT group, patients in the DCP group had smaller infarct volumes (11 vs 48 ml, p = 0.04), a greater reduction in NIHSS score (−4 vs +2.9, p = 0.03), and better functional outcome (shift analysis for 3-month modified Rankin Scale score: adjusted OR 5.2, 95% CI 1.02–24.5; p = 0.048). CONCLUSIONS DCP for emergency MT in patients with anterior circulation AIS-LVO and prohibitive vascular access is safe and effective and is associated with higher recanalization rates, smaller infarct volumes, and improved functional outcome compared with patients with abMT after failed transfemoral access. DCP should be considered in this patient population.

Background: Ornithine transcarbamylase deficiency (OTCD) is an X- linked recessive disorder and the most common error of the urea cycle, caused by the mutations in the OTC gene. Due to X-inactivation, 15–20% of female carriers present symptoms of OTCD at late onset. Early diagnosis of OTCD by molecular analysis in females is highly desirable. The aim of the study was to identify the mutations in two unrelated Vietnamese girls suspected with OTCD and the carriers in their families for definitive diagnosis and proper counseling.Case Presentation: Two patients presented with an acute encephalopathy at the first admission. Biochemical tests revealed hyperammonemia, hyperlactatemia, elevated glutamine level, elevated transaminase, elevated urinary orotic and uracil acid levels, and disorder of prothrombin time. Brain magnetic resonance imaging indicated cerebral edema. Based on the clinical and laboratory results, the two patients were diagnosed with urea cycle disorders. Therefore, the two patients were managed by stopping feeding, with infused glucose, l-carnitine, l-arginine, and sodium benzoate, and with hemofiltration. The two patients were alert and recovered with normal blood ammonia levels after 72 h of treatment. The family history of patient 1 showed that her brother died at 4 days of age due to a coma and dyspnea, while her parents were asymptomatic. Variable phenotypes were observed in three generations of the patient 2's family, including asymptomatic (mother), affected female adults dying at the first symptom (grandmother and aunt), and affected males dying in the first week of life (uncle, cousin, and siblings). Whole-exome sequencing showed two mutations in the OTC gene, including one novel missense mutation, c.365A>T, in the patient 1 and one previously reported splicing mutation, c.717+1G>A, in the patient 2. The two mutations are evaluated as likely pathogenic and pathogenic, respectively, according to the recommendations of the American College of Medical Genetics and Genomics (ACMG). Genetic analyses in the families indicated the mothers were heterozygous.Conclusion: Clinical, biochemical, and molecular findings accurately diagnosed the two patients with late-onset OTCD. Our results explained the genetic causes and proposed the risk in the patients' families, which could be useful for genetic counseling and monitoring in prenatal diagnosis.

Introduction: Blood pressure (BP) is an important modifiable parameter after endovascular thrombectomy (EVT). Observational studies have found associations between elevated BP after EVT with hemorrhagic transformation and poor functional outcome. However, blood pressure course after EVT has not been well characterized and optimal hemodynamic management in the immediate post-stroke period remains unresolved. We utilized blood pressure data up to 72 hours after EVT to identify distinct systolic BP (SBP) trajectories and studied their associations with functional outcome. Methods: We retrospectively studied a multicenter cohort of 1060 patients with large-vessel occlusion stroke who underwent EVT. BP was recorded non-invasively recorded at least hourly for the first 72 hours. Functional outcome was assessed using the modified Rankin scale (mRS). Favorable functional outcome was defined as mRS &lt. Latent variable mixture modeling was applied to identify patient subgroups that have comparable SBP trajectories. All analyses were adjusted for age, admission NIHSS, and recanalization status. Results: One thousand sixty patients (mean age 70±15, mean NIHSS 16) were included in the analysis. Five distinct SBP trajectories were identified: (1) low (17%), (2) moderate (38%), (3) moderate-to-high (21%), (4) high-to-moderate (17%), and (5) high (7%) (Figure 1A). SBP trajectory group was an independent predictor of functional outcome at discharge (p=0.001) and 90 days (p=0.010, Figure 1B). Patients with high and high-to-moderate SBP trajectories had a significantly higher odds of an unfavorable outcome at 90 days (adjusted OR 2.3, 95%CI 1.2 - 4.3, p=0.01 and adjusted OR 4, 95% CI 1.5-10.7, p=0.06, respectively) Conclusions: During the first 72 hours after EVT, acute ischemic stroke patients show distinct SBP trajectories, which differ in relation to functional outcome. The findings may help recognize potential candidates for future blood pressure control trials.

