Streptococcus Species Abundance in the Gut Is Linked to Subclinical Coronary Atherosclerosis in 8973 Participants From the SCAPIS Cohort.

BACKGROUND: Gut microbiota have been implicated in atherosclerotic disease, but their relation with subclinical coronary atherosclerosis is unclear. This study aimed to identify associations between the gut microbiome and computed tomography-based measures of coronary atherosclerosis and to explore relevant clinical correlates. METHODS: We conducted a cross-sectional study of 8973 participants (50 to 65 years of age) without overt atherosclerotic disease from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study). Coronary atherosclerosis was measured using coronary artery calcium score and coronary computed tomography angiography. Gut microbiota species abundance and functional potential were assessed with shotgun metagenomics sequencing of fecal samples, and associations with coronary atherosclerosis were evaluated with multivariable regression models adjusted for cardiovascular risk factors. Associated species were evaluated for association with inflammatory markers, metabolites, and corresponding species in saliva. RESULTS: The mean age of the study sample was 57.4 years, and 53.7% were female. Coronary artery calcification was detected in 40.3%, and 5.4% had at least 1 stenosis with >50% occlusion. Sixty-four species were associated with coronary artery calcium score independent of cardiovascular risk factors, with the strongest associations observed for Streptococcus anginosus and Streptococcus oralis subsp oralis (P<1×10-5). Associations were largely similar across coronary computed tomography angiography-based measurements. Out of the 64 species, 19 species, including streptococci and other species commonly found in the oral cavity, were associated with high-sensitivity C-reactive protein plasma concentrations, and 16 with neutrophil counts. Gut microbial species that are commonly found in the oral cavity were negatively associated with plasma indole propionate and positively associated with plasma secondary bile acids and imidazole propionate. Five species, including 3 streptococci, correlated with the same species in saliva and were associated with worse dental health in the Malmö Offspring Dental Study. Microbial functional potential of dissimilatory nitrate reduction, anaerobic fatty acid ß-oxidation, and amino acid degradation were associated with coronary artery calcium score. CONCLUSIONS: This study provides evidence of an association of a gut microbiota composition characterized by increased abundance of Streptococcus spp and other species commonly found in the oral cavity with coronary atherosclerosis and systemic inflammation markers. Further longitudinal and experimental studies are warranted to explore the potential implications of a bacterial component in atherogenesis.

Artificial intelligence-supported screen reading versus standard double reading in the Mammography Screening with Artificial Intelligence trial (MASAI): a clinical safety analysis of a randomised, controlled, non-inferiority, single-blinded, screening accuracy study.

