Multiscale and multimodal imaging for three-dimensional vascular and histomorphological organ structure analysis of the pancreas.

Exocrine and endocrine pancreas are interconnected anatomically and functionally, with vasculature facilitating bidirectional communication. Our understanding of this network remains limited, largely due to two-dimensional histology and missing combination with three-dimensional imaging. In this study, a multiscale 3D-imaging process was used to analyze a porcine pancreas. Clinical computed tomography, digital volume tomography, micro-computed tomography and Synchrotron-based propagation-based imaging were applied consecutively. Fields of view correlated inversely with attainable resolution from a whole organism level down to capillary structures with a voxel edge length of 2.0 µm. Segmented vascular networks from 3D-imaging data were correlated with tissue sections stained by immunohistochemistry and revealed highly vascularized regions to be intra-islet capillaries of islets of Langerhans. Generated 3D-datasets allowed for three-dimensional qualitative and quantitative organ and vessel structure analysis. Beyond this study, the method shows potential for application across a wide range of patho-morphology analyses and might possibly provide microstructural blueprints for biotissue engineering.

Comparison between intrauterine application of an antibiotic and an herbal product to treat clinical endometritis in dairy cattle - A randomized multicentre field study.

Uterine diseases are main indications for antibiotic use in dairy cows. To test a non-antibiotic treatment option, we compared the effect of an intrauterine cephapirin (Metricure®; cefapirin benzathin 500 mg per dosis; CEPH) with an intrauterine applied herbal product (25 ml of EucaComp® PlantaVet containing alcoholic extracts of Calendula officinalis L., Mellissa officinalis L., Origanum majorana L. and Eucalyptus globulus Labill. (EUC)) on the clinical cure of endometritis. Examinations of 816 cows between 21 and 35 days after calving were performed and cases of clinical endometritis (n = 169) were included. Diagnosis based on a scoring system for vaginal discharge. Study animals were randomly assigned to one of two treatment groups and treated immediately. After excluding animals with incomplete datasets, 136 cows (EUC: n = 61; CEPH: n = 75) remained for the final analysis. In total, 64% (EUC: 61%, CEPH: 67%) of analysed endometritis cases were considered as clinically cured 14 ± 2 days after the first treatment, 15% stayed uncured after the application of a maximum of two consecutive treatments, leading to an overall clinical cure rate of 85% (EUC: 82%, CEPH: 88%). No statistically difference in clinical cure rates could be observed between both treatment groups nor 14 ± 2 days after the first treatment (p = 0.956) neither regarding the overall cure rate (p = 0.923). In conclusion, the clinical cure of dairy cows' endometritis after the intrauterine application of the herbal product was non-inferior to the intrauterine application of the antibiotic cephapirin. These results could contribute to reduce the antimicrobial use in the daily veterinary routine treatment of endometritis.

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.

Quantitative thermodynamic exposure assessment of PCBs available to sandworms (Alitta virens) in activated carbon remediated sediment during ongoing sediment deposition.

Marine mesoscale studies with sandworms (Alitta virens) were conducted to isolate important processes governing the exposure and bioaccumulation of polychlorinated biphenyls (PCBs) at contaminated sediment sites. Ex situ equilibrium sampling with silicone-coated jars, and in situ passive sampling with low-density polyethylene (LDPE) were used to determine the performance of an activated carbon (AC) amendment remedy applied to the bed sediment. A quantitative thermodynamic exposure assessment ('QTEA') was performed, showing that PCB concentrations in polymers at equilibrium with the surficial sediment were suited to measure and assess the remedy effectiveness with regard to PCB bioaccumulation in worms. In practice, monitoring the performance of sediment remedies should utilize a consistent and predictive form of polymeric sampling of the sediment. The present study found that ex situ equilibrium sampling of the surficial sediment was the most useful for understanding changes in bioaccumulation potential as a result of the applied remedy, during bioturbation and ongoing sediment and contaminant influx processes. The ultrathin silicone coatings of the ex situ sampling provided fast equilibration of PCBs between the sediment interstitial water and the polymer, and the multiple coating thicknesses were applied to confirm equilibrium and the absence of surface sorption artifacts. Overall, ex situ equilibrium sampling of surficial sediment could fit into existing frameworks as a robust and cost-effective tool for contaminated sediment site assessment.

