Occurrence and trends of Clostridioides difficile infections in hospitalized patients: a prospective multi-centre cohort study in six German university hospitals, 2016-2020.

BACKGROUND: For Clostridioides difficile infections (CDIs) in Germany no longitudinal multi-centre studies with standardized protocols for diagnosing CDI are available. Recent evaluations of general surveillance databases in Germany indicate a downward trend in CDI rates. We aimed to describe the actual burden and trends of CDI in German university hospitals from 2016 to 2020. METHODS: Our study was a prospective multi-centre study covering six German university hospitals. We report the data in total, stratified by year, by medical specialty as well as by CDI severity. Multi-variable regression analyses were performed to assess risk factors for severe CDI. RESULTS: We registered 3780 CDI cases among 1,436,352 patients. The median length of stay (LOS) of CDI cases was 20 days (interquartile range 11-37) compared with a general LOS of 4.2 days. In-hospital all-cause mortality in CDI patients was 11.7% (N = 444/3780), while mortality attributed to CDI was 0.4% (N = 16/3761). CDI recurrence rate was comparatively low at 7.2%. The incidence density of severe healthcare-associated healthcare onset (HAHO)-CDI showed a significant decrease from 2.25/10,000 patient days (pd) in 2016 to 1.49/10,000 pd in 2020 (trend calculation P=0.032). CONCLUSIONS: Compared with a European point-prevalence study in 2013/2014, where overall CDI incidence density was 11.2 cases/10,000 pd in Germany (EUCLID), we see in our study halved overall CDI rates of 5.6 cases/10,000 pd in 2020. Our study shows current data on the distribution of CDI cases in German university hospitals and thus provides international comparative data on the key indicators of CDI.

[Lung transplantation: current situation and developments]. / Lungentransplantation: aktueller Stand und Entwicklungen.

Lung transplantation is currently the gold standard treatment for end-stage lung diseases. Advances in the preservation of donor lungs, the surgical technique and immunosuppressive therapy have led to lung transplantation now being a routine procedure. Nevertheless, the shortage of donor organs, the acute and particularly chronic lung allograft dysfunction (CLAD) still represent major challenges even in experienced centers. Research in this area is still necessary to improve the long-term survival of lung recipients.

Predictors of recurrence following laparoscopic minor hepatectomy for hepatocellular carcinoma in the UK.

AIMS: Minor hepatectomy, which is increasingly carried out laparoscopically (LLR), is a cornerstone of curative treatment for hepatocellular carcinoma (HCC). The majority of relevant publications however originate from regions with endemic viral hepatitis. Although the incidence of HCC in the UK is increasing, little is known about outcomes following LLR. METHODS: Consecutive patients undergoing minor (involving ≤2 segments) LLR or open resection (OLR) at our institute between 2014 and 2021 were compared. Selection from a plethora of factors potentially impacting on overall (OS) and disease free survival (DFS) was optimised with Lasso regression. To enable analysis of patients having repeat resection, multivariate frailty modelling was utilised to calculate hazard ratios (HR). RESULTS: The analysis of 111 liver resections included 55 LLR and 56 OLR. LLR was associated with a shorter hospital stay (5 ± 2 vs. 7 ± 2 days; p < 0.001) and a lower comprehensive complication index (4.43 vs. 9.96; p = 0.006). Mean OS (52.3 ± 2.3 vs. 49.9 ± 3.0 months) and DFS (33.9 ± 3.4 vs. 36.5 ± 3.6 months; p = 0.59) were comparable between LLR and OLR, respectively (median not reached). Presence of mixed cholangiocarcinoma/HCC, satellite lesions and AFP level predicted OS and DFS. In addition tumour size was predictive of DFS. CONCLUSIONS: In the studied population minor LLR was associated with shorter hospital stay and fewer complications while offering non-inferior long-term outcomes. A number of predictors for disease free survival have been elucidated that may aid in identifying patients with a high risk of disease recurrence and need for further treatment.