BACKGROUND: Retrospective studies have shown promising results using artificial intelligence (AI) to improve mammography screening accuracy and reduce screen-reading workload; however, to our knowledge, a randomised trial has not yet been conducted. We aimed to assess the clinical safety of an AI-supported screen-reading protocol compared with standard screen reading by radiologists following mammography. METHODS: In this randomised, controlled, population-based trial, women aged 40-80 years eligible for mammography screening (including general screening with 1·5-2-year intervals and annual screening for those with moderate hereditary risk of breast cancer or a history of breast cancer) at four screening sites in Sweden were informed about the study as part of the screening invitation. Those who did not opt out were randomly allocated (1:1) to AI-supported screening (intervention group) or standard double reading without AI (control group). Screening examinations were automatically randomised by the Picture Archive and Communications System with a pseudo-random number generator after image acquisition. The participants and the radiographers acquiring the screening examinations, but not the radiologists reading the screening examinations, were masked to study group allocation. The AI system (Transpara version 1.7.0) provided an examination-based malignancy risk score on a 10-level scale that was used to triage screening examinations to single reading (score 1-9) or double reading (score 10), with AI risk scores (for all examinations) and computer-aided detection marks (for examinations with risk score 8-10) available to the radiologists doing the screen reading. Here we report the prespecified clinical safety analysis, to be done after 80 000 women were enrolled, to assess the secondary outcome measures of early screening performance (cancer detection rate, recall rate, false positive rate, positive predictive value [PPV] of recall, and type of cancer detected [invasive or in situ]) and screen-reading workload. Analyses were done in the modified intention-to-treat population (ie, all women randomly assigned to a group with one complete screening examination, excluding women recalled due to enlarged lymph nodes diagnosed with lymphoma). The lowest acceptable limit for safety in the intervention group was a cancer detection rate of more than 3 per 1000 participants screened. The trial is registered with ClinicalTrials.gov, NCT04838756, and is closed to accrual; follow-up is ongoing to assess the primary endpoint of the trial, interval cancer rate. FINDINGS: Between April 12, 2021, and July 28, 2022, 80 033 women were randomly assigned to AI-supported screening (n=40 003) or double reading without AI (n=40 030). 13 women were excluded from the analysis. The median age was 54·0 years (IQR 46·7-63·9). Race and ethnicity data were not collected. AI-supported screening among 39 996 participants resulted in 244 screen-detected cancers, 861 recalls, and a total of 46 345 screen readings. Standard screening among 40 024 participants resulted in 203 screen-detected cancers, 817 recalls, and a total of 83 231 screen readings. Cancer detection rates were 6·1 (95% CI 5·4-6·9) per 1000 screened participants in the intervention group, above the lowest acceptable limit for safety, and 5·1 (4·4-5·8) per 1000 in the control group-a ratio of 1·2 (95% CI 1·0-1·5; p=0·052). Recall rates were 2·2% (95% CI 2·0-2·3) in the intervention group and 2·0% (1·9-2·2) in the control group. The false positive rate was 1·5% (95% CI 1·4-1·7) in both groups. The PPV of recall was 28·3% (95% CI 25·3-31·5) in the intervention group and 24·8% (21·9-28·0) in the control group. In the intervention group, 184 (75%) of 244 cancers detected were invasive and 60 (25%) were in situ; in the control group, 165 (81%) of 203 cancers were invasive and 38 (19%) were in situ. The screen-reading workload was reduced by 44·3% using AI. INTERPRETATION: AI-supported mammography screening resulted in a similar cancer detection rate compared with standard double reading, with a substantially lower screen-reading workload, indicating that the use of AI in mammography screening is safe. The trial was thus not halted and the primary endpoint of interval cancer rate will be assessed in 100 000 enrolled participants after 2-years of follow up. FUNDING: Swedish Cancer Society, Confederation of Regional Cancer Centres, and the Swedish governmental funding for clinical research (ALF).

Serum immuno-oncology markers carry independent prognostic information in patients with newly diagnosed metastatic breast cancer, from a prospective observational study.

BACKGROUND: Metastatic breast cancer (MBC) is a challenging disease, and despite new therapies, prognosis is still poor for a majority of patients. There is a clinical need for improved prognostication where immuno-oncology markers can provide important information. The aim of this study was to evaluate serum immuno-oncology markers in MBC patients and their respective relevance for prediction of survival. PATIENTS AND METHODS: We investigated a broad panel of 92 immuno-oncology proteins in serum from 136 MBC patients included in a prospective observational study (NCT01322893) with long-term follow-up. Serum samples were collected before start of systemic therapy and analyzed using multiplex proximity extension assay (Olink Target 96 Immuno-Oncology panel). Multiple machine learning techniques were used to identify serum markers with highest importance for prediction of overall and progression-free survival (OS and PFS), and associations to survival were further evaluated using Cox regression analyses. False discovery rate was then used to adjust for multiple comparisons. RESULTS: Using random forest and random survival forest analyses, we identified the top nine and ten variables of highest predictive importance for OS and PFS, respectively. Cox regression analyses revealed significant associations (P < 0.005) of higher serum levels of IL-8, IL-10 and CAIX with worse OS in multivariable analyses, adjusted for established clinical prognostic factors including circulating tumor cells (CTCs). Similarly, high serum levels of IL-8, IL-10, ADA and CASP8 significantly associated with worse PFS. Interestingly, high serum levels of FasL significantly associated with improved OS and PFS. In addition, CSF-1, IL-6, MUC16, TFNSFR4 and CD244 showed suggestive evidence (P < 0.05) for an association to survival in multivariable analyses. After correction for multiple comparisons, IL-8 still showed strong evidence for correlation to survival. CONCLUSION: To conclude, we found six serum immuno-oncology markers that were significantly associated with OS and/or PFS in MBC patients, independently of other established prognostic factors including CTCs. Furthermore, an additional five serum immuno-oncology markers provided suggestive evidence for an independent association to survival. These findings highlight the relevance of immuno-oncology serum markers in MBC patients and support their usefulness for improved prognostication. Trial registration Clinical Trials (NCT01322893), registered March 25, 2011.

