Revealing the role of land-use features on macrolitter distribution in Swiss freshwaters.

Macrolitter, especially macroplastics, (> 0.5 cm) negatively impact freshwater ecosystems, where they can be retained along lake shores, riverbanks, floodplains or bed sediments. Long-term and large-scale assessments of macrolitter on riverbanks and lake shores provide an understanding of litter abundance, composition, and origin in freshwater systems. Combining macrolitter quantification with hydrometeorological variables allows further study of leakage, transport, and accumulation characteristics. Several studies have explored the role of hydrometeorological factors in influencing macrolitter distribution and found that river discharge, runoff, and wind only partially explains its distribution. Other factors, such as land-use features, have not yet been thoroughly investigated. In this study, we provide a country-scale assessment of land-use influence on macrolitter abundance in freshwater systems. We analyzed the composition of the most commonly found macrolitter items (referred to as 'top items', n = 42,565) sampled across lake shores and riverbanks in Switzerland between April 2020 and May 2021. We explored the relationship between eleven land-use features and macrolitter abundance at survey locations (n = 143). The land-use features included buildings, city centers, public infrastructure, recreational areas, forests, marshlands, vineyards, orchards, other land, and rivers and canals. The majority of top items are significantly and positively correlated with land-use features related to urban coverage, notably roads and buildings. Over 60% of top items were found to be correlated with either roads or buildings. Notably, tobacco, food and beverage-related products, as well as packaging and sanitary products, showed strong associations with these urban land-use features. Other types of items, however, did not exhibit a relationship with land-use features, such as industry and construction-related items. Ultimately, this highlights the need to combine measures at the local and regional/national scales for effective litter reduction.

Retro-miRs: novel and functional miRNAs originating from mRNA retrotransposition.

BACKGROUND: Reverse-transcribed gene copies (retrocopies) have emerged as major sources of evolutionary novelty. MicroRNAs (miRNAs) are small and highly conserved RNA molecules that serve as key post-transcriptional regulators of gene expression. The origin and subsequent evolution of miRNAs have been addressed but not fully elucidated. RESULTS: In this study, we performed a comprehensive investigation of miRNA origination through retroduplicated mRNA sequences (retro-miRs). We identified 17 retro-miRs that emerged from the mRNA retrocopies. Four of these retro-miRs had de novo origins within retrocopied sequences, while 13 retro-miRNAs were located within exon regions and duplicated along with their host mRNAs. We found that retro-miRs were primate-specific, including five retro-miRs conserved among all primates and two human-specific retro-miRs. All retro-miRs were expressed, with predicted and experimentally validated target genes except miR-10527. Notably, the target genes of retro-miRs are involved in key biological processes such as metabolic processes, cell signaling, and regulation of neurotransmitters in the central nervous system. Additionally, we found that these retro-miRs play a potential oncogenic role in cancer by targeting key cancer genes and are overexpressed in several cancer types, including liver hepatocellular carcinoma and stomach adenocarcinoma. CONCLUSIONS: Our findings demonstrated that mRNA retrotransposition is a key mechanism for the generation of novel miRNAs (retro-miRs) in primates. These retro-miRs are expressed, conserved, have target genes with important cellular functions, and play important roles in cancer.

Association between post-operative delirium and use of volatile anesthetics in the elderly: A real-world big data approach.

