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Abstract Sepsis, one of the leading causes of death, is still lacking specific treatment. OXIRIS (BAXTER, Deerfield, IL, USA) is the first device allowing combined removal of endotoxins, inflammatory mediators and uremic toxins, alongside fluid balance control. Available data is very limited. This retrospective propensity score-matched cohort study of adult patients with septic shock aimed to evaluate septic shock duration and mortality in patients treated with either standard of care renal replacement therapy (RRT) or RRT with combined hemoadsorption, who were admitted to the interdisciplinary surgical intensive care unit at Heidelberg University Hospital during the years 2018 through 2021. Main outcomes were duration of shock, thirty-day mortality and plasma interleukin-6 levels before and after initiation of hemoadsorption. Included were 117 patients (female, 33%; male 67%); median age: 67 (16) years. After matching: 42 patients (female, 33%; male, 67%); mean age: 59.1 ± 13.8 years. There was no statistically significant difference in septic shock duration (p = 0.94; hazard ratio (HR) 0.97 (95% CI, 0.48–1.97)). Thirty-day survival analysis showed a non-statistically significant survival difference. (p = 0.063; HR 0.43 (95% CI, 0.17–1.09)). A post-hoc 90-day survival analysis revealed statistically significant longer survival and lower death hazard ratio in patients treated with RRT + HA (p = 0.037; HR = 0.42 (95% CI, 0.18–0.99). In conclusion, RRT with combined hemoadsorption of endotoxins, inflammatory mediators and uremic toxins is a modality worth further investigation.

BackgroundRadioembolization with yttrium-90 (Y-90) is utilized to treat primary liver malignancies. The efficacy of this intra-arterial therapy in arterially hypoperfused tumors is not known.MethodsWe reviewed data of patients with primary liver tumors treated with Y-90 prescription doses of at least 150 Gy. Baseline patient characteristics, treatment history, imaging-based tumor response assessments, and clinical outcome metrics were recorded. Tumors were classified as arterially hyperperfused versus hypoperfused on post-TARE Y-90 SPECT/CTs or pre-TARE hepatic perfusion SPECT/CTs. Perfusion status was correlated with tumor response assessments and clinical outcomes. Cox proportional hazards models were utilized to compare survival and progression-free survival. Inverse probability weighting was utilized to account for clinical factors and adjusted multivariable proportional hazards analyses to examine the relationship of quantitative perfusion and cancer outcomes.ResultsOf 400 Y-90 treatments, 88 patients received a prescribed dose of at least 150 Gy and had pre- or post-treatment SPECT/CT images. 11 and 77 patients had arterially hypoperfused and hyperperfused lesions, respectively. On dedicated liver MRI or CT at 3 months after Y-90, the complete response rates were 5.6% and 16.5% in the hypoperfused and hyperperfused cohort, respectively (P = 0.60). When controlling for various clinical features, including tumor histology, patients with arterially hypoperfused tumors had significantly shorter progression-free survival (HR 1.87, 95% CI - 1.03 - 3.37, P = 0.039) and greater elsewhere liver (HR 3.36, 95% CI = 1.23 - 9.20, P = 0.019) and distant failure (HR 7.64 (2.71 - 21.54, P < 0.001). In inverse probability weighted analysis, patients with arterially hypoperfused tumors had worse overall survival (P = 0.032). In the quantitative analysis, lower levels of lesion perfusion were also associated with worse clinical outcomes, again controlling for tumor histology.ConclusionCompared to arterially hyperperfused tumors, hypoperfused primary liver tumors treated with Y-90 may have worse clinical outcomes.