The role of primary care in the cancer care continuum: a qualitative study of cancer survivors' experiences.

OBJECTIVE: To explore how cancer survivors have experienced their contacts with primary care after being diagnosed with cancer, focusing on the integration between cancer specialist and primary care, and participants' views on what could make primary care services better at catering to the needs of cancer survivors. DESIGN: A qualitative study in which data was collected through semi-structured digital focus group interviews and analyzed using a template analysis approach. SETTING AND SUBJECTS: Adult residents of Skåne, Sweden, who had been diagnosed with and initiated treatment for either of five common cancer forms, recruited through patient advocacy groups. MAIN OUTCOME MEASURES: A qualitative description of participants' experiences and perceptions as expressed in focus group interview data. RESULTS: Most participants felt that primary care services had not played a significant role for them, despite patterns of both increased and unmet health needs. Insufficient coordination and communication with specialist cancer care, low availability, lacking personal continuity, low cancer competence and lacking commitment to cancer-related needs were presented as barriers to satisfactory primary care. A strengthened bond between cancer and primary care services, privileged access, and holistic perspectives were all suggested as measures to make primary care more suitable to cancer survivors' needs. CONCLUSION: The study suggests that cancer survivors experience a range of issues that hinders primary care services from playing a productive role in the cancer care process. The results speak for a need for interventions to remove barriers to satisfactory primary care contacts in this group of patients.KEY POINTSThe growing number of cancer survivors highlights the role of primary care services in the cancer care continuum.Despite the presence of unmet needs, few cancer survivors felt that primary care services had been significant to their care.Survivors identified a number of barriers to satisfactory primary care, including lacking coordination and communication between cancer and primary care.Strengthened links between healthcare services, privileged access, and holistic perspectives were suggested to improve primary care delivery for cancer survivors.

Laparoscopic distal pancreatectomy is more cost-effective than open resection: results from a Swedish randomized controlled trial.

BACKGROUND: Laparoscopic distal pancreatectomy is being implemented worldwide. The aim of this study was to perform a cost-effectiveness analysis from a health care perspective. METHODS: This cost-effectiveness analysis was based on the randomized controlled trial LAPOP, where 60 patients were randomized to open or laparoscopic distal pancreatectomy. For the follow-up of two years, resource use from a health care perspective was recorded, and health-related quality of life was assessed using the EQ-5D-5L. The per-patient mean cost and quality-adjusted life years (QALYs) were compared using nonparametric bootstrapping. RESULTS: Fifty-six patients were included in the analysis. The mean health care costs were lower, €3863 (95% CI: -€8020 to €385), for the laparoscopic group. Postoperative quality of life improved with laparoscopic resection and resulted in a gain in QALYs of 0.08 (95% CI: -0.09 to 0.25). The laparoscopic group had lower costs and improved QALYs in 79% of bootstrap samples. With a cost-per-QALY threshold of €50 000, 95.4% of the bootstrap samples were in favour of laparoscopic resection. CONCLUSION: Laparoscopic distal pancreatectomy is associated with numerically lower health care costs and improvements in QALYs compared with the open approach. The results support the ongoing transition from open to laparoscopic distal pancreatectomies.

