Examining patient-reported late toxicity and its association with quality of life and unmet need for symptom management among nasopharyngeal cancer survivors: a cross-sectional survey.

Introduction: Alongside the improved survival of nasopharyngeal cancer (NPC), late radiation toxicities are alarmingly hampering survivors' quality of life. A patient-reported symptom burden survey is lacking to address the unmet need for symptom management among local NPC survivors. Methods: A single-center cross-sectional survey was conducted on 211 NPC survivors who had completed radiation therapy for three to 120 months. We employed the Chinese version M. D. Anderson Symptom Inventory - Head & Neck Module (MDASI-HN-C), Functional Assessment of Cancer Therapy - Head & Neck (FACT-HN-C), and a question extracted from the Cancer Survivors' Unmet Needs Measure (CaSUN). Results: Two hundred valid responses were collected. Participants suffered from at least four moderate to severe symptoms (mean = 4.84, SD = 4.99). The top five severe symptoms were dry mouth, mucus problems, difficulty swallowing or chewing, teeth or gum problems, and memory problems. MDASI-HN-C subscales were negatively correlated with the physical, emotional, functional, and HN-specific domains of the FACT-HN-C. The unmet need for symptom management was positively associated with symptom burden, either general symptoms (Adjusted odds ratio [ORadj] = 1.566, 95% CI = 1.282 - 1.914, p < 0.001) or top-5 symptoms (ORadj = 1.379, 95% CI = 1.185 - 1.604, p < 0.001), while negatively associated with post-RT time (ORadj = 0.981, 95% CI [0.972, 0.991], p < 0.001). Conclusion: Virtually all NPC survivors suffer from late toxicities, which interplay with survivors' perceptions intricately to affect their unmet needs for symptom management. Personalized supportive care strategies with regular assessments and stratifications are warranted.

Predictive Factors for Chemoradiation-Induced Oral Mucositis and Dysphagia in Head and Neck Cancer: A Scoping Review.

Despite advances in head and neck cancer treatment, virtually all patients experience chemoradiation-induced toxicities. Oral mucositis (OM) and dysphagia are among the most prevalent and have a systemic impact on patients, hampering treatment outcome and harming quality of life. Accurate prediction of severe cases is crucial for improving management strategies and, ultimately, patient outcomes. This scoping review comprehensively maps the reported predictors and critically evaluates the performance, methodology, and reporting of predictive models for these conditions. A total of 174 studies were identified from database searches, with 73 reporting OM predictors, 97 reporting dysphagia predictors, and 4 reporting both OM and dysphagia predictors. These predictors included patient demographics, tumor classification, chemoradiotherapy regimen, radiation dose to organs-at-risk, genetic factors, and results of clinical laboratory tests. Notably, many studies only conducted univariate analysis or focused exclusively on certain predictor types. Among the included studies, numerous predictive models were reported: eight for acute OM, five for acute dysphagia, and nine for late dysphagia. The area under the receiver operating characteristic curve (AUC) ranged between 0.65 and 0.81, 0.60 and 0.82, and 0.70 and 0.85 for acute oral mucositis, acute dysphagia, and late dysphagia predictive models, respectively. Several areas for improvement were identified, including the need for external validation with sufficiently large sample sizes, further standardization of predictor and outcome definitions, and more comprehensive reporting to facilitate reproducibility.

Computed Tomography-Based Radiomics for Long-Term Prognostication of High-Risk Localized Prostate Cancer Patients Received Whole Pelvic Radiotherapy.