STUDY OBJECTIVE: Early post-operative delirium is a common perioperative complication in the post anesthesia care unit. To date it is unknown if a specific anesthetic regime can affect the incidence of delirium after surgery. Our objective was to examine the effect of volatile anesthetics on post-operative delirium. DESIGN: Single Center Observational Study. SETTING: Post Anesthesia Care Units at a German tertiary medical center. PATIENTS: 30,075 patients receiving general anesthesia for surgery. MEASUREMENTS: Delirium was assessed with the Nursing Delirium Screening Scale at the end of the recovery period. Subgroup-specific effects of volatile anesthetics on post-operative delirium were estimated using generalized-linear-model trees with inverse probability of treatment weighting. We further assessed the age-specific effect of volatiles using logistic regression models. MAIN RESULTS: Out of 30,075 records, 956 patients (3.2%) developed delirium in the post anesthesia care unit. On average, patients who developed delirium were older than patients without delirium. We found volatile anesthetics to increase the risk (Odds exp. (B) for delirium in the elderly 1.8-fold compared to total intravenous anesthesia. Odds increases with unplanned surgery 3.0-fold. In the very old (87 years or older), the increase in delirium is 6.2-fold. This result was confirmed with internal validation and in a logistic regression model. CONCLUSIONS: Our exploratory study indicates that early postoperative delirium is associated with the use of volatile anesthetics especially in the sub-cohort of patients aged 75 years and above. Further studies should include both volatile and intravenous anesthetics to find the ideal anesthetic in elderly patients.

Research priorities for the pan-Canadian Oncology Symptom Triage and Remote Support practice guides: a modified nominal group consensus.

Introduction: The pan-Canadian Oncology Symptom Triage and Remote Support (costars) team is studying how to improve the quality and consistency of cancer symptom management. Methods: A 1-day invitational meeting was held 24 October 2017 in Ottawa, Ontario, to review the current evidence from costars projects and to establish research priorities for a future largescale implementation study. The meeting included 36 participants who were clinicians from adult oncology, pediatric oncology, and homecare; policymakers from national, provincial, and regional organizations; researchers; and a patient. Half the day involved summarizing evidence from four costars studies and experiences with implementing the costars symptom practice guides. The second half of the day used a modified nominal group technique to generate research questions within small groups, presentation of research questions to all participants, and two rounds of voting to reach consensus on research priorities. Results: Participants proposed 4 research categories:■ User-centred augmentation to enhance usability (for example, designing a mobile costars solution)■ Outcome measurement (for example, determining key competencies for clinicians)■ Regular renewal of costars to keep pace with evolving evidence (for example, updates for novel therapies)■ Integration into clinical practice (for example, meaningful engagement of patients and caregivers in study design). Conclusions: Across categories, the top 3 priorities were effect on health services use, competency development, and a mobile costars solution. Future research will address identified priorities, reflecting the needs and perspectives of diverse stakeholders. Stakeholder collaboration will continue to guide our approach to operationalizing this priority research agenda.

[Surgical treatment of tracheopleural and bronchopleural fistulas after bronchoplastic resection (sleeve or bifurcation resection)]. / Chirurgische Versorgung tracheo-/bronchopleuraler Fisteln nach bronchoplastischer Resektion (Manschetten­/Bifurkationsresektion).

The treatment of tracheopleural and bronchopleural fistulas at an anastomosis after sleeve resection is complex and fraught with complications. Morbidity and mortality are very high. Therefore, great care must be taken to avoid such complications. The clinical signs and the early diagnosis of a potentially critical anastomosis or anastomotic leakage as well as the treatment, including secondary pneumonectomy are presented.

Factors influencing the use by radiation therapists of cancer symptom guides: a mixed-methods study.

Background: Radiation therapists play an important role in helping patients to safely manage and triage potentially life-threatening symptoms. The purpose of the present study was to assess factors influencing the use by radiation therapists of evidence-informed symptom practice guides for patients experiencing cancer treatment-related symptoms. Methods: In a mixed-methods descriptive study guided by the Knowledge-to-Action framework, interviews and a barriers survey were conducted. Two independent reviewers conducted a content analysis of interview transcripts. Barriers survey data were analyzed using frequency distributions and univariate descriptive statistics. Open-ended data from the surveys underwent content analysis and were triangulated with interview findings. Results: Of 90 radiation therapists approached, 58 completed the survey (64%), and 14 were interviewed. Of the 98% who reported providing symptom management to patients undergoing radiation treatment, 53% used evidence-informed practice guidelines. Radiation therapists had moderate moral norms (4.6 of 7) and beliefs about the consequences of using costars (pan-Canadian Oncology Symptom Triage and Remote Support) practice guides (4.8), but neutral intention (3.4) and beliefs about their own capabilities (3.9). Environmental barriers included lack of time (2.0), lack of access (2.5), and neutral organizational support (3.0). Radiation therapists identified a need for training (5.5). Common unique barriers to practice guide use were lack of time during radiation treatments, unclear fit with scope of practice, disparate focus on site-specific symptoms, and lack of medication knowledge. Conclusions: The symptom practice guides were perceived by the radiation therapists to benefit patients, enhance their own knowledge of symptom management, and promote consistent practice. Additional work is required to identify the scope of practice of radiation therapists within the interprofessional team.

