Short-term Outcomes of Robotic Versus Open Pancreatoduodenectomy: Propensity Score-matched Analysis.

OBJECTIVE: The goal of the current study was to investigate the perioperative outcomes of robotic pancreaticoduodenectomy (RPD) and open pancreaticoduodenectomy (OPD) in a high-volume center. BACKGROUND: Despite RPDs prospective advantages over OPD, current evidence comparing the 2 has been limited and has prompted further investigation. The aim of this study was to compare both approaches while including the learning curve phase for RPD. METHODS: A 1:1 propensity score-matched analysis of a prospective database of RPD with OPD (2017-2022) at a high-volume center was performed. The main outcomes were overall- and pancreas-specific complications. RESULTS: Of 375 patients who underwent PD (OPD n=276; RPD n=99), 180 were included in propensity score-matched analysis (90 per group). RPD was associated with less blood loss [500 (300-800) vs 750 (400-1000) mL; P =0.006] and more patients without a complication (50% vs 19%; P <0.001). Operative time was longer [453 (408-529) vs 306 (247-362) min; P <0.001]; in patients with ductal adenocarcinoma, fewer lymph nodes were harvested [24 (18-27) vs 33 (27-39); P <0.001] with RPD versus OPD. There were no significant differences for major complications (38% vs 47%; P =0.291), reoperation rate (14% vs 10%; P =0.495), postoperative pancreatic fistula (21% vs 23%; P =0.858), and patients with the textbook outcome (62% vs 55%; P =0.452). CONCLUSIONS: Including the learning phase, RPD can be safely implemented in high-volume settings and shows potential for improved perioperative outcomes versus OPD. Pancreas-specific morbidity was unaffected by the robotic approach. Randomized trials with specifically trained pancreatic surgeons and expanded indications for the robotic approach are needed.

The radiomorphological appearance of the invasive margin in pancreatic cancer is associated with tumor budding.

PURPOSE: Pancreatic cancer (PDAC) is characterized by infiltrative, spiculated tumor growth into the surrounding non-neoplastic tissue. Clinically, its diagnosis is often established by magnetic resonance imaging (MRI). At the invasive margin, tumor buds can be detected by histology, an established marker associated with poor prognosis in different types of tumors. METHODS: We analyzed PDAC by determining the degree of tumor spiculation on T2-weighted MRI using a 3-tier grading system. The grade of spiculation was correlated with the density of tumor buds quantified in histological sections of the respective surgical specimen according to the guidelines of the International Tumor Budding Consensus Conference (n = 28 patients). RESULTS: 64% of tumors revealed intermediate to high spiculation on MRI. In over 90% of cases, tumor buds were detected. We observed a significant positive rank correlation between the grade of radiological tumor spiculation and the histopathological number of tumor buds (rs = 0.745, p < 0.001). The number of tumor buds was not significantly associated with tumor stage, presence of lymph node metastases, or histopathological grading (p ≥ 0.352). CONCLUSION: Our study identifies a readily available radiological marker for non-invasive estimation of tumor budding, as a correlate for infiltrative tumor growth. This finding could help to identify PDAC patients who might benefit from more extensive peripancreatic soft tissue resection during surgery or stratify patients for personalized therapy concepts.

The presence of an aberrant anterior tibial artery does not depend on the patient's morphotype.

PURPOSE: The aberrant anterior tibial artery (ATA) runs along the posterior surface of the tibial cortex making it, particularly, at risk during high tibial osteotomy (HTO). This study aimed to analyze the prevalence of the ATA according to global morphotype and its anatomical features in consideration of knee surgery. METHODS: This retrospective study included 1589 knees on magnetic resonance imaging (MRI) studies with long-leg radiographs. The anatomical characteristics of the ATA, its distance in surgical areas at risk and its lumen were defined on MRI. Its presence according to the patient's morphotype (varus, valgus or neutral) was assessed using a χ2 test. RESULTS: The ATA was present in 33 of 1589 knees, resulting in a prevalence of 2.1%. The anteroposterior distance of the ATA to the tibial head was 6.6 ± 2.5 mm at the height of the tibial plateau, 2.7 ± 1.6 mm at the footprint of the posterior cruciate ligament and 1.0 ± 0.6 mm under the top of the fibula (p < 0.01). For these three levels, the ratio between the distance from the ATA to the lateral tibial border and the total tibial width decreases progressively (p < 0.001). The mean lumen area of the ATA was 4.2 ± 2.5 mm2, and the lumen of the popliteal artery was 9.2 ± 3.6 mm2, representing a ratio of 49.4 ± 27.0%. The prevalence of ATA was similar between varus and valgus patients (n.s). CONCLUSION: The presence of an ATA is rare, found in one out of 50 cases, but can be easily identified on MRI in patients before knee surgery, especially before HTO. The patient's morphotype did not influence its presence, the lumen diameter is highly variable and its clinical impact has yet to be determined. STUDY DESIGN: Cross-sectional study. LEVEL OF EVIDENCE: Level 3.