Patient-reported participation in hepatopancreatobiliary surgery cancer care: A pilot intervention study with patient-owned fast-track protocols.

OBJECTIVE: Fast-track concepts have been implemented in hepatopancreatobiliary surgery cancer care to improve postoperative recovery. For optimal postoperative care, patient participation is also required. The aim was to investigate and analyse whether an intervention with patient-owned fast-track protocols (PFTPs) may lead to increased patient participation and improve information for patients who underwent surgery for hepatopancreatobiliary cancer. METHODS: A quantitative comparative design with a control and intervention group was used. The participants in the intervention group followed a PFTP during their admission. After discharge, the patients answered a questionnaire regarding patient participation. Data analyses were performed with descriptive statistics and ANCOVA. RESULTS: The results are based on a total of 222 completed questionnaires: 116 in the control group and 106 in the intervention group. It is uncertain whether the PFTP increased patient participation and information, but its use may indicate an improvement for the patient group. CONCLUSION: A successful implementation strategy for the use of PFTP, with daily reconciliations, could be part of the work required to improve overall satisfaction with patient participation. CLINICALTRIALS: gov ID: NCT04061902.

Plasticity in exocytosis revealed through the effects of repetitive stimuli affect the content of nanometer vesicles and the fraction of transmitter released.

Electrochemical techniques with disk and nano-tip electrodes, together with calcium imaging, were used to examine the effect of short-interval repetitive stimuli on both exocytosis and vesicular content in a model cell line. We show that the number of events decreases markedly with repeated stimuli suggesting a depletion of exocytosis machinery. However, repetitive stimuli induce a more stable fusion pore, leading to an increased amount of neurotransmitter release. In contrast, the total neurotransmitter content inside the vesicles decreases after repetitive stimuli, resulting in a higher average release fraction from each event. We suggest a possible mechanism regarding a link between activity-induced plasticity and fraction of release.

Facing an unexpected reality - oscillating between health and suffering 4-6 years after bariatric surgery.

BACKGROUND: Obesity is a significant public health problem that is on the increase worldwide, and treatment with bariatric surgery is becoming more and more common. This type of surgery has proved to be good for weight reduction and for preventing complications, but few studies have investigated patients' long-term experiences of health and suffering. AIM: To explore people's experiences of health after bariatric surgery. What are their thoughts about their life, body and sexuality? METHODS: This study is based on semi-structured interviews with eight women and eight men, 4-6 years after bariatric surgery. The data were analysed using qualitative content analysis and resulted in 5 main themes and 14 subthemes. RESULTS: The new body enabled a healthy life due to better treatment in society, enhanced self-esteem, the pleasure of purchasing clothes and the courage to become more sexually active. At the same time, the body could be experienced as so unfamiliar that their life was dominated by despondency, a lack of freedom and a feeling of being lost, which made them wish to return to their old body. CONCLUSION AND IMPLICATIONS: The participants received extensive information before as well as follow-up conversations up to one year after surgery. Nevertheless, they all experienced that changing from life as an obese person to a radically reduced body often meant a confrontation with an unexpected reality that oscillated between health and suffering. This indicates that preparedness for the life changes that bariatric surgery may entail is inadequate and that moving towards health and suffering takes its own time. Therefore, more time should be allocated to talking about how life is and can become in the long term, which may facilitate a dialogical, person-centred approach to the setbacks and situations each person needs to manage in order to improve her/his health.

Complications and chemotherapy have little impact on postoperative quality of life after pancreaticoduodenectomy - a cohort study.