Short-term results of tibial interference screw fixation for transtibial medial meniscus posterior root pull-out repair.

Background: To evaluate the technique of transtibial pull-out repair with tibial interference screw fixation for medial meniscus posterior root (MMPR) tear by reporting on short-term outcomes and complications. Methods: All MMPR repairs performed between January 2019 and August 2021 (n = 70) were retrospectively screened regarding demographic data and surgical parameters. The patients were questioned for performed revision surgery, symptoms and complications. The Numeric Rating Scale (NRS) for pain, Lysholm Knee Score and International Knee Documentation Committee Subjective Knee Form (IKDC) questionnaires were used to evaluate clinical outcome. In cases of revision surgery for re-tear the mode of failure was intraoperatively classified (patients with re-tear were excluded from the clinical follow-up examination). The influence of demographic and treatment parameters (surgical and rehabilitation) on the incidence and mode of re-tear and clinical scores was evaluated. Results: After 2.3 ± 0.7 years, 62 patients (88.6 %) were available for follow-up. There were no direct intra- or postoperative complications. No revision was performed due to symptoms related to the tibial fixation material. The mean surgery time was 33.5 ± 10.8 min. The overall re-tear rate was 17.7 % (11 patients) of whom 10 were treated surgically and one conservatively. Primary mode of failure was suture cut-out from the meniscus (70 %). The NRS, Lysholm Knee Score and subjective IKDC were obtained in 38 patients and improved from 6.8 ± 2.4, 40.1 ± 23.9 and 32.8 ± 16.3 to 2.2 ± 2.2, 80.5 ± 16.3 and 63.0 ± 13.9, respectively (all p < 0.001). No influence was observed from demographic and treatment parameters on re-tear rates or clinical Scores. Conclusions: Tibial interference screw fixation is a fast and promising technique for MMPR transtibial pull-out repair. In the presented technique, utilizing non-absorbable locking sutures alongside tibial interfenrence screw fixation, the primary mode of failure was suture cut-out from the meniscus.

CT-based screening of sarcopenia and its role in cachexia syndrome in pancreatic cancer.

Since computed tomography (CT) is a part of standard diagnostic protocol in pancreatic ductal adenocarcinoma (PDAC), we have evaluated the value of CT for sarcopenia screening in patients with PDAC, intending to expand the diagnostic value of tomographic studies. In our study, we included 177 patients with available CT images. Two groups were formed: Group 1 consisted of 117 patients with PDAC in various locations and stages and Group 2, or the control group, consisted of 60 "nominally healthy" patients with other somatic non-oncological diseases. The body mass index (BMI) was defined as a ratio of patient's weight to the square of their height (kg/m2). CT-based body composition analysis was performed using commercially available software with evaluation of sarcopenia using skeletal muscle index (SMI, cm2/m2). Based on the SMI values, sarcopenia was found in 67.5% of patients (79 out of 117) in the first patient group. It was found more frequently in males (42 out of 56; 75%) than in females (37 out of 61; 60.6%). Additionally, we observed a decrease in muscle mass (hidden sarcopenia) in 79.7% in patients with a normal BMI. Even in overweight patients, sarcopenia was found in 50% (sarcopenic obesity). In patients with reduced BMI sarcopenia was found in all cases (100%). Statistically significant difference of SMI between two groups was revealed for both sexes (p = 0,0001), with no significant difference between groups in BMI. BMI is an inaccurate value for the assessment of body composition as it does not reflect in the details the human body structure. As SMI may correlate with the prognosis, decreased muscle mass- especially "hidden" sarcopenia or sarcopenic obesity- should be reported. The use of CT-based evaluation of sarcopenia and sarcopenic obesity will allow for a better treatment response assessment in patients with cancer cachexia.

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.

