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Abstract Background Multiple myeloma (MM) is at present an incurable malignancy, characterized by apoptosis-resistant tumor cells. Interferon (IFN) treatment sensitizes MM cells to Fas-induced apoptosis and is associated with an increased activation of Signal transducer and activator of transcription (Stat)1. The role of Stat1 in MM has not been elucidated, but Stat1 has in several studies been ascribed a pro-apoptotic role. Conversely, IL-6 induction of Stat3 is known to confer resistance to apoptosis in MM. Methods To delineate the role of Stat1 in IFN mediated sensitization to apoptosis, sub-lines of the U-266-1970 MM cell line with a stable expression of the active mutant Stat1C were utilized. The influence of Stat1C constitutive transcriptional activation on endogenous Stat3 expression and activation, and the expression of apoptosis-related genes were analyzed. To determine whether Stat1 alone would be an important determinant in sensitizing MM cells to apoptosis, the U-266-1970-Stat1C cell line and control cells were exposed to high throughput compound screening (HTS). Results To explore the role of Stat1 in IFN mediated apoptosis sensitization of MM, we established sublines of the MM cell line U-266-1970 constitutively expressing the active mutant Stat1C. We found that constitutive nuclear localization and transcriptional activity of Stat1 was associated with an attenuation of IL-6-induced Stat3 activation and up-regulation of mRNA for the pro-apoptotic Bcl-2 protein family genes Harakiri, the short form of Mcl-1 and Noxa. However, Stat1 activation alone was not sufficient to sensitize cells to Fas-induced apoptosis. In a screening of > 3000 compounds including bortezomib, dexamethasone, etoposide, suberoylanilide hydroxamic acid (SAHA), geldanamycin (17-AAG), doxorubicin and thalidomide, we found that the drug response and IC50 in cells constitutively expressing active Stat1 was mainly unaltered. Conclusion We conclude that Stat1 alters IL-6 induced Stat3 activity and the expression of pro-apoptotic genes. However, this shift alone is not sufficient to alter apoptosis sensitivity in MM cells, suggesting that Stat1 independent pathways are operative in IFN mediated apoptosis sensitization.

Background: Older adults have complex medical needs that causes increased use of resources at the emergency department (ED). The prevalence of non-specific complaint (NSC) as a chief-complaint in the ED is common among older adults and is not prioritized even though possibly having worse clinical outcome. The objective was to study hospital admission and mortality for older adults visiting the ED with NSC compared to specific complaints such as dyspnea, chest pain and abdominal pain., Methods: A retrospective observational study of older adults visiting the ED with NSC and specific complaints; dyspnea, chest pain and abdominal pain was performed. Chief-complaint were collected from electronic medical records. Fatigue, confusion, non-specific complaints, generalized weakness and risk of falling were defined as non-specific complaint (NSC) when registered as chief-complaint at the ED. Admission rate and 30-days mortality were the primary outcomes., Results: A total of 4927 patients were included in the study based on chief-complaint; patients with chest pain 1599 (32%), dyspnea 1343 (27%), abdominal pain 1460 (30%) and NSC 525 (11%). Patients with dyspnea and NSC had the highest hospital admission rate 79% vs 70% compared to patients with chest pain (63%) and abdominal pain (61%) (p =  < 0.001). Patients with NSC had a mean LOS 4.7 h at the ED which was significantly higher compared to chest pain, dyspnea and abdominal pain. Mean bed-days for the whole population was 4.2 days compared to patients with NSC who had a mean LOS of 5.6 days. NSC and dyspnea were both associated with the highest 30-day mortality., Conclusion: Older patients who present with NSC at the ED are associated with a high risk for admission and 30-days mortality. In addition, patients with NSC have a longer LOS at the ED, a high admission rate and the highest number of bed-days once admitted. This study indicates that ED staff should be more vigilant when an elderly patient presents with NSC at the ED. Further studies and guidelines are needed to improve the management of these individuals., (© 2023. The Author(s).)