Introduction: Recent trials have demonstrated the benefit of endovascular therapy (EVT) beyond 6 hours of symptom onset. However, the importance of time to reperfusion (TTR) in the extended time window has recently been questioned. Given the variability of infarct growth rate (IGR), the time delay until reperfusion may have greater consequences for those with rapidly progressing infarcts, and identifying such patients is essential for improving outcomes. We tested the hypothesis that TTR is more closely associated with functional outcome in patients with rapidly progressing infarcts compared to their slow-progressing counterparts. Methods: We retrospectively identified 106 patients at our center’s prospectively collected stroke database with anterior circulation large-vessel occlusion stroke and known time of symptom onset. Patients underwent initial CT perfusion imaging (CTP), EVT and and follow-up MRI at 24 hours. Core infarct volumes at presentation (CBF Results: 35 fast progressors (age 71±14, 17 F, TTR 288±91 minutes, mean IGR 21±24 mL/hour) and 71 slow progressors (age 71±17, 48 F, TTR 374±211 minutes, mean IGR 1.0±1.5 mL/hour) were identified. Fast progressors had higher admission NIHSS scores (18±6 vs 13±7, p Conclusions: In patients with rapidly progressing infarcts (≥5 mL/hour), TTR was associated with worse functional outcomes at 90 days compared to slow progressors. Identifying such patients may be critical for appropriate triage and rapid delivery of acute stroke care.

Introduction: Identification of patients likely to develop midline shift (MLS) after large-vessel occlusion (LVO) stroke is essential for appropriate triage and patient disposition. Studies have identified clinical and radiographic predictors of MLS, but with limited accuracy. Using an innovative assessment of cerebral autoregulation, we sought to develop an accurate predictive model for MLS. Methods: We prospectively enrolled 73 patients with LVO stroke. Beat-by-beat cerebral blood flow (transcranial Doppler) and arterial pressure (arterial catheter or finger photoplethysmography) were recorded within 24 hours of the stroke, and a 24-hour brain MRI was obtained to determine infarct volume and MLS. Autoregulatory function was quantified from pressure-flow relation via projection pursuit regression (PPR), allowing for characterization of 5 hemodynamic markers (Figure 1A). We assessed the predictive relation of autoregulatory capacity and radiological and clinical variables to MLS using recursive classification tree models. Results: PPR successfully quantified autoregulatory function in 50/73 (68.5%) patients within 24 hours of LVO ischemic stroke (age 63.9±13.6, 66% F, NIHSS 15.8±6.7). Of these 50 patients, most (78%) underwent endovascular therapy. Thirteen (26%) experienced 24-h MLS; in these patients, infarct volumes were larger (140.2 vs. 48.6 mL, P ), and ipsilateral (but not contralateral) falling slopes were steeper (1.1 vs. 0.7 cm·s -1 ·mmHg -1 , P=0.001 ). Among all clinical, demographic, and hemodynamic variables, only two (infarct volume, ipsilateral falling slope) significantly contributed to prediction of MLS (accuracy 94%; Figure 1B). Conclusions: This predictive model of MLS wields translatable potential for triaging level of care in patients suffering from LVO ischemic stroke, but further research, including optimization of the PPR algorithm as well as prospective use of the predictive model, is needed.