Promising Outcomes of Modified ALPPS for Staged Hepatectomy in Cholangiocarcinoma.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a two-stage procedure that can potentially cure patients with large cholangiocarcinoma. The current study evaluates the impact of modifications on the outcomes of ALPPS in patients with cholangiocarcinoma. In this single-center study, a series of 30 consecutive patients with cholangiocarcinoma (22 extrahepatic and 8 intrahepatic) who underwent ALPPS between 2011 and 2021 was evaluated. The ALPPS procedure in our center was modified in 2016 by minimizing the first stage of the surgical procedure through biliary externalization after the first stage, antibiotic administration during the interstage phase, and performing biliary reconstructions during the second stage. The rate of postoperative major morbidity and 90-day mortality, as well as the one- and three-year disease-free and overall survival rates were calculated and compared between patients operated before and after 2016. The ALPPS risk score before the second stage of the procedure was lower in patients who were operated on after 2016 (before 2016: median 6.4; after 2016: median 4.4; p = 0.010). Major morbidity decreased from 42.9% before 2016 to 31.3% after 2016, and the 90-day mortality rate decreased from 35.7% before 2016 to 12.5% after 2016. The three-year survival rate increased from 40.8% before 2016 to 73.4% after 2016. Our modified ALPPS procedure improved perioperative and postoperative outcomes in patients with extrahepatic and intrahepatic cholangiocarcinoma. Minimizing the first step of the ALPPS procedure was key to these improvements.

Are T2WI PI-RADS sub-scores of transition zone prostate lesions biased by DWI information? A multi-reader, single-center study.

PURPOSE: According to PI-RADS v2.1, T2-weighted imaging (T2WI) is the dominant sequence for transition zone (TZ) lesions. This study aimed to assess, whether diffusion-weighted imaging (DWI) information influences the assignment of T2WI scores. METHOD: Out of 283 prostate MRI examinations with correlated biopsy results, fourty-four patients were selected retrospectively: first, 22 patients with a TZ lesion with T2WI and DWI scores ≥ 4, to represent lesions with unequivocal suspicion on T2WI and DWI. Second, 22 additional patients with TZ lesions of similar T2WI appearance but with corresponding DWI score ≤ 3 were added as control. Four residents and one board-certified radiologist each performed two assessments of the included patients: First, only T2WI was available (T2-only read); second, both T2WI and DWI sequences were available (biparametric read). Lesion scores were assessed using Wilcoxon signed-rank test, inter-reader agreement using weighted kappa and Kendall's W statistics, and sensitivity/specificity using McNemar test. RESULTS: The T2WI scores were significantly different between the T2-only and biparametric read for 3 out of 4 residents (p ≤ 0.049) but not for the radiologist. The overall PI-RADS scores derived from the two reading sessions differed considerably for 35/220 cases (all readers pooled). Inter-reader agreement was fair for the T2WI and overall PI-RADS scores (mean kappa 0.27-0.30) and moderate for the DWI scores (mean kappa 0.43). CONCLUSIONS: For inexperienced readers, assessment of T2WI is variable and potentially biased by availability of DWI information, which can lead to changes of overall PI-RADS score and consequently clinical management. Assessment of T2WI should be performed before reviewing DWI to ensure non-biased interpretation of TZ lesions in the dominant sequence.

Effect of Anterior Tibial Closing Wedge Osteotomy on Coronal Tibial Alignment in Relation to Preoperative Medial Proximal Tibial Angle and Wedge Height.

BACKGROUND: The posterior tibial slope has been identified as an anatomic risk factor for anterior cruciate ligament insufficiency and reruptures after anterior cruciate ligament reconstruction. Anterior tibial closing wedge osteotomy for correction of sagittal plane deformities has the potential to cause an unintended change in coronal plane alignment. PURPOSE: To evaluate the effects of anterior tibial closing wedge osteotomies for correction of posterior tibial slope on coronal plane alignment using an infratuberosity surgical approach and to identify predictive factors for a change in medial proximal tibial angle (MPTA). STUDY DESIGN: Case series; Level of evidence, 4. METHODS: This study reports on retrospectively obtained data from radiographic measurements of 38 anterior tibial closing wedge osteotomies. All patients underwent revision anterior cruciate ligament reconstruction and had undergone ≥1 previous anterior cruciate ligament reconstruction. In all patients, an infratuberosity approach was used with angular stable plate fixation. Pre- and postoperative radiographs were examined retrospectively to detect changes in the sagittal and coronal plane alignment (posterior tibial slope and MPTA). A multivariate regression analysis was used to identify predictors for a change in MPTA. RESULTS: The study group consisted of 14 women and 24 men whose mean ± SD age at the index procedure was 31.6 ± 8.7 years (range, 17-51 years). Posterior tibial slope decreased significantly (by 7.2° ± 2.3°; P < .001) from 14.6° ± 2.0° preoperatively to 7.4° ± 2.1° postoperatively. MPTA decreased significantly by 1.3° ± 1.5° (P = .005) from pre- to postoperative measurement. Mean wedge height was 9.3 ± 1.1 mm. A lower preoperative MPTA (coefficient = 0.32; P = .017; 95% CI, 0.06-0.59) and larger wedge height (coefficient = 0.48; P = .029; 95% CI, 0.05-0.9) were significant predictive factors for a decrease in MPTA. CONCLUSION: Anterior tibial closing wedge osteotomy for posterior tibial slope reduction resulted in a slight but significant decrease of the MPTA in the coronal plane. These changes were dependent on the preoperative MPTA and the wedge height.