Higher conversion rate to knee arthroplasty in female patients following medial open-wedge high tibial osteotomy.

PURPOSE: Most studies about medial open-wedge high tibial osteotomy (HTO) reported outcomes without focusing on gender differences. Therefore, the study compared the long-term survival rate and postoperative subjective knee function after HTO in female versus male patients with symptomatic medial compartment knee osteoarthritis. METHODS: The data of three cohorts with long-term outcomes were analysed (n = 245; 32% females; age: 49 ± 7 years; Kellgren Lawrence Grade I 6.1%, II 32.7%, III 42.4%; IV 18.8%). The minimum follow-up was at least 6 years or an earlier conversion to total knee arthroplasty (TKA). The gender-specific survival rate after HTO was calculated after 5 and 10 years and compared using Kaplan-Meier analysis and the logrank test. Baseline characteristics and subjective knee function (International Knee Documentation Committee [IKDC]/Lysholm) were analysed between both genders. RESULTS: Forty of 78 (51.3%) women and 41 of 167 men (24.5%) underwent TKA. HTO survival in females was significantly lower (p = 0.0010). The 5- and 10-year survival rates were 85.9% and 62.6% for females and 93.4% and 77.7% for males. In females and males, from preoperative to the last follow-up, the IKDC (43 ± 15 to 58 ± 17; 47 ± 14 to 67 ± 18) and the Lysholm (42 ± 18 to 72 ± 18; 55 ± 22 to 77 ± 23) improved significantly (all p < 0.0001). Females had significantly lower preoperative and postoperative IKDC (p = 0.0438; p = 0.0035) and Lysholm scores (p = 0.0002; p = 0.0323). But the absolute improvements of the IKDC and Lysholm were not significantly different between genders. CONCLUSIONS: Females had higher conversion rates to TKA and lower knee function at the last follow-up. However, preoperative knee function was lower in females and the absolute improvement following HTO was similar for both genders. In general, females benefit from HTO to treat medial knee arthritis, and TKA could be postponed for half of female patients for more than 10 years. However, surgeons must be aware of the described inferior outcomes in females for realistic patient expectation management. LEVEL OF EVIDENCE: Level II.

IL-17A-producing CD8+ T cells promote PDAC via induction of inflammatory cancer-associated fibroblasts.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is characterised by an abundant desmoplastic stroma composed of cancer-associated fibroblasts (CAF) and interspersed immune cells. A non-canonical CD8+ T-cell subpopulation producing IL-17A (Tc17) promotes autoimmunity and has been identified in tumours. Here, we evaluated the Tc17 role in PDAC. DESIGN: Infiltration of Tc17 cells in PDAC tissue was correlated with patient overall survival and tumour stage. Wild-type (WT) or Il17ra-/- quiescent pancreatic stellate cells (qPSC) were exposed to conditional media obtained from Tc17 cells (Tc17-CM); moreover, co-culture of Tc17-CM-induced inflammatory (i)CAF (Tc17-iCAF) with tumour cells was performed. IL-17A/F-, IL-17RA-, RAG1-deficient and Foxn1nu/nu mice were used to study the Tc17 role in subcutaneous and orthotopic PDAC mouse models. RESULTS: Increased abundance of Tc17 cells highly correlated with reduced survival and advanced tumour stage in PDAC. Tc17-CM induced iCAF differentiation as assessed by the expression of iCAF-associated genes via synergism of IL-17A and TNF. Accordingly, IL-17RA controlled the responsiveness of qPSC to Tc17-CM. Pancreatic tumour cells co-cultured with Tc17-iCAF displayed enhanced proliferation and increased expression of genes implicated in proliferation, metabolism and protection from apoptosis. Tc17-iCAF accelerated growth of mouse and human tumours in Rag1-/- and Foxn1nu/nu mice, respectively. Finally, Il17ra-expressed by fibroblasts was required for Tc17-driven tumour growth in vivo. CONCLUSIONS: We identified Tc17 as a novel protumourigenic CD8+ T-cell subtype in PDAC, which accelerated tumour growth via IL-17RA-dependent stroma modification. We described a crosstalk between three cell types, Tc17, fibroblasts and tumour cells, promoting PDAC progression, which resulted in poor prognosis for patients.