Objectives Multiple common cancers benefit from immunotherapy; however, less is known about efficacy in rare tumors. We report the results of the adrenocortical carcinoma cohort of NCI/SWOG S1609 Dual Anti-CTLA-4 and Anti-PD-1 blockade in Rare Tumors.Design/setting A prospective, phase 2 clinical trial of ipilimumab plus nivolumab was conducted by the SWOG Early Therapeutics and Rare Cancers Committee for multiple rare tumor cohorts across >1,000 National Clinical Trial Network sites.Participants 21 eligible patients were registered. Median age was 53 years (range 26–69); 16 (76%) were women.Interventions Ipilimumab 1 mg/kg intravenously every 6 weeks with nivolumab 240 mg intravenously every 2 weeks was administered until disease progression, symptomatic deterioration, treatment delay for any reason >56 days, unacceptable or immune-related toxicity with inability to decrease prednisone to 6 months), progression-free survival (PFS), overall survival (OS), and toxicity. Immune-related outcomes included immune ORR (iORR), immune CBR (iCBR), and immune PFS (iPFS). A two-stage design was used assuming: null=5% alternative=30%, n=6 in the first stage, 16 max, one-sided alpha=13%.Results The median number of prior therapy lines was 2 (range: 1–9). 3 of 21 patients attained confirmed partial response (PR) (ORR=14%). In addition, one patient had an unconfirmed PR; one, stable disease (SD)>6 months; one, immune-related RECIST (iRECIST) PR (iPR); and one patient attained iSD>6 months: clinical benefit rate (response or SD>6 months)=5/21 (24%), iORR=4/21 (19%), iCBR=7/21 (33%). The 6-month PFS was 24%; 6-month iPFS, 33%. The PFS for patients (N=7) with iRECIST clinical benefit were 57, 52, 18, 15, 13, 7, and 7 months. The 6-month OS was 76%; the median OS, was 15.8 months. The most common toxicities were fatigue (62%) and rash (38%), and the most common grade 3/4 immune-related adverse events were hepatic dysfunction (9.5%) and adrenal insufficiency (9.5%). Treatment-related adverse events leading to discontinuation of therapy in four patients (21%). There were no grade 5 adverse events.Conclusions Ipilimumab plus nivolumab is active in refractory metastatic adrenocortical cancer meeting the primary endpoint of the study, with a 19% iORR and 33% iCBR (includes SD/iSD>6 months) and with the longest PFS/iPFS of 52 and 57 months.Trial registration number NCT02834013 (registered 15 July, 2016; https://clinicaltrials.gov/ct2/show/NCT02834013).

Abstract Organic electrochemical transistors (OECTs) are ideal devices for translating biological signals into electrical readouts and have applications in bioelectronics, biosensing, and neuromorphic computing. Despite their potential, developing programmable and modular methods for living systems to interface with OECTs has proven challenging. Here we describe hybrid OECTs containing the model electroactive bacterium Shewanella oneidensis that enable the transduction of biological computations to electrical responses. Specifically, we fabricated planar p-type OECTs and demonstrated that channel de-doping is driven by extracellular electron transfer (EET) from S. oneidensis. Leveraging this mechanistic understanding and our ability to control EET flux via transcriptional regulation, we used plasmid-based Boolean logic gates to translate biological computation into current changes within the OECT. Finally, we demonstrated EET-driven changes to OECT synaptic plasticity. This work enables fundamental EET studies and OECT-based biosensing and biocomputing systems with genetically controllable and modular design elements.