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.

Pancreatic CT perfusion: quantitative meta-analysis of disease discrimination, protocol development, and effect of CT parameters.

BACKGROUND: This study provides a quantitative meta-analysis of pancreatic CT perfusion studies, investigating choice of study parameters, ability for quantitative discrimination of pancreatic diseases, and influence of acquisition and reconstruction parameters on reported results. METHODS: Based on a PubMed search with key terms 'pancreas' or 'pancreatic,' 'dynamic' or 'perfusion,' and 'computed tomography' or 'CT,' 491 articles published between 1982 and 2020 were screened for inclusion in the study. Inclusion criteria were: reported original data, human subjects, five or more datasets, measurements of pancreas or pancreatic pathologies, and reported quantitative perfusion parameters. Study parameters and reported quantitative measurements were extracted, and heterogeneity of study parameters and trends over time are analyzed. Pooled data were tested with weighted ANOVA and ANCOVA models for differences in perfusion results between normal pancreas, pancreatitis, PDAC (pancreatic ductal adenocarcinoma), and non-PDAC (e.g., neuroendocrine tumors, insulinomas) and based on study parameters. RESULTS: Reported acquisition parameters were heterogeneous, except for contrast agent amount and injection rate. Tube potential and slice thickness decreased, whereas tube current time product and scan coverage increased over time. Blood flow and blood volume showed significant differences between pathologies (both p < 0.001), unlike permeability (p = 0.11). Study parameters showed a significant effect on reported quantitative measurements (p < 0.05). CONCLUSIONS: Significant differences in perfusion measurements between pathologies could be shown for pooled data despite observed heterogeneity in study parameters. Statistical analysis indicates most influential parameters for future optimization and standardization of acquisition protocols. CRITICAL RELEVANCE STATEMENT: Quantitative CT perfusion enables differentiation of pancreatic pathologies despite the heterogeneity of study parameters in current clinical practice.

Evaluation and timing optimization of CT perfusion first pass analysis in comparison to maximum slope model in pancreatic adenocarcinoma.

For implementation, performance evaluation and timing optimization of CT perfusion first pass analysis (FPA) by correlation with maximum slope model (MSM) in pancreatic adenocarcinoma, dynamic CT perfusion acquisitions of 34 time-points were performed in 16 pancreatic adenocarcinoma patients. Regions of interest were marked in both parenchyma and carcinoma. FPA, a low radiation exposure CT perfusion technique, was implemented. Blood flow (BF) perfusion maps were calculated using FPA and MSM. Pearson's correlation between FPA and MSM was calculated at each evaluated time-point to determine optimum timing for FPA. Differences in BF between parenchyma and carcinoma were calculated. Average BF for MSM was 106.8 ± 41.5 ml/100 ml/min in parenchyma and 42.0 ± 24.8 ml/100 ml/min in carcinoma, respectively. For FPA, values ranged from 85.6 ± 37.5 ml/100 ml/min to 117.7 ± 44.5 ml/100 ml/min in parenchyma and from 27.3 ± 18.8 ml/100 ml/min to 39.5 ± 26.6 ml/100 ml/min in carcinoma, depending on acquisition timing. A significant difference (p value < 0.0001) between carcinoma and parenchyma was observed at all acquisition times based on FPA measurements. FPA shows high correlation with MSM (r > 0.90) and 94% reduction in the radiation dose compared to MSM. CT perfusion FPA, where the first scan is obtained after the arterial input function exceeds a threshold of 120 HU, followed by a second scan after 15.5-20.0 s, could be used as a potential imaging biomarker with low radiation exposure for diagnosing and evaluating pancreatic carcinoma in clinical practice, showing high correlation with MSM and the ability to differentiate between parenchyma and carcinoma.