Given the high death rate caused by high-risk prostate cancer (PCa) (>40%) and the reliability issues associated with traditional prognostic markers, the purpose of this study is to investigate planning computed tomography (pCT)-based radiomics for the long-term prognostication of high-risk localized PCa patients who received whole pelvic radiotherapy (WPRT). This is a retrospective study with methods based on best practice procedures for radiomics research. Sixty-four patients were selected and randomly assigned to training (n = 45) and testing (n = 19) cohorts for radiomics model development with five major steps: pCT image acquisition using a Philips Big Bore CT simulator; multiple manual segmentations of clinical target volume for the prostate (CTVprostate) on the pCT images; feature extraction from the CTVprostate using PyRadiomics; feature selection for overfitting avoidance; and model development with three-fold cross-validation. The radiomics model and signature performances were evaluated based on the area under the receiver operating characteristic curve (AUC) as well as accuracy, sensitivity and specificity. This study's results show that our pCT-based radiomics model was able to predict the six-year progression-free survival of the high-risk localized PCa patients who received the WPRT with highly consistent performances (mean AUC: 0.76 (training) and 0.71 (testing)). These are comparable to findings of other similar studies including those using magnetic resonance imaging (MRI)-based radiomics. The accuracy, sensitivity and specificity of our radiomics signature that consisted of two texture features were 0.778, 0.833 and 0.556 (training) and 0.842, 0.867 and 0.750 (testing), respectively. Since CT is more readily available than MRI and is the standard-of-care modality for PCa WPRT planning, pCT-based radiomics could be used as a routine non-invasive approach to the prognostic prediction of WPRT treatment outcomes in high-risk localized PCa.

Physical, psychological, and behavioral problems among children and adolescents in countries with different economic statuses during the COVID-19 pandemic: a systematic review and meta-analysis.

Introduction: The COVID-19 pandemic has impacted children and adolescents' physical activity (PA), sleeping patterns, and psychological and behavioral health. Yet, little is known about the differences between those in countries with various economic statuses. Methods: Articles published from database inception through 16 March 2022 were retrieved using CINAHL Complete, Cochrane Library, EMBASE, Medline, PubMed, and PsycINFO. High-quality studies that reported the number of participants with parameters associated with PA, sleeping patterns, and psychological and behavioral problems in young people aged under 18 years during the pandemic were included. We referenced the Canadian 24-Hour Movement Guidelines for PA and sleep duration to provide the event rate for young people who were not compliant with the guidelines. The event rate of young people who had decreased sleep quality and experienced psychological and behavioral problems were also investigated. A subgroup analysis was conducted to identify the differences in those in countries with diverse economic statuses. Funnel plot analysis and Egger's test were also conducted to identify any risk of publication bias. Result: A total of 66 studies with 1,371,168 participants aged between 0 and 18 years, involving 27 countries, were included. During the pandemic, we identified that 41% (95% CI: 39%, 43%; I2 = 96.62) and 43% (95% CI: 34%, 52%; I2 = 99.42) of young people did not meet the PA and sleep duration recommendation guidelines. In addition, 31% (95% CI: 28%, 35%; I2 = 99.66) of young people had decreased their sleep quality. Yet, no significant difference was found across countries with different economic statuses. However, the event rates of participants with psychological and behavioral problems were 32% (95% CI: 28%, 36%; I2 = 99.85) and 19% (95% CI: 14%, 25%; I2 = 99.72), respectively. In addition, the rate of psychological problems was more severe in those who live in lower middle-income countries (p < 0.001), while the rate of behavioral problems was more severe in those who live in high-income countries (p = 0.001). Discussion: During the pandemic, the discouragement of PA, poor sleep quality, and high risk of psychological and behavioral problems are concerning. A large number of young people did not comply with the recommendation guidelines. Timely implementation of recovery plans is critical to address the adverse effects on young people. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=309209, identifier CRD42022309209.

Artificial intelligence-driven radiomics study in cancer: the role of feature engineering and modeling.

Modern medicine is reliant on various medical imaging technologies for non-invasively observing patients' anatomy. However, the interpretation of medical images can be highly subjective and dependent on the expertise of clinicians. Moreover, some potentially useful quantitative information in medical images, especially that which is not visible to the naked eye, is often ignored during clinical practice. In contrast, radiomics performs high-throughput feature extraction from medical images, which enables quantitative analysis of medical images and prediction of various clinical endpoints. Studies have reported that radiomics exhibits promising performance in diagnosis and predicting treatment responses and prognosis, demonstrating its potential to be a non-invasive auxiliary tool for personalized medicine. However, radiomics remains in a developmental phase as numerous technical challenges have yet to be solved, especially in feature engineering and statistical modeling. In this review, we introduce the current utility of radiomics by summarizing research on its application in the diagnosis, prognosis, and prediction of treatment responses in patients with cancer. We focus on machine learning approaches, for feature extraction and selection during feature engineering and for imbalanced datasets and multi-modality fusion during statistical modeling. Furthermore, we introduce the stability, reproducibility, and interpretability of features, and the generalizability and interpretability of models. Finally, we offer possible solutions to current challenges in radiomics research.