Abstract Background Cardiovascular diseases (CVDs) are the leading cause of death around the world. Most CVDs-related death can be prevented by the optimal management of risk factors such as unhealthy diet and physical inactivity. Clinical practice guidelines (CPGs) for CVDs, provide some evidence-based recommendations which help healthcare professionals to achieve the best care for patients with CVDs. This systematic review aims to appraise the methodological quality of CPGs systematically and summarize the recommendations of self-managed non-pharmacological interventions for the prevention and management of CVDs provided by the selected guidelines. Methods A comprehensive electronic literature search was conducted via six databases (PubMed, Medline, The Cochrane Library, Embase, CINAHL, and Web of Science), seven professional heart association websites, and nine guideline repositories. The Appraisal of Guidelines, Research and Evaluation II (AGREE II) instrument was adopted to critically appraise the methodological quality of the selected guidelines. Content analysis was used to summarise recommended self-managed non-pharmacological interventions for CVDs. Results Twenty-three CPGs regarding different CVDs were included, in which four guidelines of CVDs, three for coronary heart diseases, seven for heart failure, two for atrial fibrillation, three for stroke, three for peripheral arterial disease, and one for hypertrophic cardiomyopathy. Twenty CPGs were appraised as high quality, and three CPGs as moderate quality. All twenty-three CPGs were recommended for use with or without modification. The domain of “Editorial Independence” had the highest standardized percentage (93.47%), whereas the domain of “Applicability” had the lowest mean domain score of 75.41%. The content analysis findings summarised some common self-managed non-pharmacological interventions, which include healthy diet, physical activity, smoking cessation, alcohol control, and weight management. Healthy diet and physical acidity are the most common and agreed on self-managed interventions for patients with CVDs. There are some inconsistencies identified in the details of recommended interventions, the intervention itself, the grade of recommendation, and the supported level of evidence. Conclusion The majority of the summarized non-pharmacological interventions were strongly recommended with moderate to high-quality levels of evidence. Healthcare professionals and researchers can adopt the results of this review to design self-managed non-pharmacological interventions for patients with CVDs.

(1) Background: Gastric cancer is a significant cause of cancer-related mortality worldwide. Weight loss and malnutrition associated with cancer are linked with increased mortality rates and reduced quality of life. Cancer cachexia, characterised by the loss of skeletal muscle, is associated with approximately 20% of cancer-related deaths and differs from malnutrition in that it cannot be fully reversed by nutritional support alone. It is now recognised that the primary pathophysiological process underlying cancer cachexia is chronic inflammation leading to increased calorie consumption. Current treatments that focus on nutritional supplementation, psychological counselling, appetite stimulation and reducing inflammation are lacking in efficacy. This review focuses on the evidence supporting the potential roles of natural anti-inflammatory products and their derivatives including fatty acids, probiotics, amino acids, curcumin, fucoidan, epigallocatechin-3-gallate, ginger, resveratrol and Boswellia serrata in the management of gastric cancer cachexia. (2) Results: While natural anti-inflammatory products show promise in a number of in vitro and in vivo studies, there are only a small number of human studies available. Where present, the evidence base is heterogeneous, with varying study methodologies and outcomes. (3) Conclusions: Natural anti-inflammatory products represent a potential adjunctive therapy for gastric cancer cachexia. Further research, particularly well-designed clinical trials, is needed to elucidate their optimal role, dosing and safety profiles in the management of gastric cancer cachexia.

Active lupus nephritis (LN) in pregnancy is strongly associated with poor maternal and fetal outcomes and, therefore, has implications on the planning, timing, and management. Prepregnancy evaluation is essential for all LN patients with childbearing potential to ensure pregnancies proceed in a safe and timely manner. Both maternal and fetal risks are communicated to patient during the evaluation. Stratification into different risk profile groups is then made based on disease activity and organ impairment severity. Patients with LN are generally divided into 3 main groups. Patients with LN who become pregnant receive treatments that are nonteratogenic and optimal for fetal and maternal outcomes. Throughout the pregnancy period, these patients are monitored closely under surveillance by a multidisciplinary team of clinicians. The management of patients with LN in pregnancy can be challenging both diagnostically (distinguishing LN from pre-eclampsia and determining the role and timing of kidney biopsy) and therapeutically (LN flares during pregnancy and managing a newly diagnosed LN during pregnancy).

Stroke is a major cause of death and disability globally, with ischemic stroke being the predominant mechanism. While spontaneous recanalization may occur, significant neuronal injury would have occurred in the interim. Intravenous thrombolysis administered within the first 4.5 h after stroke onset and endovascular thrombectomy within 24 h in patients with a salvageable penumbra improves functional independence. Ultrasound has been shown in both in vivo and in vitro models to enhance clot lysis, even more-so in the presence of thrombolytic agents. The use of transcranial Doppler and transcranial color-coded Doppler ultrasound in acute IS has been reported in case series, case-controlled studies, and clinical trials. While ultrasound at a frequency of 300 kHz increases the risk of intracranial hemorrhage, the 2 MHz range ultrasound aids thrombolysis and improves recanalization without significantly increasing the risk of symptomatic intracranial hemorrhage. Despite this, functional independence was not increased in clinical trials, nor was a benefit shown with the adjunctive use of microbubbles or microspheres. Nonetheless, newer technologies such as endovascular ultrasound, endovascular delivery of microbubbles, and thrombolytic-filled microbubbles await clinical trials. More evidence is needed before sonothrombolysis can be routinely used in the hyperacute management of ischemic stroke.