Celiac Axis Stenosis is an Underestimated Risk Factor for Increased Morbidity After Pancreatoduodenectomy.

OBJECTIVE: To assesses the prevalence and severity of CAS in patients undergoing PD/total pancreatectomy and its association with major postoperative complications after PD. SUMMARY OF BACKGROUND DATA: CAS may increase the risk of ischemic complications after PD. However, the prevalence of CAS and its relevance to major morbidity remain unknown. METHODS: All patients with a preoperative computed tomography with arterial phase undergoing partial PD or TP between 2014 and 2017 were identified from a prospective database. CAS was assessed based on computed tomography and graded according to its severity: no stenosis (<30%), grade A (30%-<50%), grade B (50%-≤80%), and grade C (>80%). Postoperative complications were assessed and uni- and multivariable risk analyses were performed. RESULTS: Of 989 patients, 273 (27.5%) had CAS: 177 (17.9%) with grade A, 83 (8.4%) with grade B, and 13 (1.3%) with grade C. Postoperative morbidity and 90-day mortality occurred in 278 (28.1%) patients and 41 (4.1%) patients, respectively. CAS was associated with clinically relevant pancreatic fistula ( P =0.019), liver perfusion failure ( P =0.003), gastric ischemia ( P =0.001), clinically relevant biliary leakage ( P =0.006), and intensive care unit ( P =0.016) and hospital stay ( P =0.001). Multivariable analyses confirmed grade B and C CAS as independent risk factors for liver perfusion failure; in addition, grade C CAS was an independent risk factor for clinically relevant pancreatic fistula and gastric complications. CONCLUSIONS: CAS is common in patients undergoing PD. Higher grade of CAS is associated with an increased risk for clinically relevant complications, including liver perfusion failure and postoperative pancreatic fistula. Precise radiological assessment may help to identify CAS. Future studies should investigate measures to mitigate CAS-associated risks.

Low bone mineral density is a prognostic factor for elderly patients with HCC undergoing TACE: results from a multicenter study.

OBJECTIVES: Low bone mineral density (BMD) was recently identified as a novel risk factor for patients with hepatocellular carcinoma (HCC). In this multicenter study, we aimed to validate the role of BMD as a prognostic factor for patients with HCC undergoing transarterial chemoembolization (TACE). METHODS: This retrospective multicenter trial included 908 treatment-naïve patients with HCC who were undergoing TACE as a first-line treatment, at six tertiary care centers, between 2010 and 2020. BMD was assessed by measuring the mean Hounsfield units (HUs) in the midvertebral core of the 11th thoracic vertebra, on contrast-enhanced computer tomography performed before treatment. We assessed the influence of BMD on median overall survival (OS) and performed multivariate analysis including established estimates for survival. RESULTS: The median BMD was 145 HU (IQR, 115-175 HU). Patients with a high BMD (≥ 114 HU) had a median OS of 22.2 months, while patients with a low BMD (< 114 HU) had a lower median OS of only 16.2 months (p < .001). Besides albumin, bilirubin, tumor number, and tumor diameter, BMD remained an independent prognostic factor in multivariate analysis. CONCLUSIONS: BMD is an independent predictive factor for survival in elderly patients with HCC undergoing TACE. The integration of BMD into novel scoring systems could potentially improve survival prediction and clinical decision-making. KEY POINTS: • Bone mineral density can be easily assessed in routinely acquired pre-interventional computed tomography scans. • Bone mineral density is an independent predictive factor for survival in elderly patients with HCC undergoing TACE. • Thus, bone mineral density is a novel imaging biomarker for prognosis prediction in elderly patients with HCC undergoing TACE.