Integrating CT-based radiomic model with clinical features improves long-term prognostication in high-risk prostate cancer.

Objective: High-risk prostate cancer (PCa) is often treated by prostate-only radiotherapy (PORT) owing to its favourable toxicity profile compared to whole-pelvic radiotherapy. Unfortunately, more than 50% patients still developed disease progression following PORT. Conventional clinical factors may be unable to identify at-risk subgroups in the era of precision medicine. In this study, we aimed to investigate the prognostic value of pre-treatment planning computed tomography (pCT)-based radiomic features and clinical attributes to predict 5-year progression-free survival (PFS) in high-risk PCa patients following PORT. Materials and methods: A total of 176 biopsy-confirmed PCa patients who were treated at the Hong Kong Princess Margaret Hospital were retrospectively screened for eligibility. Clinical data and pCT of one hundred eligible high-risk PCa patients were analysed. Radiomic features were extracted from the gross-tumour-volume (GTV) with and without applying Laplacian-of-Gaussian (LoG) filter. The entire patient cohort was temporally stratified into a training and an independent validation cohort in a ratio of 3:1. Radiomics (R), clinical (C) and radiomic-clinical (RC) combined models were developed by Ridge regression through 5-fold cross-validation with 100 iterations on the training cohort. A model score was calculated for each model based on the included features. Model classification performance on 5-year PFS was evaluated in the independent validation cohort by average area-under-curve (AUC) of receiver-operating-characteristics (ROC) curve and precision-recall curve (PRC). Delong's test was used for model comparison. Results: The RC combined model which contains 6 predictive features (tumour flatness, root-mean-square on fine LoG-filtered image, prostate-specific antigen serum concentration, Gleason score, Roach score and GTV volume) was the best-performing model (AUC = 0.797, 95%CI = 0.768-0.826), which significantly outperformed the R-model (AUC = 0.795, 95%CI = 0.774-0.816) and C-model (AUC = 0.625, 95%CI = 0.585-0.665) in the independent validation cohort. Besides, only the RC model score significantly classified patients in both cohorts into progression and progression-free groups regarding their 5-year PFS (p< 0.05). Conclusion: Combining pCT-based radiomic and clinical attributes provided superior prognostication value regarding 5-year PFS in high-risk PCa patients following PORT. A large multi-centre study will potentially aid clinicians in implementing personalised treatment for this vulnerable subgroup in the future.

Deep Learning-Based Automatic Assessment of Radiation Dermatitis in Patients With Nasopharyngeal Carcinoma.

PURPOSE: Radiation dermatitis (RD) is a common, unpleasant side effect of patients receiving radiation therapy. In clinical practice, the severity of RD is graded manually through visual inspection, which is labor intensive and often leads to large interrater variations. To overcome these shortcomings, this study aimed to develop an automatic RD assessment based on deep learning (DL) techniques that could efficiently assist the RD severity classification in clinical application. METHODS AND MATERIALS: A total of 1205 photographs of the head and neck region were collected from patients with nasopharyngeal carcinoma (NPC) undergoing radiation therapy. The severity of RD in these photographs was graded by 5 qualified assessors based on the Radiation Therapy Oncology Group guidance. An end-to-end RD grading framework was developed by combining a DL-based segmentation network and a DL-based RD severity classifier, which are used for segmenting the neck region from the camera-captured photographs and grading, respectively. U-Net was used for segmentation and another convolutional neural network classifier (DenseNet-121) was applied to RD severity classification. Dice similarity coefficient was used to evaluate the performance of segmentation. Severity classification was evaluated by several metrics, including overall accuracy, precision, recall, and F1 score. RESULTS: Results of segmentation showed that the averaged dice similarity coefficients were 91.2% and 90.8% for front and side view, respectively. For RD severity classification, the overall accuracy of test photographs was 83.0%. Our method accurately classified 90.5% of grade 0, 67.2% of grade 1, 93.8% of grade 2, and 100% of above grade 2 cases. The overall prediction performance was comparable with human assessors. There was no significant difference in accuracy when using manually or automatically segmented regions (P = .683). CONCLUSIONS: We have successfully demonstrated a DL-based method for automatic assessment of RD severity in patients with NPC. This method holds great potential for efficient and effective assessing and monitoring of RD in patients with NPC.