Background: Patients on home hemodialysis (HHD) exhibit superior survival compared with patients on institutional hemodialysis (IHD) and peritoneal dialysis (PD). There is a sparsity of reports comparing morbidity between HHD and IHD or PD and none in a European population. The aim of this study is to compare morbidity between modalities in a Swedish population., Methods: The Swedish Renal Registry was used to retrieve patients starting on HHD, IHD or PD. Patients were matched according to sex, age, comorbidity and start date. The Swedish Inpatient Registry was used to determine comorbidity before starting renal replacement therapy (RRT) and hospital admissions during RRT. Dialysis technique survival was compared between HHD and PD., Results: RRT was initiated with HHD for 152 patients; these were matched with 608 patients with IHD and 456 with PD. Patients with HHD had significantly lower annual admission rate and number of days in hospital. (median 1.7 admissions; 12 days) compared with IHD (2.2; 14) and PD (2.8; 20). The annual admission rate was significantly lower for patients with HHD compared with IHD for cardiovascular diagnoses and compared with PD for infectious disease diagnoses. Dialysis technique survival was significantly longer with HHD compared with PD., Conclusions: Patients choosing HHD as initial RRT spend less time in hospital compared with patients on IHD and PD and they were more likely than PD patients, to remain on their initial modality. These advantages, in combination with better survival and higher likelihood of renal transplantation, are important incentives for promoting the use of HHD.

For a long time the attention given to the hip fracture patient group was minor and without any certain consideration to their frailty. To improve the care for these patients Skane University Hospital in Lund has during the past 19 years worked actively with developing the care. This paper aims to describe what impact the care process development has had on functional outcome and mortality, as well as to analyze the impact of comorbidity and fracture type., Methods: Patients older than 50 years with non-pathological cervical and trochanteric hip fracture admitted between Jan 1st 1999 and Dec 31st 2017 were included and data was retrieved from the National Quality Register for hip fracture patients, RIKSHÖFT. Variables regarding patient characteristics, fracture type, operation method, lead-times and outcome were analyzed. For comparison Fischer's exact test and Spearman's rank correlation coefficient was used for the categorical data and Pearson correlation coefficient for the continuous. To further analyze the effect over time a linear regression model was used., Results: A total of 7827 patients were included. A significant shift in the overall morbidity was seen, with an increase in patients of higher ASA grade. No correlation was seen between outcome and the care process development. The mortality rate for the group as a whole the mortality rate had decreased over time. The total length of stay had decreased significantly over time. There was no statistically significant change in mortality rate over time when relating it to time-to-surgery., Conclusions: Although the patients display a higher morbidity over time, the mortality rate has not changed significantly, which might indicate an effect of the care process development. The care process development does not seem to impact on outcome as much as other factors. This study supports the possibility to create a more specific algorithm for hip fracture patients, taking specific subgroups into consideration.

Background: The survival rate for dialysis patients is poor. Previous studies have shown improved survival with home hemodialysis (HHD), but this could be due to patient selection, since HHD patients tend to be younger and healthier. The aim of the present study is to analyse the long-term effects of HHD on patient survival and on subsequent renal transplantation, compared with institutional hemodialysis (IHD) and peritoneal dialysis (PD), taking age and comorbidity into account., Methods: Patients starting HHD as initial renal replacement therapy (RRT) were matched with patients on IHD or PD, according to gender, age, Charlson Comorbidity Index and start date of RRT, using the Swedish Renal Registry from 1991 to 2012. Survival analyses were performed as intention-to-treat (disregarding changes in RRT) and per-protocol (as on initial RRT)., Results: A total of 152 patients with HHD as initial RRT were matched with 608 IHD and 456 PD patients, respectively. Median survival was longer for HHD in intention-to-treat analyses: 18.5 years compared with 11.9 for IHD (p <  0.001) and 15.0 for PD (p = 0.002). The difference remained significant in per-protocol analyses omitting the contribution of subsequent transplantation. Patients on HHD were more likely to receive a renal transplant compared with IHD and PD, although treatment modality did not affect subsequent graft survival (p > 0.05)., Conclusion: HHD as initial RRT showed improved long-term patient survival compared with IHD and PD. This survival advantage persisted after matching and adjusting for a higher transplantation rate. Dialysis modality had no impact on subsequent graft survival.