Background/Aims Non-alcoholic fatty liver disease (NAFLD) is associated with the development of cardiovascular disease. While existing studies have examined cardiac remodeling in NAFLD, there has been less emphasis on the development of carotid atherosclerosis and stroke. We sought to conduct a meta-analysis to quantify the prevalence, risk factors, and degree of risk increment of carotid atherosclerosis and stroke in NAFLD. Methods Embase and Medline were searched for articles relating to NAFLD, carotid atherosclerosis, and stroke. Proportional data was analysed using a generalized linear mixed model. Pairwise meta-analysis was conducted to obtain odds ratio or weighted mean difference for comparison between patients with and without NAFLD. Results From pooled analysis of 30 studies involving 7,951 patients with NAFLD, 35.02% (95% confidence interval [CI], 27.36–43.53%) had carotid atherosclerosis with an odds ratio of 3.20 (95% CI, 2.37–4.32; P

Abstract Background Dehydroepiandrosterone (DHEA) is a precursor sex hormone with antifibrotic properties. The aims of this study were to investigate antifibrotic mechanisms of DHEA, and to determine the relationship between DHEA-sulfate (DHEAS) plasma levels, disease severity and survival in patients with fibrotic interstitial lung diseases (ILDs). Methods Human precision cut lung slices (PCLS) and normal human lung fibroblasts were treated with DHEA and/or transforming growth factor (TGF)-β1 before analysis of pro-fibrotic genes and signal proteins. Cell proliferation, cytotoxicity, cell cycle and glucose-6-phosphate dehydrogenase (G6PD) activity were assessed. DHEAS plasma levels were correlated with pulmonary function, the composite physiologic index (CPI), and time to death or lung transplantation in a derivation cohort of 31 men with idiopathic pulmonary fibrosis (IPF) and in an independent validation cohort of 238 men and women with fibrotic ILDs. Results DHEA decreased the expression of pro-fibrotic markers in-vitro and ex-vivo. There was no cytotoxic effect for the applied concentrations, but DHEA interfered in proliferation by modulating the cell cycle through reduction of G6PD activity. In men with IPF (derivation cohort) DHEAS plasma levels in the lowest quartile were associated with poor lung function and higher CPI (adjusted OR 1.15 [95% CI 1.03–1.38], p = 0.04), which was confirmed in the fibrotic ILD validation cohort (adjusted OR 1.03 [95% CI 1.00–1.06], p = 0.01). In both cohorts the risk of early mortality was higher in patients with low DHEAS levels, after accounting for potential confounding by age in men with IPF (HR 3.84, 95% CI 1.25–11.7, p = 0.02), and for age, sex, IPF diagnosis and prednisone treatment in men and women with fibrotic ILDs (HR 3.17, 95% CI 1.35–7.44, p = 0.008). Conclusions DHEA reduces lung fibrosis and cell proliferation by inducing cell cycle arrest and inhibition of G6PD activity. The association between low DHEAS levels and disease severity suggests a potential prognostic and therapeutic role of DHEAS in fibrotic ILD.