Effects of Performing Applied Muscle Tension during Recovery after Phlebotomy in Young, First-Time Donors: A Pilot Study.

Vasovagal reaction (VVR) compromises donor safety and reduces the subsequent return rates. Performing applied muscle tension (AMT) during phlebotomy may reduce the incidence of VVR. However, the effectiveness of performing AMT after phlebotomy to reduce delayed VVR remains unclear. With ethics approval, 12 young, first-time donors (YFTD) were recruited to study the effects on stroke volume (SV), cardiac output (CO) and systemic vascular resistance (SVR) while performing AMT from needle insertion to end of recovery. Measurements from 12 matched control YFTD were used for comparison. Pre-donation anxiety and VVR severity were assessed. Compared to controls, donors who performed AMT had higher SV (Control: 57 mL vs. AMT: 69 mL, p = 0.045), higher CO (Control: 3.7 L·min-1 vs. AMT: 5.2 L·min-1, p = 0.006) and lower SVR (Control: 1962 dyn·s·cm-5 vs. AMT: 1569 dyn·s·cm-5, p = 0.032) during mid-phlebotomy. During recovery, the AMT group retained higher SV, higher CO and lower SVR than the control, but not reaching statistical significance. Practicing AMT during recovery resulted in sustained haemodynamic improvements beyond the donation period, despite the reduction in delayed VVR was insignificant compared to the control group. A larger sample size is needed to validate the effectiveness of performing AMT after donation to mitigate delayed VVR.

Rationale for Mass Masking in Controlling the COVID-19 Pandemic.

The rapid spread of the coronavirus disease 2019 (COVID-19) into a global pandemic caught the world unprepared. Previously effective measures for containing disease outbreaks were overwhelmed, necessitating strict controls such as lockdowns or curfews. Among the disease control interventions, community mass masking was one of the highly controversial issues with differing opinions on its indications or effectiveness from different health authorities around the world. Regions where community mass masking was timely introduced were associated with lower transmission rates, and more effective disease control. In this article, we discuss the evidence on the effectiveness, and rationale for community mass masking to prevent the COVID-19 transmission. Areas for further research to define the role of mass masking in light of the COVID-19 pandemic will be suggested. This would help policy makers in formulating mass masking policies.

Review on the Cellular Mechanisms of Low-Level Laser Therapy Use in Oncology.

Photobiomodulation (PBM) using low-level laser therapy (LLLT) is a treatment that is increasingly used in oncology. Studies reported enhancement of wound healing with reduction in pain, tissue swelling and inflammatory conditions such as radiation dermatitis, oral mucositis, and lymphedema. However, factors such as wavelength, energy density and irradiation frequency influence the cellular mechanisms of LLLT. Moreover, the effects of LLLT vary according to cell types. Thus, controversy arose as a result of poor clinical response reported in some studies that may have used inadequately planned treatment protocols. Since LLLT may enhance tumor cell proliferation, these will also need to be considered before clinical use. This review aims to summarize the current knowledge of the cellular mechanisms of LLLT by considering its effects on cell proliferation, metabolism, angiogenesis, apoptosis and inflammation. With a better understanding of the cellular mechanisms, bridging findings from laboratory studies to clinical application can be improved.

Norepinephrine or phenylephrine during spinal anaesthesia for Caesarean delivery: a randomised double-blind pragmatic non-inferiority study of neonatal outcome.