Effect of Intraoperative Single-Shot Application of Vancomycin in Liver Transplant Recipients on Postoperative Infections With Enterococcus faecium and Enterococcus faecalis.

OBJECTIVES: Infections are major causes of morbidity and mortality in the early postoperative period after liver transplant. We observed a high rate of enterococcal infections at our center. Therefore, we added an intraoperative single shot of vancomycin to the standard regimen of meropenem given over 5 days. The aim of this study was to determine the prevalence of both Enterococcus faecium and Enterococcus faecalis infections during the first 28 days after surgery depending on the type of antibiotic prophylaxis and their implications on mortality and morbidity. MATERIALS AND METHODS: Our retrospective cohort analysis included 179 patients: 93 patients received meropenem only and 86 patients were treated with meropenem plus vancomycin. RESULTS: During the first 28 days after transplant, microbiological tests showed that 51 patients (28.5%) were positive for Enterococcus faecium and 25 patients (14.0%) were positive for Enterococcus faecalis. Enterococcus faecium infections appeared significantly more often in patients without vancomycin (P = .013). In the second week after transplant, there was a significant reduction in Enterococcus faecium infections in the meropenem plus vancomycin group (P = .015). Enterococcus faecalis infections occurred more often in the patients receiving meropenem alone, but results were not statistically significant (P = .194). There was a trend toward more frequent renal replacement therapy in the meropenem plus vancomycin group. We found no differences between the groups regarding survival after 1 and 2 years, length of hospital stay, or duration in the intensive care unit. Overall 1-year survival was 78.8% (141/179 patients). CONCLUSIONS: Although postoperative Enterococcus species infections can be reduced after liver transplant by adding vancomycin to the intraoperative antibiotic regimen, it does not improve the long-term outcomes.

Metabolic plasticity in CLL: adaptation to the hypoxic niche.

Metabolic transformation in cancer is increasingly well understood. However, little is known about the metabolic responses of cancer cells that permit their survival in different microenvironments. We have used a nuclear magnetic resonance based approach to monitor metabolism in living primary chronic lymphoid leukemia (CLL) cells and to interrogate their real-time metabolic responses to hypoxia. Our studies demonstrate considerable metabolic plasticity in CLL cells. Despite being in oxygenated blood, circulating CLL cells are primed for hypoxia as measured by constitutively low level hypoxia-inducible factor (HIF-1α) activity and modest lactate production from glycolysis. Upon entry to hypoxia we observed rapid upregulation of metabolic rates. CLL cells that had adapted to hypoxia returned to the 'primed' state when re-oxygenated and again showed the same adaptive response upon secondary exposure to hypoxia. We also observed HIF-1α independent differential utilization of pyruvate in oxygenated and hypoxic conditions. When oxygenated, CLL cells released pyruvate, but in hypoxia imported pyruvate to protect against hypoxia-associated oxidative stress. Finally, we identified a marked association of slower resting glucose and glutamine consumption, and lower alanine and lactate production with Binet A0 stage samples indicating that CLL may be divided into tumors with higher and lower metabolic states that reflect disease stage.

Patterns of early resuscitation associated with mortality after penetrating injuries.