Objectives To identify the barriers and enablers to implementing clinical practice guidelines (CPGs) recommendations in primary care and to provide recommendations that could facilitate the uptake of CPGs recommendations.Design An overview of systematic reviews.Data sources Nine electronic databases (PubMed, Cochrane Library, CINAHL, MEDLINE, PsycINFO, Web of Science, Journals @Ovid Full Text, EMBase, JBI) and three online data sources for guidelines (Turning Research Into Practice, the National Guideline Clearinghouse and the National Institute for Health and Care Excellence) were searched until May 2021.Eligibility criteria Systematic reviews, meta-analyses or other types of systematic synthesis of quantitative, qualitative or mixed-methods studies on the topic of barriers and/or enablers for CPGs implementation in primary care were included.Data extraction and synthesis Two authors independently screened the studies and extracted the data using a predesigned data extraction form. The methodological quality of the included studies was appraised by using the JBI Critical Appraisal Checklist for Systematic Reviews and Research Syntheses. Content analysis was used to synthesise the data.Results Twelve systematic reviews were included. The methodological quality of the included reviews was generally robust. Six categories of barriers and enablers were identified, which include (1) political, social and culture factors, (2) institutional environment and resources factors, (3) guideline itself related factors, (4) healthcare provider-related factors, (5) patient-related factors and (6) behavioural regulation-related factors. The most commonly reported barriers within the above-mentioned categories were suboptimal healthcare networks and interprofessional communication pathways, time constraints, poor applicability of CPGs in real-world practice, lack of knowledge and skills, poor motivations and adherence, and inadequate reinforcement (eg, remuneration). Presence of technical support (‘institutional environment and resources factors’), and timely education and training for both primary care providers (PCPs) (‘healthcare provider-related factors’) and patients (‘patient-related factors’) were the frequently reported enablers.Conclusion Policy-driven strategies should be developed to motivate different levels of implementation activities, which include optimising resources allocations, promoting integrated care models, establishing well-coordinated multidisciplinary networks, increasing technical support, encouraging PCPs and patients’ engagement in guideline development, standardising the reporting of guidelines, increasing education and training, and stimulating PCPs and patients’ motivations. All the activities should be conducted by fully considering the social, cultural and community contexts to ensure the success and sustainability of CPGs implementation.

Abstract Along with the increasing of infections of COVID‐19, nurses are needed more in caring patients with COVID‐19. The aim of this study is to explore the real intention and influencing factors of the nurses' willingness to participate in public health emergency in facing the COVID‐19. A total of 10 nurses who volunteered to care patients with COVID‐19 were selected. Data were collected by semi‐structured interviews and analyzed by content analysis method based on the theory of planned behavior. Three main categories were attitude, subjective norms and perceived behavior control. Under the first category, two subcategories were included: nurses' personal and professional value expectation, patriotism. Two subcategories were yielded for the second category: support from family and friends, role model impact of important people. In addition, three subcategories were identified for the third category: physical condition, professional knowledge and skills, national measures and incentive policies. Nurses with high willingness have seven features: high value expectation, patriotism, generous family support, good physical condition, experienced professional knowledge and skills, awareness of national measures and incentive policies. Combined with our previous quantitative study, developing tailored training programs to improve nurses’ professional value expectation, knowledge and skills in coping with unwilling attitude and weak perceived behavior control are effective ways.

Introduction Chronic pain is a common symptom significantly affecting the quality of life of breast cancer survivors. Despite the achievement of pharmacological interventions, the barriers associated with this approach such as inaccessibility, misuse and side effects drive research into effective non-pharmacological interventions to improve chronic pain management, quality of life, anxiety and depression. Breathing exercise (BE) can be a promising option, but research evidence is sparse. This pilot study aims to examine the feasibility and preliminary effect of using an evidence-based BE intervention for chronic pain management in breast cancer survivors.Method and analysis This study will be a two-parallel-arm, open-labelled, phase II randomised controlled trial with 1:1 allocation. Seventy-two participants will be recruited from a tertiary hospital in China and randomly allocated to either a BE intervention group (n=36) or a control group (n=36). The participants in the intervention group will receive the usual care, a pain information booklet and a 4-week self-administered BE intervention; the participants in the control group will receive the usual care and the pain information booklet only. The assessment will be conducted at three time points: baseline (week 0), immediately after the intervention completion (week 5) and 4 weeks after the intervention completion (week 9). The primary outcomes will be the acceptability and feasibility assessment of the study protocol and methodological procedures. The secondary outcomes will be the effects of BE on pain, quality of life, anxiety and depression in breast cancer survivors. Descriptive statistics will be applied to present the primary outcomes and the Generalised Estimating Equation Model will be utilised to analyse the clinical outcomes.Ethics and dissemination This study has received ethical approvals from the Human Research Ethics Committee at Charles Darwin University (H21089) and the Clinical Trial Ethics Committee at the Affiliated Hospital of Southwest Medical University (KY2022107). Findings from this study will be presented at academic conferences and submitted to peer-reviewed journals for publication.Trial registration number ClinicalTrials.gov: NCT05257876.