BACKGROUND: Norepinephrine is an effective vasopressor during spinal anaesthesia for Caesarean delivery. However, before it can be fully recommended, possible adverse effects on neonatal outcome should be excluded. We aimed to test the hypothesis that umbilical arterial cord pH is at least as good (non-inferior) when norepinephrine is used compared with phenylephrine for treatment of hypotension. METHODS: We enrolled 668 subjects having elective and non-elective Caesarean delivery under spinal or combined spinal-epidural anaesthesia in this randomised, double-blind, two-arm parallel, non-inferiority clinical trial. Arterial blood pressure was maintained using norepinephrine 6 µg ml-1 or phenylephrine 100 µg ml-1 according to the practice of the anaesthetist, either prophylactically or therapeutically, as an infusion or bolus. The primary outcome was umbilical arterial pH with a chosen non-inferiority margin of 0.01 units. RESULTS: Of 664 subjects (531 elective and 133 non-elective) who completed the study, umbilical arterial cord blood was analysed for 351 samples from 332 subjects in the norepinephrine group and 343 samples from 332 subjects in the phenylephrine group. Umbilical arterial pH was non-inferior in the norepinephrine group (mean, 7.289; 95% confidence interval [CI], 7.284-7.294) compared with the phenylephrine group (mean, 7.287; 95% CI, 7.281-7.292) (mean difference between groups, 0.002; 95% CI, -0.005 to 0.009; P=0.017). Subgroup analysis confirmed the non-inferiority of norepinephrine for elective cases but was inconclusive for non-elective cases. CONCLUSIONS: Norepinephrine was non-inferior to phenylephrine for neonatal outcome assessed by umbilical arterial pH. These results provide high-quality evidence supporting the fetal safety of norepinephrine in obstetric anaesthesia. CLINICAL TRIAL REGISTRATION: ChiCTR-IPR-15006235.

Performance evaluation of a portable bioimpedance cardiac output monitor for measuring hemodynamic changes in athletes during a head-up tilt test.

Cardiac output (CO) monitoring is useful for sports performance training, but most methods are unsuitable as they are invasive or hinder performance. The performance of PhysioFlow (PF), a portable noninvasive transthoracic bioimpedance CO monitor, was evaluated and compared with a reference Doppler CO monitor, USCOM, using a head-up tilt (HUT) test. With ethics committee approval, 20 healthy well-trained athletes were subjected to HUT in a fixed order of 0°, 70°, 30°, and 0° for 3 min each. Simultaneous hemodynamic measurements using PF and USCOM were made 30 s after a change in HUT and analyzed using t tests, ANOVA, and mountain plots. Heart rate (HR) and stroke volume (SV) from both monitors changed according to physiological expectation of tilt, but PF measurements of SV were higher with a positive bias (PF vs. USCOM, 0°: 87.3 vs. 54.0 mL, P < 0.001; 70°: 76.5 vs. 39.5 mL, P < 0.001; 30°: 81.4 vs. 50.1 mL, P < 0.001; 0°: 88.3 vs. 57.1 mL, P < 0.001). Relative changes in SV (∆SV) after each tilt measured using PF were lower with a negative bias (PF vs. USCOM, 0° to 70°: -12.3% vs. -26.3%, P = 0.002; 70° to 30°: +6.4% vs. +31.2%, P < 0.001; 30° to 0°: +9.2% vs. +15.8%, P = 0.280). CO measurements using PF at 70° were erroneous. Compared with USCOM, PF overestimated SV measurements but underestimated the ∆SV between HUT. Accuracy of the PF deteriorated at 70°, implying a gravitational influence on its performance. These findings suggested that the suitability of PF for sports use is questionable.NEW & NOTEWORTHY The use of impedance cardiography to monitor physiological changes in sports is rarely reported. Using head-up tilt test, we evaluated a portable noninvasive impedance cardiography device (PhysioFlow) by comparing it with a reference Doppler monitor (USCOM). Accuracy in tracking hemodynamic changes deteriorated with higher tilt, implying a gravitational influence on its performance. Stroke volume measurements were overestimated, but the changes were underestimated. Despite its convenient physical features, the suitability of PhysioFlow for sports use is questionable.

Haemodynamic responses of wearing low-pressure sports compression tights during an orthostatic challenge in healthy individuals.