BACKGROUND: Penetrating injuries are rare in European populations so their management represents a particular challenge. The aim was to assess early therapeutic aspects that are associated with favourable outcomes in patients with penetrating trauma. METHODS: Patients with penetrating injuries documented from 2009 to 2013 in the TraumaRegister DGU® were analysed. Patients with a primary admission and an Injury Severity Score (ISS) of at least 9 were included. The Revised Injury Severity Classification (RISC) II score was used for mortality prediction, and a standardized mortality ratio (SMR) calculated per hospital. Hospitals with favourable outcome (SMR below 1) were compared with those with poor outcome (SMR 1 or more). RESULTS: A total of 50 centres had favourable outcome (1242 patients; observed mortality rate 15.7 per cent) and 34 centres had poor outcome (918 patients; observed mortality rate 24.4 per cent). Predicted mortality rates according to RISC-II were 20.4 and 20.5 per cent respectively. Mean(s.d.) ISS values were 22(14) versus 21(14) (P = 0.121). Patients in the favourable outcome group had a significantly shorter time before admission to hospital and a lower intubation rate. They received smaller quantities of intravenous fluids on admission to the emergency room, but larger amounts of fresh frozen plasma, and were more likely to receive haemostatic agents. A higher proportion of patients in the favourable outcome group were treated in a level I trauma centre. Independent risk factors for hospital death following penetrating trauma identified by multivariable analysis included gunshot injury mechanism and treatment in non-level I centres. CONCLUSION: Among penetrating traumas, gunshot injuries pose an independent risk of death. Treatment of penetrating trauma in a level I trauma centre was significantly and independently associated with lower hospital mortality.

[Review of the Literature for Interpretation of Endobronchial Wound Healing after Tracheobronchial Sleeve Resection]. / Literaturbasierte Empfehlung zur bronchoskopischen Interpretation einer Anastomose nach Manschettenresektion.

Sleeve resection comprises 3.1 % to 27.7 % of all anatomic lung resections performed in Germany. Anastomotic insufficiency is a feared complication that should be avoided. When anastomotic insufficiency does lead to secondary pneumonectomy, postoperative morbidity and mortality is high (30 % to 80 %). It is therefore very important to standardize the technique of sleeve resection as well as postoperative care. The time-point of postoperative follow-up and the interpretation of endobronchial healing have not yet been defined. In this paper anastomotic healing is described and interpreted with the help of a 5-step classification that allows bronchoscopic evaluation and classification of the anastomosis. The aim is to provide a standardized algorithm for postoperative care after sleeve resection. The basis of this classification and postoperative care measures derived from it are described and illustrated with the help of clinical examples.

Mucosal relapse of visceral leishmaniasis in a child treated with anti-TNFα.

Visceral leishmaniasis is an enzootic parasitosis present across the Mediterranean Basin. Some consider it an opportunistic parasite. We report the case of a girl treated with anti-tumour necrosis factor alpha (anti-TNFα) for juvenile idiopathic arthritis who had previously presented with visceral leishmaniasis. Two and a half years later, she presented a tumour-like mass in the nasal mucous membrane caused by Leishmania parasites. Leishmania infantum is classically responsible for visceral leishmaniasis, but pure mucocutaneous leishmaniasis has also been described. To our knowledge, this is the first observation of a recurrence of visceral leishmaniasis in the mucocutaneous form. The occurrence of atypical forms and presentations in those on anti-TNF therapy should be considered.

[Potentially curative surgical therapy in oligometastatic non-small cell lung cancer]. / Potenziell kurative chirurgische Therapie beim oligometastasierten nicht-kleinzelligen Lungenkarzinom.

Lung cancer is a leading cause of cancer related death worldwide. Non-small cell lung cancer (NSCLC) represents 85 % of all lung cancer cases and approximately 40 % of all patients impress with a metastatic disease at the time of diagnosis. Stage IV NSCLC has a poor prognosis and is incurable. The recommended standard therapy in this case is a palliative supportive systemic chemotherapy. However, a distinctive subgroup of patients with stage IV NSCLC appear clinically with an oligometastatic disease and may qualify for surgical therapy. There is evidence that patients with synchronous or metachronus solitary satellite nodules, either located intrapulmonary or extrapulmonary, benefit from surgical resection.