Abstract Background Studies in the West have demonstrated that appropriate informational support is a vital component of cancer care, with positive effects on both patients and their informal caregivers. Since little is known about the information needs of advanced cancer patients and informal caregivers in China, where ‘silence as virtue’ is much more valued and the communication style is less open, this study was therefore conducted to elaborate the information needs of advanced cancer patients and informal caregivers as well as to explore their perceptions and experiences regarding their unmet information needs in the Chinese context. Methods This sub-study of a previous cross-sectional survey utilized a qualitative descriptive study design. The approach involved semi-structured interviews that followed an interview guide to collect data. Eligible participants were the advanced cancer patients and informal caregivers who had participated in the previous cross-sectional survey and reported unmet information needs. Each interview was audio-recorded and transcribed verbatim. Descriptive content analysis was used to analyze the data. Results Seventeen advanced cancer patients and 15 informal caregivers with unmet information needs participated in the semi-structured interviews, with ages ranging from 32 to 63 years old for patients and from 32 to 70 for informal caregivers. Four categories were extracted from the interviews with the patients and caregivers: (1) types of unmet information needs; (2) reasons for information needs not being met; (3) preferences for the provision of information; and (4) meaning and role of information. Each category had two to four sub-categories for both the patients and the caregivers, which were similar but not completely the same. Conclusion The findings indicated that the provision of appropriate information could promote informed decision-making and greater satisfaction with treatment options, reductions in psychological disturbances, and enhanced confidence and ability in self-management and capacity in caregiving. Moreover, information on Traditional Chinese Medicine and food therapy should be increased, particularly for patients at the follow-up stage, while the amount of information on prognosis should be flexible as it could increase patients’ and caregivers’ psychological burden. Healthcare professionals were the most preferred information provider, although their heavy workload resulted in time constraints. In this case, they should provide information to patients and caregivers together as a ‘whole unit.’ At the same time, the value of separate conversations should also be recognized as some caregivers preferred to conceal unpleasant information from the patient.

Abstract Background High resolution 2D whole slide imaging provides rich information about the tissue structure. This information can be a lot richer if these 2D images can be stacked into a 3D tissue volume. A 3D analysis, however, requires accurate reconstruction of the tissue volume from the 2D image stack. This task is not trivial due to the distortions such as tissue tearing, folding and missing at each slide. Performing registration for the whole tissue slices may be adversely affected by distorted tissue regions. Consequently, regional registration is found to be more effective. In this paper, we propose a new approach to an accurate and robust registration of regions of interest for whole slide images. We introduce the idea of multi-scale attention for registration. Results Using mean similarity index as the metric, the proposed algorithm (mean ± SD $$0.84 \pm 0.11$$ 0.84 ± 0.11 ) followed by a fine registration algorithm ( $$0.86 \pm 0.08$$ 0.86 ± 0.08 ) outperformed the state-of-the-art linear whole tissue registration algorithm ( $$0.74 \pm 0.19$$ 0.74 ± 0.19 ) and the regional version of this algorithm ( $$0.81 \pm 0.15$$ 0.81 ± 0.15 ). The proposed algorithm also outperforms the state-of-the-art nonlinear registration algorithm (original: $$0.82 \pm 0.12$$ 0.82 ± 0.12 , regional: $$0.77 \pm 0.22$$ 0.77 ± 0.22 ) for whole slide images and a recently proposed patch-based registration algorithm (patch size 256: $$0.79 \pm 0.16$$ 0.79 ± 0.16 , patch size 512: $$0.77 \pm 0.16$$ 0.77 ± 0.16 ) for medical images. Conclusion Using multi-scale attention mechanism leads to a more robust and accurate solution to the problem of regional registration of whole slide images corrupted in some parts by major histological artifacts in the imaged tissue.