OBJECTIVES: While previous studies have demonstrated an ergogenic effect of sport compression garments in exercise performance and recovery, the possible underlying mechanisms remain unclear. Claims for improved venous return from wearing sport compression garments with a low compression pressure remain unproven. The aim of this study was to determine the pressure profile exerted by low-pressure sports compression tights, and to investigate using a non-invasive Doppler ultrasound cardiac output monitor (USCOM), whether the compression applied will influence haemodynamic responses during an orthostatic challenge. DESIGN: A randomized-crossover design. METHODS: Thirty-three healthy participants (18 male and 15 female) underwent two trials, each consisting of lying supine and 70° head-up tilt wearing either a low-pressure sports compression tights (CT) or track pants (CON). Stroke volume (SV) and cardiac output (CO) were measured non-invasively using USCOM; heart rate (HR) and non-invasive blood pressure were measured, and systemic vascular resistance (SVR) was derived. RESULTS: The SV and CO was lower at 70° head-up tilt than in supine but wearing CT attenuated the decline in SV (25.9±11.6cm3 CT vs. 35.9±11.4cm3 CON, p<0.001), CO (1.1±0.7 Lmin-1 CT vs. 1.4±0.6 Lmin-1 CON, p<0.05), HR (8.8±8.4 beatmin-1 CT vs. 15.9±9.7 beatmin-1 CON, p<0.001) and SVR (740±504dscm-5 CT vs. 961±560dscm-5 CON, p<0.005). The mean arterial pressure (3.3±4.1mmHg CT vs. 3.6±4.5mm Hg CON, p>0.05) was similar in both trials. CONCLUSIONS: Healthy individuals wearing low-pressure sports compression tights experienced less severe haemodynamic disturbance such as decreases in CO, SV, HR and SVR during an orthostatic challenge.

Prophylactic Norepinephrine Infusion for Preventing Hypotension During Spinal Anesthesia for Cesarean Delivery.

BACKGROUND: The use of norepinephrine for maintaining blood pressure (BP) during spinal anesthesia for cesarean delivery has been described recently. However, its administration by titrated manually controlled infusion in this context has not been evaluated. METHODS: In a double-blinded, randomized controlled trial, 110 healthy women having spinal anesthesia for elective cesarean delivery were randomly allocated to 1 of 2 groups. In group 1, patients received an infusion of 5 µg/mL norepinephrine that was started at 30 mL/h (2.5 µg/min) immediately after intrathecal injection and then manually adjusted within the range 0-60 mL/h (0-5 µg/min), according to values of systolic BP measured noninvasively at 1-minute intervals until delivery, with the objective of maintaining values near baseline. In group 2, no prophylactic vasopressor was given, and a bolus of 1 mL norepinephrine 5 µg/mL (5 µg) was given whenever systolic BP decreased to <80% of the baseline value. The study protocol was continued until delivery. The primary outcomes of the study were the incidence of hypotension and the overall stability of systolic BP control versus baseline compared using performance error calculations. In addition, the incidence and timing of hypotension were further compared using survival analysis. RESULTS: Three patients were excluded from the analysis. Nine patients (17%) in group 1 had 1 or more episodes of hypotension versus 35 (66%) in group 2 (P < .001). Performance error calculations showed that on average, systolic BP was maintained closer to baseline (P < .001) in group 1. Survival curve analysis showed a significant difference between groups (log-rank test P < .001). Four patients in each group had a recorded heart rate <60 beats/min (P = .98). Despite a much greater rate of administration of norepinephrine in group 1 (median, 61.0 [interquartile range, 47.0-72.5] µg) versus group 2 (5.0 [0-18.1] µg) (P < .001), there was no difference in neonatal outcome as assessed by Apgar scores and umbilical cord blood gas analysis. CONCLUSIONS: In patients having spinal anesthesia for elective cesarean delivery, a manually titrated infusion of 5 µg/mL of norepinephrine was effective for maintaining BP and decreasing the incidence of hypotension, with no detectable detrimental effect on neonatal outcome. Further investigation of the use of dilute norepinephrine infusions for routine use in obstetric patients is suggested.

Closed-Loop Feedback Computer-Controlled Phenylephrine for Maintenance of Blood Pressure During Spinal Anesthesia for Cesarean Delivery: A Randomized Trial Comparing Automated Boluses Versus Infusion.