Introduction: Decreases in blood pressure (BP) during endovascular therapy (EVT) are associated with infarct progression and poor outcome. The largest BP reductions are thought to occur during induction. The frequency and clinical relevance of late BP decreases after partial reperfusion has been achieved remain unknown. In this study, we aimed to characterize the timing of BP reductions during EVT and to assess their association with functional outcome. Methods: We retrospectively studied patients with LVO stroke who underwent EVT at two comprehensive stroke centers. BP was continuously monitored throughout the procedure and averaged for selected time points. Maximum BP drop was calculated as the difference between admission systolic BP (SBP) and lowest SBP during EVT and assigned to one of three intervals: 1) arrival to angiography suite to groin puncture, 2) groin puncture to first pass, and 3) first pass to recanalization. Functional outcome was assessed using the modified rankin scale (mRS) at 90 days. Associations with the outcome were analyzed using ordinal logistic regression and adjusted for the size of the maximum drop in SBP. Results: 401 patients (age 71.3±14, 57% female, mean NIHSS 17) were included. Mean SBP for all patients decreased from EVT start to first procedural angiogram and then stabilized (Figure 1A). While the majority of blood pressure reductions occurred during interval 1 and 2 (n=253, 70%), 30% took place after first pass. We found no relation between timing of BP reduction and outcome (p=0.780, Figure 1B). Decreases in SBP during all intervals were significantly associated with 90-day outcome (OR per 10 mmHg 1.2, p=0.013; OR 1.1, p=0.025; and OR 1.3, p=0.011 for interval 1-3, respectively). Conclusions: BP drops occur throughout EVT, including between first pass and recanalization. Regardless of when these drops occur, they associate with poor outcome and thus underline the importance of blood pressure management throughout the procedure.

Introduction: Both increased blood pressure (BP) variability and impaired autoregulation have been associated with increased risk of poor outcome after endovascular thrombectomy (EVT). The combined effect of these two variables, however, has not yet been elucidated. We hypothesized that the detrimental effects of high BP variability may be amplified by impaired autoregulation. Methods: We prospectively enrolled patients with large-vessel occlusion (LVO) stroke undergoing EVT. Autoregulatory function was continuously measured for up to 48 hours post-EVT by interrogating changes in near-infrared spectroscopy-derived tissue oxygenation (a cerebral blood flow surrogate) in response to changes in BP (Fig. 1A). BP variability was assessed using the standard deviation of the mean. Values were averaged for the entire recording period and dichotomized based on the median. Functional outcome was assessed using the modified Rankin scale (mRS) at 90 days. We examined the association between BP variability, autoregulatory function, and outcome using ordinal logistic regression, adjusting for age and admission NIHSS. Results: Ninety-five patients (mean age 71, NIHSS 14, monitoring time 28±18 hours) were included. BP variability (p=0.043) and autoregulation (p=0.04) were each independently associated with functional outcome. Among patients with high BP variability, worse autoregulation was independently associated with higher (worse) mRS scores at 90 days (OR 3.9, 95% CI 1.1-14.5, p=0.036; Fig. 1B). The proportion of favorable outcome was highest among patients with low BP variability and better autoregulation, and lowest among those with high BP variability and worse autoregulation (p=0.073; Fig. 1C). Conclusion: For LVO stroke patients with high BP variability after EVT, worse functional outcome may be exacerbated by impaired autoregulation. These results suggest that autoregulatory status should be considered in the management of BP after EVT.