Background: Emergency department (ED) overcrowding is frequently described in terms of input- throughput and output. In order to reduce ED input, a concept called primary triage has been introduced in several Swedish EDs. In short, primary triage means that a nurse separately evaluates patients who present in the Emergency Department (ED) and either refers them to primary care or discharges them home, if their complaints are perceived as being of low acuity. The aim of the present study is to elucidate whether high levels of in-hospital bed occupancy are associated with decreased permeability in primary triage. The appropriateness of discharges from primary triage is assessed by 72-h revisits to the ED., Methods: The study is a retrospective cohort study on administrative data from the ED at a 420-bed hospital in southern Sweden from 2011-2012. In addition to crude comparisons of proportions experiencing each outcome across strata of in-hospital bed occupancy, multivariate models are constructed in order to adjust for age, sex and other factors., Results: A total of 37,129 visits to primary triage were included in the study. 53.4 % of these were admitted to the ED. Among the cases referred to another level of care, 8.8 % made an unplanned revisit to the ED within 72 h. The permeability of primary triage was not decreased at higher levels of in-hospital bed occupancy. Rather, the permeability was slightly higher at occupancy of 100-105 % compared to <95 % (OR 1.09 95 % CI 1.02-1.16). No significant association between in-hospital bed occupancy and the probability of 72-h revisits was observed., Conclusions: The absence of a decreased permeability of primary triage at times of high in-hospital bed occupancy is reassuring, as the opposite would have implied that patients might be denied entry not only to the hospital, but also to the ED, when in-hospital beds are scarce.

Ageing populations and higher ambitions continuously drive healthcare costs in Sweden and worldwide. During the last two decades, downsizing hospital bed capacity has been the strategy for cutting expenditure in the Swedish healthcare system. However, the lack of implementation of new and viable outpatient alternatives has led to a widespread overcrowding problem in Swedish hospitals and emergency departments. The present study was conducted as a survey in hospital wards at two emergency hospitals in southwestern Sweden. Study aims were to assess the causes of hospitalization and indications for continuing in-hospital care in hospitalized geriatric patients (>80 years). The study shows that a very small number of patients are admitted barely because of social factors; however, there is a significant group where hospitalization is due to both social and medical factors. A large group of hospitalized patients over 80 year (37%) could receive their care outside the emergency hospital. About 30% of hospitalized patients are waiting for planning, and the majority of them waiting for social action and planning. Older patients with multiple diseases require healthcare but not hospitalization to the present extent. We should focus on developing additional forms of healthcare since avoidable hospitalization is a high cost for the society, but above all a risk for the individual.