BACKGROUND: We previously described the use of closed-loop feedback computer-controlled infusion of phenylephrine for maintaining blood pressure (BP) during spinal anesthesia for cesarean delivery. In this study, we report a modified system in which phenylephrine is delivered by intermittent boluses rather than infusion. We hypothesized that the use of computer-controlled boluses would result in more precise control of BP compared with infusions. METHODS: Two hundred fourteen healthy patients having spinal anesthesia for elective cesarean delivery were randomized to have their systolic BP maintained by phenylephrine administered by computer-controlled continuous infusion or computer-controlled intermittent boluses. From induction of anesthesia until the time of uterine incision, a noninvasive BP monitor was set to cycle at 1-minute intervals. In the infusion group, the infusion rate was automatically adjusted after each BP measurement using a previously described algorithm. In the bolus group, the algorithm was modified so that the mass of drug that would have been delivered over 1 minute was instead injected as a rapid intravenous bolus after each BP measurement. The precision of BP control was assessed using performance error calculations and compared between groups, with the primary outcome defined as median absolute performance error, and the latter being a measure of inaccuracy showing an average of the magnitudes of the differences of measured BP values above or below the target values. RESULTS: The precision of BP control was greater, as shown by smaller values for median absolute performance error, in the bolus group (median 4.38 [quartiles 3.22, 6.25] %) versus the infusion group (5.39 [4.12, 7.04] %, P = .008). In the bolus group, phenylephrine consumption was smaller; this was associated with smaller values for median performance error compared with the continuous infusion group (P < .001), which indicates that values for systolic BP, averaged over time, were slightly lower in the bolus group. There were no differences in cardiac output, nausea or vomiting, or neonatal outcome between groups. CONCLUSIONS: We confirmed the hypothesis that BP control was more precise when computer-controlled phenylephrine was delivered using intermittent boluses rather than continuous infusion. However, the difference between groups was small and was not associated with any difference in clinical outcomes. In the infusion group, greater doses of phenylephrine were delivered, which was related to the time taken for the noninvasive BP monitor to complete measurements. The use of intermittent boluses may be a useful alternative in the design of closed-loop vasopressor systems.

A longitudinal evaluation of early anatomical changes of parotid gland in intensity modulated radiotherapy of nasopharyngeal carcinoma patients with parapharyngeal space involvement.

INTRODUCTION: Radiotherapy of nasopharyngeal carcinoma patients with parapharyngeal space (PPS) involvement may deliver high dose to the parotid gland. This study evaluated parotid gland changes during and up to 3 months after radiotherapy. METHODS: Kilovoltage computed tomography (CT) scans of head and neck region of 39 nasopharyngeal carcinoma patients with PPS involvement were performed at pre-radiotherapy, 10th, 20th and 30th fractions and 3 months after treatment. The parotid glands were contoured in pre-radiotherapy planning CT scan and in subsequent scans. Dice similarity coefficient (DSC), percentage volume change and centroid movement between the planning CT and the subsequent CTs were obtained from the contouring software. In addition, the distance between medial and lateral borders of parotid glands from the mid-line at various time intervals were also measured. RESULTS: The ipsilateral parotid gland received a mean dose of about 5 Gy higher than the contralateral side. The mean DSC and parotid volume decreased by more than 30% at 20th fraction and reached the minimum at 30th fraction. Partial recovery was observed at 3 months after treatment. The centroid displacement followed a similar pattern, which moved medially and superiorly by an average of 0.30 cm and 0.18 cm, respectively, at 30th fraction. The changes in ipsilateral gland were slightly greater than the contralateral side. CONCLUSIONS: Substantial volume change and medial movement of parotid gland were observed with slightly greater magnitude in the ipsilateral side. Adaptive radiotherapy was suggested at around 15th to 20th fraction so as to optimise the original dose distribution of the plan.

The effect of head up tilting on bioreactance cardiac output and stroke volume readings using suprasternal transcutaneous Doppler as a control in healthy young adults.