Co-Exposure of Phenanthrene and the cyp-Inducer 3-Methylchrysene Leads to Altered Biotransformation and Increased Toxicity in Fish Egg and Larvae.

Polycyclic aromatic hydrocarbons (PAHs) have frequently been suspected of governing crude oil toxicity because of similar morphological defects in fish. However, PAH concentrations are often not high enough to explain the observed crude oil toxicity. We hypothesize that one PAH can enhance the metabolism and toxicity of another PAH when administered as a mixture. Early life stage Atlantic haddock (Melanogrammus aeglefinus) were in this study exposed to phenanthrene in the presence and absence of 3-methylchrysene that is known to induce the metabolic enzyme cytochrome P450 1A via cyp1a gene expression. Uptake, metabolism, and multiple toxicity endpoints were then measured in a time-course study up to 3 days post-hatching. Passive dosing provided aqueous concentrations ≈180 µg/L for phenanthrene and ≈0.6 µg/L for 3-methylchrysene, which resulted in tissue concentrations ≈60 µg/g ww for phenanthrene and ≈0.15 µg/g ww for 3-methylchrysene. The low concentration of 3-methylchrysene led to the elevated expression of cyp1a but no toxicity. Levels of phenanthrene metabolites were 5-fold higher, and morphological defects and cardiotoxicity were consistently greater when co-exposed to both compounds relative to phenanthrene alone. This work highlights the metabolic activation of PAH toxicity by a co-occurring PAH, which can lead to excess toxicity, synergistic effects, and the overproportional contribution of PAHs to crude oil toxicity.

Lymphoepithelial cyst of the pancreas: can common imaging features help to avoid resection?

BACKGROUND: Differentiation of cystic pancreatic neoplasms remains a challenging task for radiologists regarding the main aim of identifying malignant and premalignant lesions. PURPOSE: The study aimed to compare the radiological features of lymphoepithelial cysts (LEC) with other cystic pancreatic lesions, which could help to differentiate them in order to avoid unnecessary resection. MATERIAL AND METHODS: We retrospectively reviewed 10 cases of resected and histopathologically confirmed LECs during a 12-year period with available imaging studies; 20 patients with mucinous cystic neoplasms (MCN), 20 patients with branch-duct intraductal papillary mucinous neoplasms (BD-IPMN), and 20 patients with serous cystic neoplasms (SCN) were selected to serve as control groups. Imaging findings as well as clinical data were analyzed. RESULTS: The following imaging morphology of LEC was identified: simple cystic appearance (20%) and mixed cystic-solid appearance (80%) with either a diffuse subsolid component (30%) or mural nodule(s) (50%). All lesions revealed exophytic location with a strong male predominance (9:1). MCNs occurred exclusively in middle-aged women, IPMN in both sexes showed slight male predominance (13:7), and SCN showed female predominance (5:15). Median patient age in LEC (48.5, IQR 47-54.5) was significantly younger compared to IPMN (p < 0.001) and SCN (p = 0.02). Unenhanced CT attenuation of LEC was higher than MCNs (p = 0.025) and IPMNs (p = 0.021), showing no significant difference to SCN (p = 0.343). CONCLUSION: The present study provides key radiological features of LEC for the differentiation from other cystic pancreatic lesions such as increased CT attenuation in the unenhanced phase, absence of a connection to the main pancreatic duct (MPD), and exophytic location. In addition to these imaging features, clinical data, such as male predominance in LEC, must be considered for the differentiation of cystic pancreatic lesions.

Biodegradation of chemicals tested in mixtures and individually: mixture effects on biodegradation kinetics and microbial composition.