Kerr Enhanced Backaction Cooling in Magnetomechanics.

Optomechanics is a prime example of light matter interaction, where photons directly couple to phonons, allowing the precise control and measurement of the state of a mechanical object. This makes it a very appealing platform for testing fundamental physics or for sensing applications. Usually, such mechanical oscillators are in highly excited thermal states and require cooling to the mechanical ground state for quantum applications, which is often accomplished by using optomechanical backaction. However, while massive mechanical oscillators are desirable for many tasks, their frequency usually decreases below the cavity linewidth, significantly limiting the methods that can be used to efficiently cool. Here, we demonstrate a novel approach relying on an intrinsically nonlinear cavity to backaction-cool a low frequency mechanical oscillator. We experimentally demonstrate outperforming an identical, but linear, system by more than 1 order of magnitude. Furthermore, our theory predicts that with this approach we can also surpass the standard cooling limit of a linear system. By exploiting a nonlinear cavity, our approach enables efficient cooling of a wider range of optomechanical systems, opening new opportunities for fundamental tests and sensing.

Associations between prenatal exposure to power plants and birth outcomes across the United States.

OBJECTIVES: Although there is growing evidence that in utero exposure to power plants increases the risk of adverse birth outcomes, studies have focused on coal-fired plants and single US locations, limiting generalizability. We used birth certificate data from 50 states and DC to examine the associations between prenatal exposure to power plants and birth outcomes overall and by race/ethnicity. METHODS: We linked 2009-2018 county-level microdata natality files on 34,674,911 singleton births from 50 states and DC with 9-month county-level averages of power plant fuel consumption based on month/year of birth. We estimated linear regression models for birth weight and gestational age and probit models for the dichotomous outcomes of low birth weight, small for gestational age (SGA), and preterm birth. We subsequently examined interactions between plant fuel consumption and race/ethnicity. RESULTS: Overall, 69.1% of counties had any power plant fuel consumption. Although we found no overall effects of prenatal exposure to power plants on birth weight or SGA, a significant interaction (both P < 0.01) revealed that a 10% increase in fuel consumption was associated with infants born to White women having slightly lower birth weights (1.76 g; 95% confidence interval = -2.87, -0.65) and higher risk of being born SGA (0.0002; 95% confidence interval = 0.0002, 0.0002). CONCLUSION: Power plants have negative effects on infant health, which exist independent of locality.

Primary school mobile dental program in New South Wales, Australia: protocol for the evaluation of a state government oral health initiative.

BACKGROUND: Socioeconomically disadvantaged children are disproportionately affected by oral disease. Mobile dental services help underserved communities overcome barriers to accessing health care, including time, geography, and trust. The NSW Health Primary School Mobile Dental Program (PSMDP) is designed to provide diagnostic and preventive dental services to children at their schools. The PSMDP is mainly targeted toward high-risk children and priority populations. This study aims to evaluate the program's performance across five local health districts (LHDs) where the program is being implemented. METHODS: The evaluation will use routinely collected administrative data, along with other program-specific data sources, from the district public oral health services to conduct a statistical analysis that determines the reach and uptake of the program, its effectiveness, and the associated costs and cost-consequences. The PSMDP evaluation program utilises data from Electronic Dental Records (EDRs) and other data sources, including patient demographics, service mix, general health, oral health clinical data and risk factor information. The overall design includes cross-sectional and longitudinal components. The design combines comprehensive output monitoring across the five participating LHDs and investigates the associations between socio-demographic factors, service patterns and health outcomes. Time series analysis using difference-in-difference estimation will be conducted across the four years of the program, involving services, risk factors, and health outcomes. Comparison groups will be identified via propensity matching across the five participating LHDs. An economic analysis will estimate the costs and cost-consequences for children who participate in the program versus the comparison group. DISCUSSION: The use of EDRs for oral health services evaluation research is a relatively new approach, and the evaluation works within the limitations and strengths of utilising administrative datasets. The study will also provide avenues to improve the quality of data collected and system-level improvements to better enable future services to be aligned with disease prevalence and population needs.