BACKGROUND: With the poor prognosis of pancreatic cancer and the high rate of postoperative complications after pancreaticoduodenectomy, it is important to evaluate how the operation affects patients' quality of life. METHODS: This single-centre study included all patients undergoing pancreaticoduodenectomy from 2006 to 2016. Quality of life was measured with two questionnaires preoperatively, and at 6 and 12 months postoperatively. Comparisons between groups were made using a linear mixed models analysis. RESULTS: Of 279 patients planned for pancreaticoduodenectomy, 245 underwent the operation. The postoperative response rates were all 80% or more. Differences were found in one domain between the early and late time periods and three domains between patients receiving and not receiving adjuvant chemotherapy. No significant differences were found between patients with and without severe postoperative complications. However, the demographic variables of age group, sex, preoperative diabetes and smoking all exerted a significant impact on postoperative quality of life. CONCLUSION: While little or no impact was shown for the factors of postoperative complications, time period and adjuvant chemotherapy, demographic data, such as age, sex, preoperative diabetes and smoking, had considerable impacts on postoperative quality of life after pancreaticoduodenectomy.

Simultaneous or staged resection of synchronous colorectal cancer liver metastases: a 13-year institutional follow-up.

BACKGROUND: This study compared postoperative outcomes and survival rates of patients who underwent simultaneous or staged resection for synchronous colorectal cancer liver metastases. METHODS: Between 2005 and 2018, 126 patients were registered prospectively at a university hospital in Sweden, 63 patients who underwent simultaneous resection were matched against 63 patients who underwent staged resection. RESULTS: The length of hospital stay was shorter for the simultaneous resection group, at 11 vs 16 days, p = <0.001. Fewer patients experienced recurrence in the simultaneous resection group 39 vs 50 patients, p = 0.012. There were no significant differences in disease-free survival and overall survival between the groups. Age (hazard ratio [HR] 1.72; 95% CI 1.01-2.94; p = 0.049) and Clavien-Dindo score (HR 2.22; 95% CI 1.06-4.67; p = 0.035) had impact on survival. CONCLUSION: Colorectal cancer with synchronous liver metastases can be resected simultaneously, and enables a shorter treatment time without jeopardizing oncological outcomes.

Patient preferences and experiences of participation in surgical cancer care.

BACKGROUND: Quality cancer care necessitates opportunities for patient participation, supposedly recognizing the individual's preferences and experiences for being involved in their health and healthcare issues. Previous research shows that surgical cancer patients wish to be more involved, requiring professionals to be sensitive of patients' needs. AIMS: To explore preference-based patient participation in surgical cancer care. METHODS: A cross-sectional study was conducted. The Patient Preferences for Patient Participation tool (4Ps) was used, which includes 12 attributes of preferences for and experiences of patient participation. Data were analyzed with descriptive and comparative statistical methods. RESULTS: The results are based on a total of 101 questionnaires. Having reciprocal communication and being listened to by healthcare staff were commonly deemed crucial for patient participation. While 60% of the patients suggested that taking part in planning was crucial for their participation, they had experienced this only to some extent. Learning to manage symptoms and phrasing personal goals were items most often representing insufficient conditions for preference-based patient participation. LINKING EVIDENCE TO ACTION: To support person-centered surgical care, further efforts to suffice preference-based participation are needed, including opportunities for patients to share their experiences and engage in the planning of healthcare activities.

ALPPS Improves Survival Compared With TSH in Patients Affected of CRLM: Survival Analysis From the Randomized Controlled Trial LIGRO.