Biodegradation in the aquatic environment occurs in the presence of many chemicals, while standard simulation biodegradation tests are conducted with single chemicals. This study aimed to investigate the effect of the presence of additional chemicals on (1) biodegradation kinetics of individual chemicals and (2) the microbial composition in test systems. Parallel mixture and single substance experiments were conducted for 9 chemicals (phenethyl benzoate, oxacycloheptadec-10-en-2-one, α-ionone, methyl 2-naphthyl ether, decan-5-olide, octan-2-one, 2'-acetonaphthanone, methyl N-methylanthranilate, (+)-menthone) using inoculum from a Danish stream. Biotic and abiotic test systems were incubated at 12 °C for 1-30 days. Primary biodegradation kinetics were then determined from biotic/abiotic peak area ratios using SPME GC/MS analysis. The effect of the mixture on biodegradation varied with test chemical and was more pronounced for chemicals with lag-phases above 14 days: two chemicals degraded in the mixture but not when tested alone (i.e., positive mixture effect), and two degraded when tested alone but not in the mixture (i.e., negative mixture effect). Microbial composition (16S rRNA gene amplicon sequencing) was highly affected by 14 days incubation and the presence of the mixture (significant carbon source), but less by single chemicals (low carbon source). Growth on chemical mixtures resulted in consistent proliferation of Pseudomonas and Malikia, while specific chemicals increased the abundance of putative degraders belonging to Novosphingobium and Zoogloea. The chemical and microbiological results support (1) that simulation biodegradation kinetics should be determined in mixtures at low environmentally relevant concentrations and (2) that degradation times beyond some weeks are associated with more uncertainty.

Double level osteotomy for medial osteoarthritis and bifocal varus malalignment has excellent short-term results while maintaining physiologic radiographic joint parameters.

PURPOSE: The purpose of this study was to prospectively evaluate the clinical and radiological results of double level osteotomy (distal femoral lateral closed wedge and proximal tibial medial open wedge) in medial osteoarthritis and varus malalignment due to bifocal deformity of femur and tibia. METHODS: From 2017 to 2019 all cases of DLO in osteoarthritic varus malaligned knees with bifocal deformity (femoral and tibial deformity) were prospectively enrolled into this observational therapeutic study. Evaluation was performed preoperatively, at six, twelve, 18 and 24 months with regard to survival (not requiring arthroplasty), functional outcome [subjective International Knee Documentation Committee score (IKDC), Oxford Knee Score (OKS), Knee Injury and Osteoarthritis Outcome score (KOOS) and Tegner Activity Scale], pain level (numeric rating scale), subjective satisfaction (rating 1-5), radiographic parameters on a pre-and postoperative full leg x-rays (mechanical axis, mechanical proximal tibial and distal femoral angles) and complications. For statistical evaluation student's t test, Mann-Whitney U test and Wilcoxon-signed-rank test were used. RESULTS: Fifty-two consecutive cases in 48 patients were enrolled in the study. Three cases were excluded, resulting in a follow-up rate of 94%. No arthroplasties were performed within follow-up. All functional outcome scores substantially and significantly increased as early as six months after the index procedure and further increased until final follow-up (p < 0.001). Pain level significantly decreased (p < 0.001). At final follow-up all patients stated that they would retrospectively undergo the operation again, and rated the result with 4.5 ± 0.6 out of 5 (3-5). Radiographic parameters were within physiological limits postoperatively. No severe complications occurred. CONCLUSIONS: Double level osteotomy has excellent short-term results while maintaining physiological radiographic parameters. Therefore, it should be an integral part and standard procedure in realignment surgery for monocompartimental osteoarthritis. LEVEL OF EVIDENCE: IV (prospective observational therapeutic study).

High prevalence of increased posterior tibial slope in ACL revision surgery demands a patient-specific approach.

PURPOSE: To determine the prevalence of an "increased posterior tibial slope (PTS)" (PTS ≥ 12°) in a population with one, two or ≥ three anterior cruciate ligament (ACL) graft insufficiencies. Furthermore, to investigate whether the prevalence of an increased PTS and the absolute PTS increases with an increasing number of ACL graft insufficiencies, as well as to determine the survival time of the first ACL graft. METHODS: Patients diagnosed with an ACL graft insufficiency between January 2021 and March 2022 were included. The PTS was measured using the proximal anatomical tibial axis on long lateral knee radiographs. Patients were divided into 3 groups depending on the number of ACL graft insufficiencies: group A (1 graft insufficiency), group B (2 graft insufficiencies) and group C (≥ 3 graft insufficiencies). The prevalence of increased PTS and absolute PTS between groups was compared alongside the survival of the first ACL graft between patients with or without increased PTS. RESULTS: Two-hundred and six patients (147 males/59 females) met the inclusion criteria. 73 patients showed an increased PTS [prevalence 35% [95% confidence interval (CI) (29%; 42%)]. 155 patients were found in category A, 42 patients in B and 9 patients in C. The prevalence of increased PTS for group A, B and C was, 32% [95% CI (25%; 40%)], 38% [95% CI (23%; 53%)] and 78% [95% CI (51%; 100%)], respectively. The prevalence of increased PTS and mean PTS did not increase significantly between group A and B. However, both parameters increased significantly between group A and C, and group B and C (p < 0.05). The survival time of the first ACL graft in patients with or without an increased PTS was 3 (interquartile range (IQR) 5) and 6 years (IQR 9), respectively (p < 0.05). CONCLUSION: There is a 35% prevalence of increased PTS in the studied ACL graft insufficient patient cohort. The survival of the first ACL graft is shorter in patients with an increased PTS. Surgeons should be aware of the high prevalence of increased PTS when consulting patients for revision ACL reconstruction as it is an important risk factor for recurrent instability.