Toroidal-spiral particles for codelivery of anti-VEGFR-2 antibody and irinotecan: a potential implant to hinder recurrence of glioblastoma multiforme.

Heterogeneous toroidal-spiral particles (TSPs) were generated by polymer droplet sedimentation, interaction, and cross-linking. TSPs provide a platform for encapsulation and release of multiple compounds of different sizes and physicochemical properties. As a model system, we demonstrate the encapsulation and independently controlled release of an anti-VEGFR-2 antibody and irinotecan for the treatment of glioblastoma multiforme. The anti-VEGFR-2 antibody was released from the TS channels and its binding to HUVECs was confirmed by confocal microscopy and flow cytometry, suggesting active antibody encapsulation and release. Irinotecan, a small molecule drug, was released from the dense polymer matrix of poly(ethylene glycol) diacrylate (MW ~ 700 g/mol; PEGDA 700). Released irinotecan inhibited the proliferation of U251 malignant glioma cells. Since the therapeutic compounds are released through different pathways, specifically diffusion through the polymer matrix versus TS channels, the release rate can be controlled independently through the design of the structure and material of particle components.

Freestyle root replacement for complex destructive aortic valve endocarditis.

OBJECTIVES: In destructive aortic valve endocarditis with abscess formation in the root, homografts are used more often than xenografts. Because we had reliable perioperative results with Freestyle (Medtronic Inc, Minneapolis, Minn) xenograft root replacement in these complex patients, we analyzed the long-term outcome in this high-risk indication. METHODS: Of 126 consecutive patients with aortic valve endocarditis treated by surgery from 1997 to 2012, 32 (25.4%) received a Freestyle aortic root replacement for severe, destructive valve endocarditis and were studied retrospectively with approval of the local ethical committee. Perioperative complications, recurrence of endocarditis, and long-term morbidity and mortality were analyzed. The follow-up period was 3 months to 11.5 years. RESULTS: Indication for surgery was native (n = 9) and prosthetic valve endocarditis (n = 23). In 18 patients, concomitant procedures were performed: coronary bypass (n = 9), additional valve surgery (n = 6), and ascending aortic surgery (n = 7). Thirty-day mortality was 19.4% (n = 6). There were no instances of technical failure requiring modification of the surgical strategy or reoperation for anastomotic bleeding. Actuarial survival at 5 and 10 years was 61.9% and 54.2%, respectively. Freedom from death, reoperation for prostheses dysfunction, and recurrence of endocarditis as the composite end point at 5 and 10 years was 56.3% and 53.1%, respectively. CONCLUSIONS: The Freestyle root was used successfully with no technical complications in all patients with most severe destructive aortic root endocarditis. In view of this complex patient population, short- and long-term results make this conduit a reliable choice for treatment of this condition.

Simple adaptations of surgical technique to critically reduce the risk of postoperative sternal complications in patients receiving bilateral internal thoracic arteries.