BackgroundA growing number of clinical practice guidelines (CPGs) regarding non-pharmacological interventions for breast cancer survivors are available. However, given the limitations in guideline development methodologies and inconsistent recommendations, it remains uncertain how best to design and implement non-pharmacological strategies to tailor interventions for breast cancer survivors with varied health conditions, healthcare needs, and preferences.AimTo critically appraise and summarise available non-pharmacological interventions for symptom management and health promotion that can be self-managed by breast cancer survivors based on the recommendations of the CPGs.MethodsCPGs, which were published between January 2016 and September 2021 and described non-pharmacological interventions for breast cancer survivors, were systematically searched in six electronic databases, nine relevant guideline databases, and five cancer care society websites. The quality of the included CPGs was assessed by four evaluators using The Appraisal of Guidelines for Research and Evaluation, second edition tool. Content analysis was conducted to synthesise the characteristics of the non-pharmacological interventions recommended by the included CPGs, such as the intervention’s form, duration and frequency, level of evidence, grade of recommendation, and source of evidence.ResultsA total of 14 CPGs were included. Among which, only five were appraised as high quality. The “range and purpose” domain had the highest standardized percentage (84.61%), while the domain of “applicability” had the lowest (51.04%). Five CPGs were rated “recommended”, seven were “recommended with modifications”, and the other two were rated “not recommended”. The content analysis findings summarised some commonly recommended self-managed non-pharmacological interventions in the 14 guidelines, including physical activity/exercise, meditation, hypnosis, yoga, music therapy, stress management, relaxation, massage and acupressure. Physical activity/exercise was the most frequently recommended approach to managing psychological and physical symptoms by the included guidelines. However, significant variations in the level of evidence and grade of recommendation were identified among the included CPGs.ConclusionRecommendations for the self-managed non-pharmacological interventions were varied and limited among the 14 CPGs, and some were based on medium- and low-quality evidence. More rigorous methods are required to develop high-quality CPGs to guide clinicians in offering high-quality and tailored breast cancer survivorship care.

PurposeThe vasodilatory response to inhaled CO2 occurs in the acute stroke ischemic penumbra and may be a potential therapeutic modality.MethodsTwenty-two Sprague-Dawley rats were subjected to 90-min occlusion of the M2 segment of the middle cerebral artery (M2CAO) by endovascular technique. The animals were administered different C02 concentrations and scanned serially with 9.4 T MRI. Infarct tissue was determined by diffusion-weighted imaging (DWI) and hypoperfused tissue was determined by arterial spin labeling (PWI).Results4 animals were administered room air (RA)+ 6% CO2 (group 1), 6 animals RA+12% CO2 (Group 2) and 4 animals only RA (group 3). In the rats with CO2 administered (groups 1 and 2), the DWI lesion to cerebral hypoperfusion volume ratio (SD) at pre-CO2 administration, was 0.145(0.168), which increased to 0.708(0.731) during CO2 administration and reduced to 0.533(0.527) post-CO2 administration. In 9 of 10 rats the hypoperfused volume decreased when CO2 was administered. When CO2 was stopped the hypoperfused volume became larger again. Administration of RA+12% CO2 (Group 2) decreased the volume of CBF hypoperfusion significantly compared to the control group (95%CI: 0.084 ± 0.0213, p = 0.004).ConclusionInhaled CO2 appears to reduce the size of the hypoperfused tissue volume during acute stroke and may be a potential modality for treatment of acute ischemic stroke. These findings will nonetheless need to be validated in a larger cohort in other centers.