Gastric Venous Congestion After Total Pancreatectomy is Frequent and Dangerous.

OBJECTIVE: The aim of this study was to determine the role of GVC in mortality after TP. BACKGROUND: Data from a nationwide administrative database revealed that TP is associated with a 23% mortality rate in Germany. Methods: A total of 585 consecutive patients who had undergone TP (n = 514) or elective completion pancreatectomy (n = 71) between January 2015 and December 2019 were analyzed. Univariable and multivariable analyses were performed to identify risk factors for GVC and 90-day mortality. Results: GVC was observed in 163 patients (27.9%) requiring partial or total gastrectomy. Splenectomy (odds ratio 2.14, 95% confidence interval 1.253.80, P = 0.007) and coronary vein resection (odds ratio 5.49,95% confidence interval 3.19-9.64, P < 0.001) were independently associated with GVC. The overall 90-day mortality after TP was 4.1% (24 of 585 patients), 7.4% in patients with GVC and 2.8% in those without GVC ( P = 0.014). Of the 24 patients who died after TP, 12 (50%) had GVC. CONCLUSION: GVC is a frequent albeit not well-known finding after TP, especially when splenectomy and resection of the coronary vein are performed. Adequate decision making for partial gastrectomy during TP is crucial. Insufficient gastric venous drainage after TP is life-threatening.

Biodegradation Kinetics of Fragrances, Plasticizers, UV Filters, and PAHs in a Mixture─Changing Test Concentrations over 5 Orders of Magnitude.

Biodegradation of organic chemicals emitted to the environment is carried out by mixed microbial communities growing on multiple natural and xenobiotic substrates at low concentrations. This study aims to (1) perform simulation type biodegradation tests at a wide range of mixture concentrations, (2) determine the concentration effect on the biodegradation kinetics of individual chemicals, and (3) link the mixture concentration and degradation to microbial community dynamics. Two hundred ninety-four parallel test systems were prepared using wastewater treatment plant effluent as inoculum and passive dosing to add a mixture of 19 chemicals at 6 initial concentration levels (ng/L to mg/L). After 1-30 days of incubation at 12 °C, abiotic and biotic test systems were analyzed using arrow solid phase microextraction and GC-MS/MS. Biodegradation kinetics at the highest test concentrations were delayed for several test substances but enhanced for the reference chemical naphthalene. Test concentration thus shifted the order in which chemicals were degraded. 16S rRNA gene amplicon sequencing indicated that the highest test concentration (17 mg C/L added) supported the growth of the genera Acidovorax, Novosphingobium, and Hydrogenophaga, whereas no such effect was observed at lower concentrations. The chemical and microbial results confirm that too high mixture concentrations should be avoided when aiming at determining environmentally relevant biodegradation data.

Screening of Antimicrobial Activity of Essential Oils against Bovine Respiratory Pathogens - Focusing on Pasteurella multocida.