OBJECTIVES: Limited blood supply to the thoracic chest wall is a known risk factor for sternal wound complications after CABG. Therefore, bilateral internal thoracic arteries are still rarely utilized despite their proven superior graft patency. The aim of our study was to analyse whether modification of the surgical technique is able to limit the risk of sternal wound complications in patients receiving bilateral internal thoracic artery grafting. METHODS: All 418 non-emergent CABG patients receiving bilateral internal thoracic artery CABG procedures (BITA) from January 2001 to January 2012 were analysed for sternal wound complications. Surgical technique together with known risk factors and relevant comorbidity were analysed for their effect on the occurrence of sternal wound complications by means of multivariate logistic regression analysis. RESULTS: Sternal wound complications occurred in 25 patients (5.9%), with a sternal dehiscence rate of 2.4% (10 patients). In multivariate analysis, diabetes (odds ratio [OR]: 4.8, 95% CI: 1.9-11.7, P=0.001), but not obesity (OR: 1.6, 95% CI: 0.7-4.2, P=0.28) or chronic obstructive pulmonary disease (OR: 2.2, 95% CI: 0.87-5.6, P=0.1) was a relevant comorbid condition for sternal complications. Skeletonization of ITA grafts (OR: 0.17, 95% CI: 0.06-0.5, P=0.001) and the augmented use of sternal wires (OR: 0.24, 95% CI: 0.06-0.95, P=0.04) were highly effective in preventing sternal complications. The use of platelet-enriched-fibrin glue (PRF) sealant, however, was associated with more superficial sternal infections (OR: 3.7, 95% CI: 1.3-10.5, P=0.02). CONCLUSIONS: Adjusted for common risk factors, skeletonization of BITA grafts together with augmented sternal wires is effective in preventing sternal complications. The use of PRF sealant, however, increased the risk for superficial wound complications.

In human glioblastomas transcript elongation by alternative polyadenylation and miRNA targeting is a potent mechanism of MGMT silencing.

Favorable outcome after chemotherapy of glioblastomas cannot unequivocally be linked to promoter hypermethylation of the O6-methylguanine-DNA methyltransferase (MGMT) gene encoding a DNA repair enzyme associated with resistance to alkylating agents. This indicates that molecular mechanisms determining MGMT expression have not yet been fully elucidated. We here show that glioblastomas are capable to downregulate MGMT expression independently of promoter methylation by elongation of the 3'-UTR of the mRNA, rendering the alternatively polyadenylated transcript susceptible to miRNA-mediated suppression. While the elongated transcript is poorly expressed in normal brain, its abundance in human glioblastoma specimens is inversely correlated with MGMT mRNA expression. Using a bioinformatically guided experimental approach, we identified miR-181d, miR-767-3p, and miR-648 as significant post-transcriptional regulators of MGMT in glioblastomas; the first two miRNAs induce MGMT mRNA degradation, the latter affects MGMT protein translation. A regression model including the two miRNAs influencing MGMT mRNA expression and the MGMT methylation status reliably predicts The Cancer Genome Atlas MGMT expression data. Responsivity of MGMT expressing T98G glioma cells to temozolomide was significantly enhanced after transfection of miR-181d, miR-767-3p, and miR-648. Taken together, our results uncovered alternative polyadenylation of the MGMT 3'-UTR and miRNA targeting as new mechanisms of MGMT silencing.

Minimally invasive mitral valve reconstruction on the fibrillating heart for high-risk patients.

BACKGROUND AND AIM OF THE STUDY: Mitral valve surgery after previous cardiac surgery is technically demanding and risky. In patients after coronary artery bypass grafting (CABG), mitral valve surgery is associated with a high risk of injury to the bypass graft with concomitant myocardial ischemia. An aortic valve prosthesis usually severely impairs access to the mitral valve, so that these patients are often denied surgery. Furthermore, patients with porcelain aorta may be inoperable. METHODS: A series of 10 patients undergoing minimally invasive mitral valve repair via a right-sided anterolateral minithoracotomy without aortic cross-clamping on the fibrillating heart was investigated. Four patients had an aortic valve prosthesis in situ, six patients had undergone previous CABG, and two patients presented with porcelain aorta. RESULTS: Reconstruction was possible in nine patients. Cannulation was performed femorally in three patients, and via the axillary artery in seven patients. No fatalities were observed. One patient required rethoracotomy for bleeding and subsequently developed a right-sided pneumonia, and a second patient experienced lower-limb ischemia. The postoperative course of the other eight patients was uneventful. No patient presented with significant residual mitral insufficiency at control echocardiography. CONCLUSION: Minimally invasive mitral valve reconstruction via a right-sided minithoracotomy represents an attractive surgical option in a high-risk reoperative setting.