Background: Previous work has suggested that given a hospital's need to admit more patients from the emergency department (ED), high inpatient bed occupancy may encourage premature hospital discharges that favor the hospital's need for beds over patients' medical interests. We argue that the effects of such action would be measurable as a greater proportion of unplanned hospital readmissions among patients discharged when the hospital was full than when not. In response, the present study tested this hypothesis by investigating the association between inpatient bed occupancy at the time of hospital discharge and the 30-day readmission rate., Methods: The sample included all inpatient admissions from the ED at a 420-bed emergency hospital in southern Sweden during 2011-2012 that resulted in discharge before 1 December 2012. The share of unplanned readmissions within 30 days was computed for levels of inpatient bed occupancy of <95%, 95-100%, 100-105% and >105% at the hour of discharge. A binary logistic regression model was constructed to adjust for age, time of discharge, and other factors that could affect the outcome., Results: In all, 32,811 visits were included in the study, 9.9% of which resulted in an unplanned readmission within 30 days of discharge. The proportion of readmissions was 9.0% for occupancy levels of <95% at the patient's discharge, 10.2% for 95-100% occupancy, 10.8% for 100-105% occupancy, and 10.5% for >105% occupancy (p = 0.0001). Results from the multivariate models show that the OR (95% CI) of readmission was 1.11 (1.01-1.22) for patients discharged at 95-100% occupancy, 1.17 (1.06-1.29) at 100-105% occupancy, and 1.15 (0.99-1.34) at >105% occupancy., Conclusions: Results indicate that patients discharged from inpatient wards at times of high inpatient bed occupancy experience an increased risk of unplanned readmission within 30 days of discharge.

Background: A possible downstream effect of high in-hospital bed occupancy is that patients in the emergency department (ED) who would benefit from in-hospital care are denied admission. The present study aimed at evaluating this hypothesis through investigating associations between in-hospital bed occupancy at the time of presentation in the ED and the probability for unplanned 72-hour (72-h) revisits to the ED among patients discharged at index. A second outcome was unplanned 72-h revisits resulting in admission., Methods: All visits to the ED of a 420-bed emergency hospital in southern Sweden between 1 January 2011 and 31 December 2012, which did not result in admission, death, or transfer to another hospital were included. Revisiting fractions were computed for in-hospital occupancy intervals <85%, 85% to 90%, 90% to 95%, 95% to 100%, 100% to 105%, and ≥105%. Multivariate models were constructed in an attempt to take confounding factors from, e.g., presenting complaints, age, referral status, and triage priority into account., Results: Included in the study are 81,878 visits. The fraction of unplanned 72-h revisits/unplanned 72-h revisits resulting in admission was 5.8%/1.4% overall, 6.2%/1.4% for occupancy <85%, 6.4%/1.5% for occupancy 85% to 90%, 5.8%/1.4% for occupancy 90% to 95%, 6.0%/1.6% for occupancy 95% to 100%, 5.4%/1.6% for occupancy 100% to 105%, and 4.9%/1.4% for occupancy ≥105%. In the multivariate models, a trend to lower probability of unplanned 72-h revisits was observed at occupancy ≥105% compared to occupancy <95% (OR 0.88, CI 0.76 to 1.01). No significant associations between in-hospital occupancy at index and the probability of making unplanned 72-h revisits resulting in admission were observed., Conclusions: The lack of associations between in-hospital occupancy and unplanned 72-h revisits does not support the hypothesis that ED patients are inappropriately discharged when in-hospital beds are scarce. The results are reassuring as they indicate that physicians are able to make good decisions, also while resources are constrained.

Background: In 2005, the Advanced Life Support (ALS) teams delivering pre-hospital care in RegionSkane in southern Sweden received additional support by physicians, who were part of "Pre-hospital acute teams" (PHAT). The study objective is to compare the incidence of pre-hospital medical interventions for trauma-patients cared for by conventional ALS teams and patients who received additional support by PHAT., Methods: Trauma patients with Injury Severity Score (ISS) >9 were identified retrospectively in the national quality registry KVITTRA at three hospitals in RegionSkane, for the time period October 2005 to December 2008. Interventions include e.g. tracheal intubation, administration of i.v. fluids, neck immobilization and spine board usage. Confounding effects from trauma severity, trauma mechanism, vital parameters, age and sex were addressed in multivariate models., Results: Data from 202 cases was included. 9 pre-hospital interventions were assessed. The incidence of endotracheal intubation and immobilisation of extremities was higher among patients in the PHAT-group compared to the ALS-only group (16.3% vs. 6.9%, p = 0.034) and (12.8% vs. 4.3%, p = 0.027) respectively. PHATs presence remained a significant predictor of these interventions also after taking confounding factors into account (OR 5.5, CL 1.5-19.7) and (OR 3.2 CI 1.0-9.8).PHAT was involved in a greater proportion of cases with <50.0% of survival (19.8% vs. 12.1%, p = 0.134). The average ISS was higher among cases receiving PHAT support in strata ISS 16-24 and ISS > 24 than cases in corresponding strata cared for by ALS teams alone (ISS 20.0 vs. 17.0, p = 0.048 and ISS 34.0 vs. 29.0, p = 0.019)., Conclusions: The incidence of endotracheal intubation and immobilization of extremities was greater among patients supported by PHAT, compared to patients cared for by ALS teams alone. This finding has to be interpreted in the light of a selection-bias where PHAT support was directed to more severely injured patients.