Introduction: Decreases in blood pressure (BP) during endovascular therapy (EVT) have been associated with infarct progression and worse outcome after large vessel occlusion (LVO) stroke. However, BP trajectories in the acute phase prior to EVT have not been well characterized. We thus used high-frequency BP and hemodynamic monitoring to create a continuous BP time trend and to determine timing of BP reductions. Methods: We prospectively enrolled patients with LVO stroke undergoing EVT. BP and cardiac hemodynamic variables were recorded every 20 seconds from emergency room admission until end of EVT using non-invasive finger plethysmography. Time trends of BP recordings were categorized into 4 windows: admission to imaging; imaging to EVT; EVT to groin puncture and groin puncture to recanalization. Episodes of hypotension (mean arterial pressure ≤ 70 mmHg) were correlated with administered medications and other potentially related interventions. Time trends in hemodynamic variables were analyzed using generalized estimating equations. Results: 25 patients underwent continuous BP monitoring (age 74±18; 68% female; mean NIHSS 12, monitoring time 8.34±2 hrs). Aggregated time series data revealed a marked BP reduction around time of imaging from which patients recovered (mean SBP 33 mmHg, duration 18 min, Fig A). A sustained decrease in BP was observed after groin puncture without return to baseline BP levels. In 62% of cases, reductions in BP were associated with BP lowering medications. A significant reduction in cardiac output (p=0.003) and increase in stroke volume variation (p=0.022) was seen across predetermined time points (Fig B & C). Conclusion: In patients with LVO, marked and frequently iatrogenic BP reductions occur around time of initial imaging and may present a potential target for intervention. Changes in cardiac hemodynamic variables throughout acute stroke period suggest a potential role for fluid resuscitation for hemodynamic optimization.

Objective: To evaluate results of concurrent tonsillectomy and adenoidectomy in the children. Materials and Methods: 82 patients were given concurrent tonsillectomy and adenoidectomy in the children from 4/2016 to 5/2017, and the results were studied by descriptive, prospective and clinical methods. Results: Average of operating time were 19.2 ± 4.2 minutes. Blood loss during the operations averaged 38.2 ± 4.1ml. Percent rate reduction of recurrent sore throat 96.3%, recurrent fever 89.0%, rhinorrhea 69.5%, nasal obstruction 88.9%, snoring sleep 63.4%, swallowing 30.5%. After surgery, 73.2% of the family members were very satisfied, 26.8% were satisfied with the results. Conclusion: Concurrent tonsillectomy and adenoidectomy, this saves on surgery costs, saves time, improves clinical symptoms, and pain levels are comparable to simple tonsillectomy. Key words: tonsillectomy, adenoidectomy

Background: This study aims to research clinical characteristics and to evaluate the results of early surgical treatment of infected preauricular sinus. Subjects and methods: Studied 46 patients (46 ears) sufferring from infected preauricular sinus surgically treated, by the method of descriptive observative prospective study with clinical intervention. Results: Age group of ≤ 15 years old accounted for the highest percentage with 71.8%. Combined defects accounted for 2.2%. Number of patients having familial factors accounted for 60.9%. Location of preauricular sinus: classic position 91.3%, posterior to classic position 8.7%. Positive bacteria culture with the proportion of 38.5%. Common bacterium was Staphylococcus aureus 60%. Most bacteria were sensitive to antibiotics. Stages of the infected preauricular sinus: inflammation 71.7%, abcess 48.5%. Surgical procedures: hot 69.6%, warm 30.4%. Average inpatient time: 8.5 ± 3.1 days. Recurrence after surgery 3 months having 1 ear, accounted for 2.2%. Results after surgery 3 months: good 91.3%, moderate 6.5%, bad 2.2%. Conclusions: Infected preauricular sinus were most common in children, combined defects were rare, having the role of family factors. Preauricular sinus having classic position occupied high percentage. Majority of postoperative results were good. Key words: Preauricular sinus