To compare the performance of a bioreactance cardiac output (CO) monitor (NICOM) and transcutaneous Doppler (USCOM) during head up tilting (HUT). Healthy young adult subjects, age 22 ± 1 years, 7 male and 7 female, were tilted over 3-5 s from supine to 70° HUT, 30° HUT and back to supine. Positions were held for 3 min. Simultaneous readings of NICOM and USCOM were performed 30 s into each new position. Mean blood pressure (MBP), heart rate (HR), CO and stroke volume (SV), and thoracic fluid content (TFC) were recorded. Bland-Altman, percentage changes and analysis of variance for repeated measures were used for statistical analysis. Pre-tilt NICOM CO and SV readings (6.1 ± 1.0 L/min and 113 ± 25 ml) were higher than those from USCOM (4.1 ± 0.6 L/min and 77 ± 9 ml) (P < 0.001). Bland-Altman limits of agreement for CO were wide with a percentage error of 38 %. HUT increased MBP and HR (P < 0.001). CO and SV readings decreased with HUT. However, the percentage changes in USCOM and NICOM readings did not concur (P < 0.001). Whereas USCOM provided gravitational effect proportional changes in SV readings of 23 ± 15 % (30° half tilt) and 44 ± 11 % (70° near full tilt), NICOM changes did not being 28 ± 10 and 33 ± 11 %. TFC decreased linearly with HUT. The NICOM does not provide linear changes in SV as predicted by physiology when patients are tilted. Furthermore there is a lack of agreement with USCOM measurements at baseline and during tilting.

Randomized double-blinded comparison of norepinephrine and phenylephrine for maintenance of blood pressure during spinal anesthesia for cesarean delivery.

BACKGROUND: During spinal anesthesia for cesarean delivery, phenylephrine can cause reflexive decreases in maternal heart rate and cardiac output. Norepinephrine has weak ß-adrenergic receptor agonist activity in addition to potent α-adrenergic receptor activity and therefore may be suitable for maintaining blood pressure with less negative effects on heart rate and cardiac output compared with phenylephrine. METHODS: In a randomized, double-blinded study, 104 healthy patients having cesarean delivery under spinal anesthesia were randomized to have systolic blood pressure maintained with a computer-controlled infusion of norepinephrine 5 µg/ml or phenylephrine 100 µg/ml. The primary outcome compared was cardiac output. Blood pressure heart rate and neonatal outcome were also compared. RESULTS: Normalized cardiac output 5 min after induction was greater in the norepinephrine group versus the phenylephrine group (median 102.7% [interquartile range, 94.3 to 116.7%] versus 93.8% [85.0 to 103.1%], P = 0.004, median difference 9.8%, 95% CI of difference between medians 2.8 to 16.1%). From induction until uterine incision, for norepinephrine versus phenylephrine, systolic blood pressure and stroke volume were similar, heart rate and cardiac output were greater, systemic vascular resistance was lower, and the incidence of bradycardia was smaller. Neonatal outcome was similar between groups. CONCLUSIONS: When given by computer-controlled infusion during spinal anesthesia for cesarean delivery, norepinephrine was effective for maintaining blood pressure and was associated with greater heart rate and cardiac output compared with phenylephrine. Further work would be of interest to confirm the safety and efficacy of norepinephrine as a vasopressor in obstetric patients.

High-resolution profiling of fetal DNA clearance from maternal plasma by massively parallel sequencing.

BACKGROUND: With the advent of massively parallel sequencing (MPS), DNA analysis can now be performed in a genomewide manner. Recent studies have demonstrated the high precision of MPS for quantifying fetal DNA in maternal plasma. In addition, paired-end sequencing can be used to determine the size of each sequenced DNA fragment. We applied MPS in a high-resolution investigation of the clearance profile of circulating fetal DNA. METHODS: Using paired-end MPS, we analyzed serial samples of maternal plasma collected from 13 women after cesarean delivery. We also studied the transrenal excretion of circulating fetal DNA in 3 of these individuals by analyzing serial urine samples collected after delivery. RESULTS: The clearance of circulating fetal DNA occurred in 2 phases, with different kinetics. The initial rapid phase had a mean half-life of approximately 1 h, whereas the subsequent slow phase had a mean half-life of approximately 13 h. The final disappearance of circulating fetal DNA occurred at about 1 to 2 days postpartum. Although transrenal excretion was involved in the clearance of circulating fetal DNA, it was not the major route. Furthermore, we observed significant changes in the size profiles of circulating maternal DNA after delivery, but we did not observe such changes in circulating fetal DNA. CONCLUSIONS: MPS of maternal plasma and urinary DNA permits high-resolution study of the clearance profile of circulating fetal DNA.