Background: The association between emergency department (ED) overcrowding and poor patient outcomes is well described, with recent work suggesting that the phenomenon causes delays in time-sensitive interventions, such as resuscitation. Even though most researchers agree on the fact that admitted patients boarding in the ED is a major contributing factor to ED overcrowding, little work explicitly addresses whether in-hospital occupancy is associated to the probability of patients being admitted from the ED. The objective of the present study is to investigate whether such an association exists., Methods: Retrospective analysis of data on all ED visits to Helsingborg General Hospital in southern Sweden between January 1, 2011, and December 31, 2012, was undertaken. The fraction of admitted patients was calculated separately for strata of in-hospital occupancy <95%, 95-100%, 100-105%, and >105%. Multivariate models were constructed in an attempt to take confounding factors, e.g., presenting complaints, age, referral status, triage priority, and sex into account. Subgroup analysis was performed for each specialty unit within the ED., Results: Overall, 118,668 visits were included. The total admitted fraction was 30.9%. For levels of in-hospital occupancy <95%, 95-100%, 100-105%, and >105% the admitted fractions were 31.5%, 30.9%, 29.9%, and 28.7%, respectively. After taking confounding factors into account, the odds ratio for admission were 0.88 (CI 0.84-0.93, P >0.001) for occupancy level 95-100%, 0.82 (CI 0.78-0.87, P >0.001) for occupancy level 100-105%, and 0.74 (CI 0.67-0.81, P >0.001) for occupancy level >105%, relative to the odds ratio for admission at occupancy level <95%. A similar pattern was observed upon subgroup analysis., Conclusions: In-hospital occupancy was significantly associated with a decreased odds ratio for admission in the study population. One interpretation is that patients who would benefit from inpatient care instead received suboptimal care in outpatient settings at times of high in-hospital occupancy. A second interpretation is that physicians admit patients who could be managed safely in the outpatient setting, in times of good in-hospital bed availability. Physicians thereby expose patients to healthcare-associated infections and other hazards, in addition to consuming resources better needed by others.

Background: Local tumour destruction has been shown to give rise to changes in immunocompetent cells. The aim of this study was to describe the effect of interstitial laser thermotherapy (ILT) of breast carcinoma in the tumour and in regional lymph nodes., Methods: Seventeen women that underwent radical surgical excision after non-radical ILT were studied. ILT was performed at a steady-state temperature of 48°C for 30 min. Surgical excision was performed 12 (6-23) days after ILT. Six patients with breast cancer not treated with ILT before surgery served as controls. Immunohistological reactions were performed on core needle biopsies prior to treatment and on the excised specimens., Results: ILT resulted in more CD8 lymphocytes and CD68 macrophages within the tumour (P < 0.05 and P < 0.01, respectively) and higher counts of CD20 (P < 0.05), CD68 (P < 0.001) and CD83 (P < 0.01) at the tumour border, when compared to pre-treatment values. In the control patients not receiving ILT, CD8 cells increased within the tumour after resection (P < 0.05). With the probable exception of CD25 Foxp3 cells, the presence of cancer in a lymph node influenced the findings in lymph nodes (examined for CD1a, CD25, Foxp3 CD25, CD83 cells). Thus, comparisons between ILT and control patients were restricted to patients without lymph node metastases. In these patients, ILT and resection were followed by a decrease in CD25 Foxp3 lymphocytes (P < 0.05), when compared to surgical resection alone., Conclusions: ILT induced changes in immunocompetent cells in patients with breast cancer. The stimulation of the immune system is an added feature of ILT in treatment of patients with breast cancer.