Evaluation of treatment delays in hepatopancreatico-biliary surgery during the first COVID-19 wave.

INTRODUCTION: The COVID-19 pandemic has caused oncological services worldwide to face unprecedented challenges resulting in treatment disruption for surgical patients. Hepatopancreatico-biliary (HPB) cancers are characterised by rapid disease progression. This study aims to assess delays in receiving surgery for this patient cohort during the first COVID-19 wave. METHODS: Patients undergoing surgery between April and July 2020 (COVID-19 period) were compared with a control group from the preceding year. Delay in receiving surgery was defined as more than 50 days between referral and surgery date. Statistical analysis was carried out to evaluate predictors of delay and short-term outcomes. RESULTS: During the COVID-19 and pre-COVID-19 periods, 94 and 115 patients underwent surgery, respectively. No patients contracted COVID-19 postoperatively. Some 118 patients waited more than 50 days for surgery versus 91 who received surgery within 50 days from referral. Independent predictors for surgical delay were undergoing surgery in the COVID-19 era (odds ratio (OR) 2.2, 95% confidence interval (CI) 1.2-4.1; p=0.015), referral pathway (OR 35.1, 95% CI 4.2-296; p=0.001) and presenting pathology (OR 8.3, 95% CI 1.2-56.1; p=0.03). Short-term outcomes were comparable between groups. CONCLUSIONS: Patient referral pathway and presenting pathology may contribute to delays in undergoing HPB cancer surgery during COVID-19 outbreaks. It is hoped that a better understanding of these factors will aid in designing shifts in healthcare policy during future pandemic outbreaks.

Enhancing Ground-State Population and Macroscopic Coherence of Room-Temperature WS_{2} Polaritons through Engineered Confinement.

Exciton polaritons (polaritons herein) in transition-metal dichalcogenide monolayers have attracted significant attention due to their potential for polariton-based optoelectronics. Many of the proposed applications rely on the ability to trap polaritons and to reach macroscopic occupation of their ground energy state. Here, we engineer a trap for room-temperature polaritons in an all-dielectric optical microcavity by locally increasing the interactions between the WS_{2} excitons and cavity photons. The resulting confinement enhances the population and the first-order coherence of the polaritons in the ground state, with the latter effect related to dramatic suppression of disorder-induced inhomogeneous dephasing. We also demonstrate efficient population transfer into the trap when optically injecting free polaritons outside of its periphery.

Crossover from exciton-polariton condensation to photon lasing in an optical trap.

Optical trapping has been proven to be an effective method of separating exciton-polariton condensates from the incoherent high-energy excitonic reservoir located at the pumping laser position. This technique has significantly improved the coherent properties of exciton-polariton condensates, when compared to a quasi-homogeneous spot excitation scheme. Here, we compare two experimental methods on a sample, where a single spot excitation experiment allowed us only to observe photonic lasing in the weak coupling regime. In contrast, the ring-shaped excitation resulted in the two-threshold behavior, where an exciton-polariton condensate manifests itself at the first and photon lasing at the second threshold. Both lasing regimes are trapped in an optical potential created by the pump. We interpret the origin of this confining potential in terms of repulsive interactions of polaritons with the reservoir at the first threshold and as a result of the excessive free-carrier induced refractive index change of the microcavity at the second threshold. This observation offers a way to achieve multiple phases of photonic condensates in samples, e.g., containing novel materials as an active layer, where two-threshold behavior is impossible to achieve with a single excitation spot.

Strategies for keeping dairy cows and calves together - a cross-sectional survey study.