OBJECTIVE: To evaluate the oncological outcome for patients with colorectal liver metastases (CRLM) randomized to associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) or 2-stage hepatectomy (TSH). BACKGROUND: TSH with portal vein occlusion is an established method for patients with CRLM and a low volume of the future liver remnant (FLR). ALPPS is a less established method. The oncological outcome of these methods has not been previously compared in a randomized controlled trial. METHODS: One hundred patients with CRLM and standardized FLR (sFLR) <30% were included and randomized to resection by ALPPS or TSH, with the option of rescue ALPPS in the TSH group, if the criteria for volume increase was not met. The first radiological follow-up was performed approximately 4 weeks postoperatively and then after 4, 8, 12, 18, and 24 months. At all the follow-ups, the remaining/recurrent tumor was noted. After the first follow-up, chemotherapy was administered, if indicated. RESULTS: The resection rate, according to the intention-to-treat principle, was 92% (44 patients) for patients randomized to ALPPS compared with 80% (39 patients) for patients randomized to TSH (P = 0.091), including rescue ALPPS. At the first postoperative follow-up, 37 patients randomized to ALPPS were assessed as tumor free in the liver, and also 28 patients randomized to TSH (P = 0.028). The estimated median survival for patients randomized to ALPPS was 46 months compared with 26 months for patients randomized to TSH (P = 0.028). CONCLUSIONS: ALPPS seems to improve survival in patients with CRLM and sFLR <30% compared with TSH.

The advanced machine learner XGBoost did not reduce prehospital trauma mistriage compared with logistic regression: a simulation study.

BACKGROUND: Accurate prehospital trauma triage is crucial for identifying critically injured patients and determining the level of care. In the prehospital setting, time and data are often scarce, limiting the complexity of triage models. The aim of this study was to assess whether, compared with logistic regression, the advanced machine learner XGBoost (eXtreme Gradient Boosting) is associated with reduced prehospital trauma mistriage. METHODS: We conducted a simulation study based on data from the US National Trauma Data Bank (NTDB) and the Swedish Trauma Registry (SweTrau). We used categorized systolic blood pressure, respiratory rate, Glasgow Coma Scale and age as our predictors. The outcome was the difference in under- and overtriage rates between the models for different training dataset sizes. RESULTS: We used data from 813,567 patients in the NTDB and 30,577 patients in SweTrau. In SweTrau, the smallest training set of 10 events per free parameter was sufficient for model development. XGBoost achieved undertriage rates in the range of 0.314-0.324 with corresponding overtriage rates of 0.319-0.322. Logistic regression achieved undertriage rates ranging from 0.312 to 0.321 with associated overtriage rates ranging from 0.321 to 0.323. In NTDB, XGBoost required the largest training set size of 1000 events per free parameter to achieve robust results, whereas logistic regression achieved stable performance from a training set size of 25 events per free parameter. For the training set size of 1000 events per free parameter, XGBoost obtained an undertriage rate of 0.406 with an overtriage of 0.463. For logistic regression, the corresponding undertriage was 0.395 with an overtriage of 0.468. CONCLUSION: The under- and overtriage rates associated with the advanced machine learner XGBoost were similar to the rates associated with logistic regression regardless of sample size, but XGBoost required larger training sets to obtain robust results. We do not recommend using XGBoost over logistic regression in this context when predictors are few and categorical.

Patient involvement in surgical care-Healthcare personnel views and behaviour regarding patient involvement.

BACKGROUND: All professions in surgical care have a responsibility to include patients in their health care. By Swedish law, all care should be done in dialogue with the patient. The essential part of health care is the meeting between patient and healthcare professional. In the interaction, a decision can be made, and needs can be identified to a safer care. Previous studies on patient participation have focussed on patients' perspectives in surgical care, but there is a paucity of studies about the personnel's perspective of estimated patient involvement in surgical care. AIM: The aim of this study was to identify and describe healthcare personnel's view and behaviour regarding patient involvement in surgical care. METHOD: A quantitative study with various professions was conducted. A validated questionnaire was used, remaining questions grouped under following areas: patient involvement, acute phase, hospital time, discharge phase and questions on employment and workplace. RESULTS: A total of 140 questionnaires were sent out to a surgical clinic in Sweden, and 102 questionnaires were answered. All professionals stated that clear information is an important part of patient involvement in surgical care. Statistically significant differences existed between the professions in the subscale information. Physicians rated their information higher than the Registered Nurses (p = 0.005) and the practical nurses did (p = 0.001). Hindrances to involving patients were lack of time and other priority tasks. CONCLUSIONS: Professionals in surgical care graded information to be the most important thing for patient involvement. Participation in important decisions, including the possibility to express personal views and ask questions, is important factors for patient involvement. Barriers against patient involvement are lack of time and prioritisation of other work activities.