Surgery for intraductal papillary mucinous neoplasms in young patients: High-risk population.

BACKGROUND: Intraductal papillary mucinous neoplasms of the pancreas are uncommon in young individuals. Management of these patients is challenging because the risk of malignancy and recurrence after surgery remains unclear. The aim of the present study was to assess the long-term risk for intraductal papillary mucinous neoplasm recurrence after surgery for intraductal papillary mucinous neoplasms in patients ≤50 years of age. METHODS: Perioperative and long-term follow-up data of patients who had undergone surgery for intraductal papillary mucinous neoplasms between 2004 and 2020 were extracted from a prospective unicentric database and retrospectively analyzed. RESULTS: Seventy-eight patients underwent surgical treatment for benign intraductal papillary mucinous neoplasms (low-grade n = 22 and intermediate-grade n = 21) and malignant intraductal papillary mucinous neoplasms (high-grade n = 16 and intraductal papillary mucinous neoplasm-associated carcinoma n = 19). Severe postoperative morbidity (Clavien-Dindo ≥III) was found in 14 patients (18%). The median length of hospital stay was 10 days. No perioperative mortality was observed. The median length of follow-up was 72 months. Recurrence of intraductal papillary mucinous neoplasm-associated carcinoma was found in 6 patients (19%) with malignant intraductal papillary mucinous neoplasm and 1 patient (3%) with benign intraductal papillary mucinous neoplasm. CONCLUSION: Surgery for intraductal papillary mucinous neoplasm is safe and can be performed with low morbidity and potentially no mortality in young patients. Given the high rate of malignancy (45%), these patients with intraductal papillary mucinous neoplasms represent a high-risk population, and prophylactic surgical treatment should be considered in these patients with long life expectancies. Regular clinical and radiologic follow-up examinations are important to rule out disease recurrence, which is high, especially in patients with intraductal papillary mucinous neoplasm-associated carcinoma.

Evaluation of optimal acquisition delays of DECT iodine maps in pancreatic adenocarcinoma: A potential alternative to the Patlak model of CT perfusion.

Introduction: By using bolus tracking with an appropriate acquisition delay dual-energy computed tomography (DECT) iodine maps might serve as a replacement of CT perfusion maps at reduced radiation exposure. This study aimed to evaluate the optimal acquisition delays of DECT for the replacement of parameter maps calculated with the Patlak model in pancreatic adenocarcinoma by corresponding iodine maps. Materials and methods: Dual-source dynamic DECT acquisitions at 80 kVp/Sn140 kVp of 14 patients with pancreatic carcinoma were used to calculate CT perfusion maps of blood volume and permeability with the Patlak model. DECT iodine maps were generated from individual DECT acquisitions, matching acquisition times relative to prior bolus-triggered three-phase CT acquisitions for investigating different acquisition delays. Correlation between perfusion parameters and iodine concentrations was determined for acquisition delays between -6 s and 33 s. Results: Correlation between iodine concentrations and perfusion parameters ranged from -0.05 to 0.63 for blood volume and from -0.05 to 0.71 for permeability, depending on potential trigger delay. The correlation was significant for potential acquisition delays above 1.5 s for blood volume and above 9.0 s for permeability (both p < 0.05). Maximum correlation occurred at an acquisition delay of 15.0 s for blood volume (r = 0.63) and at 25.5 s for permeability (r = 0.71), with significantly lower iodine concentrations in carcinoma (15.0 s: 1.3 ± 0.5 mg/ml; 22.5 s: 1.4 ± 0.7 mg/ml) than in non-neoplastic pancreatic parenchyma (15.0 s: 2.3 ± 0.8 mg/ml; 22.5 s: 2.4 ± 0.6 mg/ml; p < 0.05). Discussion: In the future, well-timed DECT iodine maps acquired with bolus tracking could provide an alternative to permeability and blood volume maps calculated with the Patlak model.

Technical guidance on biodegradation testing of difficult substances and mixtures in surface water.