Administration of essential oils as natural plant products with antimicrobial activity might be an alternative to antibiotic treatment of bovine respiratory disease. The aim of this study was to analyse the in vitro antimicrobial activity of 11 essential oils against Pasteurella multocida isolated from the respiratory tract of calves using microdilution with determination of minimum inhibitory and bactericidal concentration as well as agar disc diffusion. Additionally, antimicrobial activity against Mannheimia haemolytica and bacteria in the Mannheimia clade was assessed by agar disc diffusion. Seven essential oil mixtures were also tested against all bacterial isolates. P. multocida was strongly inhibited by cinnamon cassia and lemongrass oil followed by coriander, winter savory, thyme, clove, and peppermint oil in the microdilution assays. Eucalyptus, wintergreen, spruce, and star anise oil showed lower activity. Comparison of both methods revealed an underestimation of cinnamon cassia oil activity by agar disc diffusion and conflicting results for wintergreen oil in microdilution, which precipitated in broth. Cinnamon cassia, thyme, wintergreen, lemongrass, and winter savory oil all showed strong antimicrobial activity against M. haemolytica. Bacteria in the Mannheimia clade were mostly inhibited by cinnamon cassia and thyme oil. Pasteurella isolates were more susceptible to inhibition by essential oils than Mannheimia isolates. Essential oil mixtures did not show stronger antibacterial activity than single essential oils. In conclusion, cinnamon cassia and lemongrass as well as coriander, winter savory, and thyme oil are promising candidates for treatment of P. multocida-associated bovine respiratory infections.

Presentation and outcome of mixed neuroendocrine non-neuroendocrine neoplasms of the pancreas.

BACKGROUND/OBJECTIVES: Mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN) of the pancreas and periampullary region are extremely rare and heterogeneous malignancies. Literature is sparse, clinical management is not standardized and little is known about survival outcomes. The aim of this study was to identify pathological and radiological features of MiNEN and assess the outcome of surgical management. METHODS: Patients undergoing surgery for pancreatic and periampullary MiNEN between 2001 and 2019 were retrospectively analysed based on a prospective database. Histological, radiological and clinical features were assessed. Survival was analysed in a nested case-control study and matched-pair analyses with pure neuroendocrine neoplasms (pNEN) and ductal adeno- or acinar cell carcinomas of the pancreas. A literature review with focus on survival after surgical resection was additionally performed. RESULTS: Of 13 patients with MiNEN, 5 had acinar-MiNEN and 8 adeno-MiNEN. Two of 5 (40%) acinar-MiNEN and one adeno-MiNEN patients had liver metastases. All but one adeno-MiNEN (88%) showed preoperative radiological features of pancreatic adenocarcinoma, 3 of 5 (60%) acinar-MiNEN exhibited mainly neuroendocrine features. No surgical mortality was observed. The 5-year overall survival rate in all MiNEN was 40%. Five-year survival rate was 58% in adeno-MiNEN and comparable to that of matched ductal adenocarcinomas (36%) and pNEN (48%). Five-year overall survival rate was 20% in acinar-MiNEN, compared to 39% in acinar carcinoma patients and 59% in matched pNEN patients. CONCLUSIONS: MiNEN are rare and difficult to distinguish from pure adenocarcinoma or neuroendocrine neoplasm preoperatively. Surgical resection would therefore be the treatment of choice in localized tumors.

Passive Dosing of Petroleum and Essential Oil UVCBs-Whole Mixture Toxicity Testing at Controlled Exposure.

Petroleum products and essential oils are produced and used in large amounts and are categorized as "Substances of Unknown or Variable composition, Complex reaction products or Biological materials (UVCBs)." These UVCBs are notorious difficult-to-test substances, since they are complex mixtures of hydrophobic and volatile compounds. This study introduces two passive dosing (PD) approaches for whole UVCB toxicity testing: (1) headspace PD applies the UVCB and purified lipid oil as a donor to control exposure via the headspace and (2) silicone rod PD applies UVCB-loaded silicone rods to control exposure via an aqueous test medium and headspace. Headspace gas chromatography-mass spectrometry measurements were used to cross-validate the approaches at the saturation level and to confirm exposure and maintain mixture composition at varying donor concentration levels. Both approaches were applied to whole-mixture toxicity tests of petroleum and essential oil UVCBs with daphnia and algae. Finally, the observed toxicity was linked to concentrations in the donor and in lipid membranes at equilibrium with the donors. Dose-response curves were similar across the dosing approaches and tested species for petroleum products but differed by an order of magnitude between essential oils and PD systems. All observed toxic effects were consistent with baseline toxicity, and no excess mixture toxicity was observed.

Combining Headspace Solid-Phase Microextraction with Internal Benchmarking to Determine the Elimination Kinetics of Hydrophobic UVCBs.