Although it is still most common to rear dairy calves separately from adult cattle, the interest in prolonged contact between dairy calves and lactating cows during early life is increasing. Previous research has documented positive effects of cow-calf contact (CCC) on for example early calf growth and udder health of suckled cows, but also negative effects such as increased separation distress and reduced weight gains after weaning. The aim of this study was to use information from European farms with prolonged cow-calf contact to identify innovative solutions to common challenges for CCC farms. Commercial dairy farms that kept calves with adult lactating cows for seven days or more after birth were invited to participate, and interviews were performed with 104 farmers from six countries. During interviews, information about farm management, calf rearing, farmers' perception of animal health on their farm, and farmers' drivers and barriers for implementing CCC were collected. We found that CCC was practised in a large variety of housing and management systems, and that calves could be reared together with their dam, with foster cows, or using a combination of the two. The contact period varied considerably (7-305 days) between farms and about 25% of the farms manually milk fed the calves during parts of the milk feeding period. Daily contact time varied between farms, from 30 minutes per day to permanent contact except at milking. Behaviours indicative of separation distress, most commonly vocalisation in cows and calves, were reported by 87% of the farmers. Strategies to alleviate separation distress, for example simultaneous gradual weaning and separation, were used on some farms. Building constraints were most often mentioned as a barrier for implementing CCC. Our findings suggest that CCC is practised in a variety of commonly used husbandry systems. Reported challenges were primarily related to weaning and separation, and to building constraints; these aspects should be areas of future research.

Decellularization of Wharton's Jelly Increases Its Bioactivity and Antibacterial Properties.

The field of regenerative medicine has recently seen an emerging trend toward decellularized extracellular matrix (ECM) as a biological scaffold for stem cell-delivery. Human umbilical cord represents a valuable opportunity from both technical and ethical point of view to obtain allogenic ECM. Herein, we established a protocol, allowing the full removal of cell membranes and nuclei moieties from Wharton's jelly (WJ) tissue. No alterations in the ECM components (i.e., collagen, GAG content, and growth factors), physical (i.e., porosity and swelling) and mechanical (i.e., linear tensile modulus) properties were noticed following WJ processing. Furthermore, no effect of the tissue processing on macromolecules and growth factors retention was observed, assuring thus a suitable bioactive matrix for cell maintenance upon recellularization. Based on the in vitro and in vivo biodegradability and stromal cell homing capabilities, decellularized WJ could provide an ideal substrate for stromal cells adhesion and colonization. Interestingly, the tissue processing increased the antibacterial and antiadhesive properties of WJ against Staphylococcus aureus and Staphylococcus epidermidis pathogens. Altogether, our results indicate that decellularized WJ matrix is able to limit Staphylococcus-related infections and to promote stromal cell homing, thus offering a versatile scaffold for tissue regenerative medicine.

Technical feasibility and clinical evaluation of 4D-MRI guided liver SBRT on the MR-linac.

PURPOSE: Image-guided stereotactic body radiation therapy (SBRT) is an important local treatment for liver metastases. MRI-guidance enables direct tumor visualization, eliminating fiducial marker implantation. The purpose of this study was to test technical feasibility of our 4D-MRI guided liver SBRT workflow. Additionally, intra-fraction target motion and consequent target-coverage were studied. MATERIALS & METHODS: Patients with liver metastases were included in this sub-study of the prospective UMBRELLA-II clinical trial. Patients received mid-position (midP) SBRT. The daily adapt-to-position workflow included localization, verification and intra-fraction tumor midP monitoring using 4D-MRI. Technical feasibility was established based on persistence of the treatment protocol, treatment time ≤1 h, no geographical miss and no unexpected acute toxicity grade >3. All 4D-MRIs were registered to the planning midP-CT and tumor midP and amplitude were calculated. Additionally, delivered target dose was accumulated incorporating the 4D-MRI intra-fraction tumor motion and evaluated with Monte-Carlo error simulations. RESULTS: 20 patients with liver metastases were included and treated with 4D-MRI guided SBRT. Feasibility criteria were met in all-but-one patient. No grade ≥3 acute toxicity was observed. Group mean (M), systematic and random midP-drifts were 2.4 mm, 2.6 mm and 3.1 mm in CC-direction. 4D-MRI tumor CC-amplitudes were reduced compared to the simulation 4D-CT (M = -1.9 mm) and decreased during treatment (M = -1.4 mm). Dose accumulation showed adequate target-coverage on a population level. CONCLUSION: We successfully demonstrated technical feasibility of 4D-MRI guided SBRT in a cohort of 20 patients with liver metastases. However, substantial midposition drifts occurred which stress the need for intra-fraction motion management strategies to further increase the precision of treatment delivery.