Background: Given the tolerability of nPG in first-line therapy, we desired to evaluate the response and toxicity profiles of second-line gemcitabine with nab-paclitaxel (nPG) following FOLFIRINOX. Methods: We retrospectively identified 30 patients who received first-line FOLFIRINOX for unresectable or metastatic pancreatic adenocarcinoma followed by second-line nPG. Response was evaluated by RECIST criteria and carbohydrate antigen 19-9 (CA19-9) change. Results: Median age was 63 years with 77% percent having metastatic disease. Nineteen patients (63%) achieved PR based on CA19-9. Median overall survival (OS) with nPG was 12.4 months (mo) and median progression-free survival (PFS) was 3.7 mo. Median PFS and OS for patients with at least stable CA19-9 were 4.7 and 13.9 mo since initiation of nPG. Patients with an increased CA19-9 level during nPG had a shorter median PFS (1.4 mo) and OS (5.3 mo). A significant PFS difference was demonstrated in patients with at least stable disease as the best RECIST response versus in those with progressive disease (5.4 vs. 1.9 mo, P Conclusions: This study demonstrates a clinical benefit of second-line nPG. The study also suggests a possible use of CA19-9 to predict response to therapy.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, with a 5-year survival of 8%. Current therapeutic regimens are largely ineffective and underscore the need for novel treatment strategies. Chromosomal rearrangements involving the anaplastic lymphoma kinase (ALK) gene have been identified in several neoplasms. In addition, ALK protein inhibitors have proven efficacy in patients with ALK-rearranged tumors. However, ALK translocations in PDAC have not been described. Through comprehensive genomic profiling of 3,170 PDACs, we identified 5 cases (0.16%) that harbored an ALK fusion gene: an exon 6 EML4-exon 20 ALK translocation (n=3), an exon 13 EML4-exon 20 ALK translocation (n=1), and an exon 3 STRN-exon 20 ALK translocation (n=1). Among the most prevalent PDAC-related genes, activating KRAS mutations were absent in all 5 cases, who were

Background The importation of SARS-CoV-2 through air travel poses substantial risks to generate new COVID-19 outbreaks. Timely contact tracing is particularly crucial to limit onwards transmission in settings without established community transmission. Methods We conducted an in-depth analysis of the response to a big flight-associated COVID-19 outbreak in Vietnam in March 2020 that involved contact tracing, systematic testing and strict quarantine up to third generation contacts. Results 183 primary contacts from the flight as well as 1000 secondary and 311 third generation contacts were traced, tested, and quarantined across 15 provinces across Vietnam. The protracted confirmation of the index case at 3 days and 19 h after arrival resulted in isolation/quarantine delays of 6.8 days (IQR 6.3–6.8) and 5.8 days (IQR 5.8–7.0) for primary and secondary cases, respectively, which generated 84.0 and 26.4 person-days of community exposure from primary and secondary cases, respectively. Nevertheless, only 5 secondary cases occurred. Conclusions A large flight-related COVID-19 cluster was successfully contained through timely, systematic and comprehensive public health responses despite delayed index case identification. Multiagency collaboration and pre-established mechanisms are crucial for low and middle income countries like Vietnam to limit community transmission after COVID-19 importation through air travel.

To assess the difference in time to and predictors of reintervention according to valve type in surgical bioprosthetic pulmonary valve replacement (PVR) in patients younger than 30 years of age from multiple centers.Data were retrospectively collected for 1278 patients30 years of age undergoing PVR at 8 centers between 1996 and 2015.Mean age at PVR was 19.3 ± 12.8 years, with 719 (56.3%) patients ≤18 years of age. Diagnosis was tetralogy of Fallot in 626 patients (50.5%) and 165 (12.9%) had previous PVR. Median follow-up was 3.9 years (interquartile range, 1.2, 6.4). Multiple valve types were used, most commonly CE PERIMOUNT, 488 (38.2%), CE Magna/Magna Ease, 361 (28.2%), and Sorin Mitroflow 322 (25.2). Reintervention occurred in 12.7% and was most commonly due to pulmonary stenosis (68.8%), with most reinterventions occurring in children (85.2%) and with smaller valve sizes (P .001) Among adults aged 18 to 30 years, younger age was not a significant risk factor for reintervention. Surgical indication of isolated pulmonary regurgitation was associated with a lower risk of reintervention (P .001). Overall, 1-, 3-, 5-, and 10-year freedom from reintervention rates were 99%, 97%, 92%, and 65%. The only independent risk factors for reintervention after controlling for age and valve size were lack of a concomitant tricuspid valve procedure (P = .02) and valve type (P .001); Sorin and St Jude valves were associated with similar time to reintervention, and deteriorated more rapidly than other valve types.In this large multicenter study, 8% of patients have undergone reintervention by 5 years. Importantly, independent of age and valve size, reintervention rates vary by valve type.