Clinical relevance of systemic monocytic-MDSCs in patients with metastatic breast cancer.

The overall aim of this prospective study was to delineate the role of monocytic myeloid-derived suppressor cells (Mo-MDSCs) in patients with metastatic breast cancer (MBC). MDSCs are a heterogeneous group of immunosuppressive cells often enriched in different malignancies which hold prognostic and predictive value for clinical outcomes. Here, we assessed the clinical significance of Mo-MDSCs in 54 patients with de novo or distant recurrent MBC. We show that high levels of Mo-MDSCs significantly correlated with de novo MBC (metastatic disease at initial diagnosis), estrogen receptor (ER) negativity, and liver- and bone metastasis. A trend towards an association between high levels of Mo-MDSCs and survival (P = 0.053) was also found in patients with distant recurrent ER-positive MBC. We therefore propose that an increased population of Mo-MDSCs may be related to the metastatic or immunoregulatory switch associated with transition to a more systemic disease. Our data imply that high levels of systemic Mo-MDSCs represent patients with more aggressive disease and worse outcome.

Evolution of Estrogen Receptor Status from Primary Tumors to Metastasis and Serially Collected Circulating Tumor Cells.

BACKGROUND: The estrogen receptor (ER) can change expression between primary tumor (PT) and distant metastasis (DM) in breast cancer. A tissue biopsy reflects a momentary state at one location, whereas circulating tumor cells (CTCs) reflect real-time tumor progression. We evaluated ER-status during tumor progression from PT to DM and CTCs, and related the ER-status of CTCs to prognosis. METHODS: In a study of metastatic breast cancer, blood was collected at different timepoints. After CellSearch® enrichment, CTCs were captured on DropMount slides and evaluated for ER expression at baseline (BL) and after 1 and 3 months of therapy. Comparison of the ER-status of PT, DM, and CTCs at different timepoints was performed using the McNemar test. The primary endpoint was progression-free survival (PFS). RESULTS: Evidence of a shift from ER positivity to negativity between PT and DM was demonstrated (p = 0.019). We found strong evidence of similar shifts from PT to CTCs at different timepoints (p < 0.0001). ER-positive CTCs at 1 and 3 months were related to better prognosis. CONCLUSIONS: A shift in ER-status from PT to DM/CTCs was demonstrated. ER-positive CTCs during systemic therapy might reflect the retention of a favorable phenotype that still responds to therapy.

Intracellular Electrochemical Nanomeasurements Reveal that Exocytosis of Molecules at Living Neurons is Subquantal and Complex.

Since the early work of Bernard Katz, the process of cellular chemical communication through exocytosis, quantal release, has been considered to be all or none. Recent evidence has shown exocytosis to be partial or "subquantal" at single-cell model systems, but there is a need to understand this at communicating nerve cells. Partial release allows nerve cells to control the signal at the site of release during individual events, for which the smaller the fraction released, the greater the range of regulation. Herein, we show that the fraction of the vesicular octopamine content released from a living Drosophila larval neuromuscular neuron is very small. The percentage of released molecules was found to be only 4.5 % for simple events and 10.7 % for complex (i.e., oscillating or flickering) events. This large content, combined with partial release controlled by fluctuations of the fusion pore, offers presynaptic plasticity that can be widely regulated.

'I want to know why and need to be involved in my own care ': a qualitative interview study with liver, bile duct or pancreatic cancer patients about their experiences with involvement in care.