The aim of this article is to address critical challenges in the OECD 309 "Aerobic mineralization in surface water - simulation biodegradation test" for volatile chemicals, highly hydrophobic chemicals, mixtures or UVCBs (unknown or variable composition, complex reaction products or biological materials). Several modifications are presented to address technical challenges (minimize and account for losses), make testing more environmentally relevant (lower concentrations) and generate data for multiple substances (more and better aligned data):•Minimizing and accounting for test substance losses: Aqueous solutions are handled using gas tight syringes, tests are conducted in gas tight vials, and automated analysis is performed directly on unopened test vials. Abiotic losses are accounted for via concentration ratios between test systems and abiotic controls that are incubated and measured in parallel.•Testing at low environmentally relevant concentrations: Substances are tested at low concentrations to avoid toxicity and solubility artefacts and analyzed using a sensitive analytical method. Substances are added without co-solvent (using passive dosing) or with a minimum of co-solvent (using microvolume spiking).•Testing of multiple chemicals in mixtures combined with constituent specific analysis: Primary biodegradation kinetics of chemicals are determined in tests of multi-constituent mixtures or UVCBs using constituent specific analysis.

Closed aerobic biodegradation kinetics test with activated sludge and low concentration chemical mixtures.

The activated sludge process at wastewater treatment plants is important to prevent discharge of organic pollutants to the environment. Determination of biodegradation kinetics in activated sludge is challenging for mixtures that cover a diverse range of structures. The aims of this study were to (1) design a closed aerobic biodegradation batch test with activated sludge and (2) develop a sample preparation procedure that is compatible with LC-MS and Solid Phase Microextraction (SPME) coupled to GC-MS. A headspace:sludge ratio of 4:1 was sufficient to ensure aerobic conditions in activated sludge for 7 days at co-solvent concentrations <0.01%. Ethanol was added to sub-samples (50%) to stop biodegradation, extract sorbed chemicals and allow storage at -18 °C without ice formation. The ethanol extracted the chemicals from the sludge before filtration (0.2 µm). The filtrate was diluted in ultrapure water to <12% ethanol before analysis by SPME GC-MS/MS and was suitable for direct injection on LC-MS/MS. Biodegradation was distinguished from sorption through abiotic controls using autoclaved poisoned sludge. Linalool, naphthalene, α-isomethylionone, phenanthrene, citronellol, drometrizole, 2-ethylhexyl 4-methoxycinnamate, dicyclohexyl phthalate, BP-1, BP-3, methyl-, ethyl-, propylparaben, alkyl sulfates and isethionates degraded within 48 h in activated sludge, while musk ketone, tonalide and 1,3,5-trichlorobenzene did not. A 10 times reduction of sludge density did not markedly affect the microbial diversity but slowed biodegradation kinetics (partly explained by theory). This study demonstrated a 'cold' alternative to an OECD 314b test and how biodegradation kinetics can be determined for mixtures of diverse chemicals in closed batch tests with activated sludge.

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.

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.

Alkyl-phenanthrenes in early life stage fish: differential toxicity in Atlantic haddock (Melanogrammus aeglefinus) embryos.

Tricyclic polycyclic aromatic hydrocarbons (PAHs) are believed to be the primary toxic components of crude oil. Such compounds including phenanthrene are known to have direct effects on cardiac tissue, which lead to malformations during organogenesis in early life stage fish. We tested a suite of 13 alkyl-phenanthrenes to compare uptake and developmental toxicity in early life stage haddock (Melanogrammus aeglefinus) embryos during gastrulation/organogenesis beginning at 2 days post fertilization via passive dosing. The alkyl-phenanthrenes were tested at their solubility limits, and three of them also at lower concentrations. Measured body burdens were linearly related to measured water concentrations. All compounds elicited one or more significant morphological defects or functional impairment, such as decreased length, smaller eye area, shorter jaw length, and increased incidence of body axis deformities and eye deformities. The profile of developmental toxicities appeared unrelated to the position of alkyl substitution, and gene expression of cytochrome 1 a (cyp1a) was low regardless of alkylation. Mortality and sublethal effects were observed below the expected range for baseline toxicity, thus indicating excess toxicity. Additionally, PAH concentrations that resulted in toxic effects here were far greater than when measured in whole crude oil exposures that cause toxicity. This work demonstrates that, while these phenanthrenes are toxic to early life stage fish, they cannot individually account for most of the developmental toxicity of crude oil, and that other compounds and/or mixture effects should be given more consideration.