[Epidemiology and surgical treatment of pancreatic cancer in the State of Brandenburg : Analysis of 5418 cases]. / Epidemiologie und operative Behandlung des Pankreaskarzinoms im Flächenland Brandenburg : Analyse von 5418 Fällen.

BACKGROUND: Pancreatic cancer is the second most frequent cause of death among all forms of cancer in Germany with more than 19,000 deaths per year. The evaluation of the nationwide clinical cancer register aims to depict the reality of treatment and to improve the quality of treatment in the future by targeted analyses. METHOD: The data from the clinical cancer register of Brandenburg-Berlin for the diagnosis years 2001-2017 were analyzed with respect to the treatment of pancreatic cancer. Data from patients resident in the State of Brandenburg were evaluated with respect to epidemiological and therapeutic parameters. RESULTS: A total of 5418 patients with pancreatic cancer were documented in the register from 2001 to 2017 and 49.6% of the patients were diagnosed as having the Union for International Cancer Control (UICC) stage IV. A pancreas resection was carried out in 26.4% of the cases. In cases of cancer of the head of the pancreas the most frequent procedure was a pylorus-preserving resection with 51.8% and a pancreatectomy was carried out in 9.4%. The R0 resection rate of all pancreatic cancers in the period from 2014 to 2017 was 61.9%. After R0 resection the 5­year survival was 19%. Relevant multivariate survival factors were age, UICC stage and the residual (R) tumor classification. The case numbers per hospital had no influence on the absolute survival of patients operated on in the State of Brandenburg. CONCLUSION: The treatment reality in the State of Brandenburg for patients with pancreatic cancer corresponds to the results of international publications with respect to the key performance indicators investigated. A qualitative internationally comparable treatment of these patients is also possible in nonmetropolitan regions.

Effect of transcutaneous electrical nerve stimulation (TENS) on knee pain and physical function in patients with symptomatic knee osteoarthritis: the ETRELKA randomized clinical trial.

OBJECTIVE: To determine the effectiveness of TENS at relieving pain and improving physical function as compared to placebo TENS, and to determine its safety, in patients with knee osteoarthritis. METHODS: Multi-centre, parallel, 1:1 randomized, double-blind, placebo-controlled clinical trial conducted in six outpatient clinics in Switzerland. We included 220 participants with knee osteoarthritis recruited between October 15, 2012, and October 15, 2014. Patients were randomized to 3 weeks of treatment with TENS (n = 108) or placebo TENS (n = 112). Our pre-specified primary endpoint was knee pain at the end of 3-weeks treatment assessed with the WOMAC pain subscale. Secondary outcome measures included WOMAC physical function subscale and safety outcomes. RESULTS: There was no difference between TENS and placebo TENS in WOMAC pain at the end of treatment (mean difference -0.06; 95%CI -0.41 to 0.29; P = 0.74), nor throughout the trial duration (P = 0.98). Subgroup analyses did not indicate an interaction between patient/treatment characteristics and treatment effect on WOMAC pain at the end of treatment (P-interaction ≥0.22). The occurrence of adverse events was similar across groups, with 10.4% and 10.6% of patients reporting events in the TENS and placebo TENS groups, respectively (P = 0.95). No relevant differences were observed in secondary outcomes. CONCLUSIONS: TENS does not improve knee osteoarthritis pain when compared to placebo TENS. Therapists should consider other potentially more effective treatment modalities to decrease knee osteoarthritis pain and facilitate strengthening and aerobic exercise. Our findings are conclusive and further trials comparing TENS and placebo TENS in this patient population are not necessary.