Substances classified as unknown or variable composition, complex reaction products or biological origin (UVCB) present a challenge for environmental hazard and risk assessment. Here, we present a novel approach for whole-substance bioconcentration testing applied to cedarwood oil-an essential oil composed of volatile, hydrophobic organic chemicals. The method yields whole-body elimination rate constants for a mixture of constituents. Our approach combines in vivo dietary fish exposure with internal benchmarking and headspace solid-phase microextraction (HS-SPME) equilibrium sampling followed by suspect-screening analysis. We quantified depuration rate constants of 13 individual cedarwood oil constituents based on relative peak areas using gas chromatography (GC) coupled with Orbitrap-mass spectrometry (MS) and GC triple-quadrupole (QqQ)-MS. For seven constituents with available analytical standards, we compared the rate constants to the results obtained from solvent extraction, clean-up, and targeted GC-MS analysis. The HS-SPME sampling approach allowed for automated sample extraction and analyte enrichment while minimizing evaporative losses of the volatile target analytes and reducing matrix interferences from low-volatility organics. The suspect-screening analysis enabled the quantification of constituents without available analytical standards, while the internal benchmarking significantly reduced variability from differences in delivered dose and analytical variability between the samples.

Determining the Temperature Dependency of Biodegradation Kinetics for 34 Hydrocarbons while Avoiding Chemical and Microbial Confounding Factors.

Biodegradation kinetics data are keystone for evaluating the environmental persistence and risk of chemicals. Biodegradation kinetics depend highly on the prevailing temperature, which influences microbial community structures, metabolic rates, and chemical availability. There is a lack of high-quality comparative biodegradation kinetics data that are determined at different test temperatures but with the same microbial inoculum and chemical availability. The present study was designed to determine the effect of test temperature on the biodegradation kinetics of hydrocarbons while avoiding confounding factors. We used inocula from a Northern river (2.7 °C) and a Central European river (12.5 °C). Aqueous stock solutions containing 45 individual hydrocarbons were generated by passive dosing and added to river water containing the native microorganisms. Compound-specific biodegradation kinetics were then determined at 2.7, 12, and 20 °C based on substrate depletion. Main findings comprise the following: (1) Degradation half-times (DegT50) of 34 test chemicals were determined at different test temperatures and were largely consistent with the Arrhenius equation (activation energy, 65.4 kJ/mol). (2) Differences in biodegradation kinetics between tested isomers were rather limited. (3) The recent lowering of standard test temperature from 20 to 12 °C results typically in a doubling of DegT50 values and can lead to a stricter persistency assessment.

The effects of nitroxide structure upon 1H Overhauser dynamic nuclear polarization efficacy at ultralow-field.

The efficacy in 1H Overhauser dynamic nuclear polarization in liquids at ultralow magnetic field (ULF, B0 = 92 ± 0.8 µT) and polarization field (Bp = 1-10 mT) was studied for a broad variety of 26 different spin probes. Among others, piperidine, pyrrolidine, and pyrroline radicals specifically synthesized for this study, along with some well-established commercially available nitroxides, were investigated. Isotope-substituted variants, some sterically shielded reduction-resistant nitroxides, and some biradicals were included in the measurements. The maximal achievable enhancement, Emax, and the radio frequency power, P1/2, needed for reaching Emax/2 were measured. Physico-chemical features such as molecular weight, spectral linewidth, heterocyclic structure, different types of substituents, deuteration, and 15N-labeling as well as the difference between monoradicals and biradicals were investigated. For the unmodified nitroxide radicals, the Emax values correlate with the molecular weight. The P1/2 values correlate with the spectral linewidth and are additionally influenced by the type of substituents neighboring the nitroxide group. The nitroxide biradicals with high intramolecular spin-spin coupling show low performance. Nitroxides enriched with 15N and/or 2H afford significantly higher |Emax| and require lower power to do so, compared to their unmodified counterparts containing at natural abundance predominantly 14N and 1H. The results allow for a correlation of chemical features with physical hyperpolarization-related properties and indicate that small nitroxides with narrow spectral lines have clear advantages for the use in Overhauser dynamic nuclear polarization experiments. Perdeuteration and 15N-labeling can be used to additionally boost the spin probe performance.