Based on described benefits of fast-tracking and early extubation in children undergoing congenital heart surgery, we applied this concept to selected children following uncomplicated orthotopic heart transplantation (OHT). In this case series, we report four patients who were extubated immediately after surgery in the operating room. A mild respiratory acidosis and hypercapnia were noted on the initial arterial blood gases, were well tolerated, and were normalized within 6 to 12 hours. There was no mortality among patients who were extubated in the operating room, and no patients required reintubation. We conclude that operating room extubation is feasible in selected patients undergoing OHT.

Height matching in pediatric HTx has been proposed as a superior method of evaluating graft size, but no studies have examined survival advantage for height-matched donor-recipient pairs. We hypothesized that in pediatric patients with DCM, an oversized donor improves survival and aimed to define the optimal height ratio in this patient group. Pediatric primary HTx recipients with DCM between 10/89 and 09/12 were identified in the OPTN database. Patients were stratified into three donor-recipient height and weight ratio categories. One- and five-yr survival was compared using Kaplan-Meier analysis and HRs were computed. A total of 2133 children with DCM who underwent HTx during the study period were included. Unadjusted one-yr survival was worse for DRHR

Background: Anomalous aortic origin of a coronary artery from the wrong Sinus of Valsalva (AAOCA) is a rare congenital anomaly and is associated with sudden cardiac death. Morphologic features considered to be “high risk” are significant luminal narrowing, acute coronary angulation at its origin, intramural course, and long interarterial course. A consistent approach for characterization of these features is lacking. Methods: A retrospective single-center review of all patients diagnosed with AAOCA using echocardiogram and computed tomography (CT)/magnetic resonance imaging (MRI) studies was performed. Twenty-nine patients were identified (25 using CT and 4 using MRI) with subsequent three-dimensional data sets. The MRI data sets lacked adequate resolution and were excluded. Twenty-five patients (median age 15.1, range 10-39.5 years, 72% male) were further analyzed using echocardiogram and CT. Morphologic assessment focused on luminal stenosis, coronary angulation, and interarterial length. Additional morphologic features focusing on cross-sectional area and degree of ellipticity were also assessed. Results: Echocardiography tended to yield smaller measurements compared to CT and had poor interobserver reproducibility for measurements pertaining to the narrowest proximal and distal coronary segments. Computed tomography showed good inter-/intraobserver reproducibility for the same. Agreement between both modalities for coronary angulation at its origin was excellent. There was good agreement for measurements of interarterial length between echocardiography and CT, but echocardiography had superior reproducibility. Assessment of luminal cross-sectional area and elliptical shape by CT had excellent inter-/intraobserver reproducibility. Conclusion: The combination of echocardiography and CT characterizes morphologic features of anomalous origin of the coronary artery more reliably than either modality alone.