Multiple myeloma (MM) is an as-yet incurable B-cell malignancy. Increased survival in vitro is a hallmark of MM cells, implying that a therapeutic potential may lie in circumventing antiapoptotic signals. We have previously reported that interferons (IFNs) sensitize MM cells to Fas/CD95-mediated apoptosis. In the present study, we explore the mechanism underlying this effect. In a wide screening of apoptosis-related genes, Apo2L/TRAIL (tumor necrosis factor [TNF]-related apoptosis inducing ligand) and Fas were identified as IFN targets. Sensitization to Fas-mediated apoptosis by IFNs was not affected by blocking Apo2L/TRAIL, suggesting that Apo2L/TRAIL is not a key mediator in this process. In contrast, we found that an elevated Fas expression was functionally linked to increased susceptibility to Fas-mediated apoptosis. This was further supported by the finding that IFN treatment enhanced Fas-mediated caspase-8 activation, one of the earliest signaling events downstream receptor activation. In addition, IFN treatment attenuated the interleukin 6 (IL-6)-dependent activation of signal transducer and activator of transcription 3 (Stat3), interfering with a known survival pathway in MM that has previously been linked with resistance to Fas-mediated apoptosis. Taken together, our results show that IFN-induced up-regulation of Fas sensitizes MM cells to Fas-mediated apoptosis and suggest that attenuation of Stat3 activation may be a potentially important event in this process.

Two scenarios for future pig meat production were constructed. The first was a "business as usual" scenario, where the pig feed was based on domestic grain and imported soy-meal, and no efforts were made to reduce pesticide use. The second scenario had a strong environmental focus, and both peas and rapeseed were grown at pig-farm level to produce grain and protein feed. Preventive measures, such as a more diverse crop rotation and mechanical weed control, were combined to reduce pesticide use. The two scenarios were environmentally assessed by Life Cycle Assessment (LCA) and a pesticide risk indicator model (PRI-Farm). The results showed environmentally sound possibilities to reduce pesticide dependency and risks by using altered plant protection strategies in pig-feed production. Organizing on-farm feed production so that protein feed crops are integrated with grain crops contributes to a more diverse crop rotation.

Interleukin 8 (IL-8) is a chemotactic cytokine involved in the recruitment and activation of neutrophils as well as in cell proliferation and angiogenesis. Because these events are essential components of folliculogenesis, ovulation, and subsequent repair of the ruptured follicle, the presence and regulation of IL-8 in the human follicle of the menstrual cycle was investigated. The concentrations of IL-8 were higher in follicular fluids from dominant follicles of late follicular/ovulatory phase compared with those of midfollicular phase. IL-8 was detected in the media from cultured granulosa and theca cells, with 10-fold higher levels in the theca cell cultures. Exposure to FSH and LH increased the IL-8 secretion from granulosa cells, but no effect was seen in theca cell cultures. Estradiol and progesterone did not affect IL-8 secretion from any cell type. The cytokines IL-1alpha and IL-1beta, but not tumor necrosis factor alpha, enhanced IL-8 secretion from both cell types. IL-8 levels in cultures of granulosa-lutein cells from hyperstimulated in vitro fertilization cycles were not affected by either gonadotropins or steroids. These data provide evidence that ovarian IL-8 is gonadotropin and cytokine induced and may be involved in the hormonally regulated stages of follicular development and ovulation.