PURPOSE: Patients' involvement in their own care is important for those with upper abdominal tumours. Care is often conducted according to standardized fast-track care programs (FTCP), and a shorter hospital stay is one of the goals. However, there is no research providing an in-depth perspective on patients' experiences of involvement in care. In this qualitative study, we explored experiences of involvement among patients who had surgery for upper abdominal tumours and were cared for according to an FTCP. METHODS: Qualitative in-depth face-to-face interviews about patient involvement in care were conducted with 20 patients who had surgery for the liver, bile duct, or pancreatic cancer using an open-interview guide. RESULTS: The most important findings are that customized information and active dialogue about care decisions stimulate patient involvement. We identified three themes from the analysed data: involvement depended on the quality of information, communication and involvement during the care period, and safety at discharge. CONCLUSIONS: Individualized care and continuous information about treatment and care goals in the FTCP during the care process create trust between patients and healthcare professionals and increase patient experiences of involvement.

Information is the key to successful participation for patients receiving surgery for upper gastrointestinal cancer.

Fast-track programmes are aimed at improving perioperative care. The purpose of this study was to identify and explore patient participation among patients who had surgery for liver, bile duct or pancreatic cancer and followed a fast-track programme. A total of 116 questionnaires to investigate patient participation were analysed. Information was important for the patients, as was having the opportunity to ask questions and express personal views. The results showed differences by sex; men responded to a greater extent that they did not want to make decisions as a patient (p = 0.044) and that they had been motivated to take more responsibility for their future health (p = 0.011). Patients with pancreatic cancer discussed treatment goals with doctors to a greater extent than did patients with liver cancer (p = 0.041). Half of the patients perceived that they had not been involved in their care planning after discharge but had a desired to be involved. This seems to be an important point to improve in future care, and also that professionals should be aware of patients' needs for information and participation, especially at discharge.

Burnout among school teachers: quantitative and qualitative results from a follow-up study in southern Sweden.

BACKGROUND: Teachers are at high risk of stress-related disorders. This longitudinal study aimed to (a) identify which occupational, sociodemographic and life-style factors and self-efficacy at baseline that were of importance for burnout, (b) explore associations between changes in the studied factors versus changes in burnout, and (c) by interviews increase the understanding of perceived job demands among teachers. METHODS: A cohort of 310 Swedish teachers in school-years 4-9 responded to a questionnaire of occupational, sociodemographic and life-style factors, self-efficacy and burnout, at baseline and at follow-up (mean 30 months later). A combined measure with four levels of burnout was crafted, based on exhaustion, cynicism and professional efficacy (Maslach Burnout Inventory-General Survey). Quantitative data were analysed with multiple ordinal regression, and qualitative data were analysed with content analysis of interview responses from a subgroup of the teachers (n = 81). RESULTS: The occurrence of high burnout (level 2 and 3 combined) were similar at baseline and follow-up (14% vs. 15%). However, many teachers fluctuated between the levels of burnout (28% increased and 24% decreased). Burnout at baseline was of importance for change of work or being off duty at follow up. In the multi-exposure model, low self-efficacy [OR 0.42; CI 0.26-0.68] and high job demands [OR 1.97; CI 1.02-3.8] were the strongest explanatory variables. Low self-efficacy remained as the strongest explanatory factor after adjustment for burnout at baseline. Increased job demands during follow-up was associated with an increased level of burnout [OR 3.41; CI 1.73-6.69], whereas increased decision latitude was associated with a decreased level of burnout [OR 0.51; CI 0.30-0.87]. Two major categories of demands emerged in the qualitative analysis; i.e. too high workload and a sense of inadequacy. CONCLUSIONS: A substantial proportion of teachers showed signs of burnout at both occasions. Low self-efficacy and high job demands was of importance for burnout, and changes in burnout was further associated with changes in decision latitude. The results points to the need of actions on individual, organizational and a societal levels.