Background Drug-induced nephrotoxicity in the form of acute kidney injury (AKI) is a potential adverse effect of vancomycin, which is commonly prescribed empirically with an antipseudomonal agent. It is unclear if combinations with certain antipseudomonal agents (e.g., piperacillin-tazobactam) are associated with more AKI relative to others. Methods This retrospective cohort study conducted at two Veterans Affairs (VA) Medical Centers with differing preferred empiric vancomycin-antipseudomonal regimens aimed to assess the incidence of AKI in patients receiving vancomycin and piperacillin-tazobactam (VPT) at VA Greater Los Angeles Healthcare System (HCS) versus vancomycin and cefepime (VC) at VA Long Beach HCS. Patients who received VPT or VC for at least 48 hours in 2016–2018 were included. AKI definitions were derived from 2012 Kidney Disease Improving Global Outcomes guidelines. Secondary assessments included hospital length of stay, 90-day mortality, and incidence of Clostridioides difficile infection (CDI) within 90 days. Patients who developed AKI were further assessed for time-to-onset of AKI, development of chronic kidney disease (CKD) within 90 days, and hemodialysis (HD) dependence within 1 year. Statistical analysis was performed using Fisher’s exact and Mann-Whitney U tests where appropriate. Propensity score matching using logistic regression with nearest-neighbor matching was performed to control for potential confounding baseline characteristics. Results 21/120 patients receiving VPT developed AKI vs. 4/120 receiving VC (17.5% vs. 3.3%, p=0.0005). After propensity score matching, AKI incidence remained significantly higher for VPT patients (15.2% vs. 4.0%, p=0.01). Median length of stay was significantly longer for VPT patients (10 days vs. 8 days, p=0.03). There was no significant difference in time-to-onset of AKI, 90-day mortality, or CDI. No significant difference was found in the development of CKD within 90 days nor the requirement of HD within 1 year. Conclusion VPT combination therapy was associated with increased incidence of AKI compared to VC, though 90-day mortality and other outcomes were similar. Advising prescribers about potentially increased risk of AKI with VPT is a viable stewardship intervention. Disclosures All Authors: No reported disclosures

Although the use of a right ventricle to pulmonary artery shunt as a source of pulmonary blood flow in stage 1 Norwood palliation is common, there is no uniform agreement on the optimal surgical technique. We present a technique for creating the distal connection aimed at minimizing procedural bleeding, promoting distal patency, and facilitating second-stage palliation.

Visual Abstract, Highlights • MCD inhibition decreases fatty acid oxidation via increasing malonyl coenzyme A levels to prevent fatty acid uptake into mitochondria in the failing hearts induced by coronary artery ligation. • Downregulating fatty acid oxidation by MCD inhibition occurrs in conjuction with a decrease in glycolysis and in proton production while an increase in triacylglycerol biosynthesis. • MCD inhibition enhances antioxidative capacity through increasing mitochondrial superoxide dismutase activity via reducing its acetylation., Summary Alterations in cardiac energy metabolism after a myocardial infarction contribute to the severity of heart failure (HF). Although fatty acid oxidation can be impaired in HF, it is unclear if stimulating fatty acid oxidation is a desirable approach to treat HF. Both immediate and chronic malonyl coenzyme A decarboxylase inhibition, which decreases fatty acid oxidation, improved cardiac function through enhancing cardiac efficiency in a post–myocardial infarction rat that underwent permanent left anterior descending coronary artery ligation. The beneficial effects of MCD inhibition were attributed to a decrease in proton production due to an improved coupling between glycolysis and glucose oxidation.

Our goal was to construct three-dimensional (3D) virtual models to allow simultaneous visualization of the ventricles, ventricular septal defect (VSD) and great arteries in patients with complex intracardiac anatomy to aid in surgical planning. We also sought to correlate measurements from the source cardiac magnetic resonance (CMR) image dataset and the 3D model. Complicated ventriculo-arterial relationships in patients with complex conotruncal malformations make preoperative assessment of possible repair pathways difficult. Patients were chosen with double outlet right ventricle for the complexity of intracardiac anatomy and potential for better delineation of anatomic spatial relationships. Virtual 3D models were generated from CMR 3D datasets. Measurements were made on the source CMR as well as the 3D model for the following structures: aortic diameter in orthogonal planes, VSD diameter in orthogonal planes and long axis of right ventricle. A total of six patients were identified for inclusion. The path from the ventricles to each respective outflow tract and the location of the VSD with respect to each great vessel was visualized clearly in all patients. Measurements on the virtual model showed excellent correlation with the source CMR when all measurements were included by Pearson coefficient, r = 0.99 as well as for each individual structure. Construction of virtual 3D models in patients with complex conotruncal defects from 3D CMR datasets allows for simultaneous visualization of anatomic relationships relevant for surgical repair. The availability of these models may allow for a more informed preoperative evaluation in these patients.