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Different immunohistochemical programmed death-ligand 1 (PD-L1) assays and scorings have been reported to yield variable results in triple-negative breast cancer (TNBC). We compared the analytical concordance and reproducibility of four clinically relevant PD-L1 assays assessing immune cell (IC) score, tumor proportion score (TPS), and combined positive score (CPS) in TNBC. Primary TNBC resection specimens (n = 104) were stained for PD-L1 using VENTANA SP142, VENTANA SP263, DAKO 22C3, and DAKO 28–8. PD-L1 expression was scored according to guidelines on virtual whole slide images by four trained readers. The mean PD-L1 positivity at IC-score ≥1% and CPS ≥1 ranged between 53% and 75% with the highest positivity for SP263 and comparable levels for 22C3, 28–8, and SP142. Inter-assay agreement was good between 28–8 and 22C3 across all scores and cut-offs (kappa 0.68–0.74) and for both assays with SP142 at IC-score ≥1% and CPS ≥1 (kappa 0.61–0.67). The agreement between SP263 and all other assays was substantially lower for all scores. Inter-reader agreement for each assay was good to excellent for IC-score ≥1% (kappa 0.73–0.78) and CPS ≥1 (kappa 0.68–0.74), fair to good for CPS ≥10 (kappa 0.52–0.67) and TPS ≥1% (kappa 0.53–0.72). The percentage of overlapping cases in the positive/negative category was >90% between IC-score ≥1% and CPS ≥1 but below when comparing IC-score ≥1% with CPS ≥10. We demonstrate an overall good inter-reader agreement for all PD-L1 assays in TNBC along with assay specific differences in positivity and concordances, which may aid to select the right test strategy in routine diagnostics. • Different PD-L1 IHC assays and scorings may show variable results in TNBC. • Overall good assay concordance between SP142, 22C3, and 28–8 at IC-score 1%. • Overall good assay concordance between SP142, 22C3, and 28–8 at CPS 1. • SP142 is less optimal for CPS assessment at higher cut-offs. • SP263 assay is not interchangeable with the other three PD-L1 assays. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the safety and efficacy of ticagrelor versus prasugrel for patients with acute coronary syndrome (ACS) according to their estimated glomerular filtration rates (eGFRs). The outcomes of ticagrelor versus prasugrel in patients with ACS according to eGFR have not been defined. Patients (n = 4,012) were categorized into 3 groups: low eGFR (<60 mL/min/1.73 m2), intermediate eGFR (≥60 and <90 mL/min/1.73 m2), and high eGFR (≥90 mL/min/1.73 m2). The primary endpoint was a composite of all-cause death, myocardial infarction, and stroke; the secondary safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding, both at 1 year. Patients with low eGFRs had a higher risk for the primary endpoint compared with patients with intermediate eGFRs (adjusted HR: 1.89; 95% CI: 1.46-2.46]) and those with high eGFRs (adjusted HR: 2.33; 95% CI: 1.57-3.46). A risk excess for low eGFR was also observed for bleeding (adjusted HR: 1.55 [95% CI: 1.12-2.13] vs intermediate eGFR; adjusted HR: 1.59 [95% CI: 1.01-2.50] vs high eGFR). However, eGFR did not affect the relative efficacy and safety of ticagrelor versus prasugrel. In patients with low eGFR, the primary endpoint occurred in 20.5% with ticagrelor and in 14.7% with prasugrel (HR: 1.47; 95% CI: 1.04-2.08; P = 0.029); there was no significant difference in bleeding. These results show that among patients with ACS, reduction of eGFR is associated with increased risk for ischemic and bleeding events but has no significant impact on the relative efficacy and safety of ticagrelor versus prasugrel. (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome [ISAR-REACT 5]; NCT01944800) [Display omitted] [ABSTRACT FROM AUTHOR]

Bone volume changes following vascularized bone flaps and possible confounding factors over time are described in the literature with some controversy. The purpose of this study was to evaluate the bone volume behavior of two frequently used free flaps. Computed tomography (CT) scans were examined with regard to bone volume using the software program ITK-SNAP for all patients who required mandibular reconstruction with a free fibula flap (FFF, conventionally vs assisted by computer-aided design/computer-aided manufacturing (CAD/CAM)) or iliac crest flap (DCIA) following mandibular resection because of benign or malign processes, between August 2010 and August 2015. Clinical data, complication rates, and CT scans were analyzed retrospectively. Additionally, complication rates (microvascular revision, flap loss, postoperative fistula or dehiscence, and postoperative bone exposure) were compared within early (≤30 days), late (31st–100th day), and overall (≤100th day) postoperative time intervals. 113 cases, comprizing 89 FFF and 24 DCIA cases, were included. FFF showed superior bone volume behavior over the DCIA flap. Multivariable regression models assessed the relationships between the following and bone volume behavior: interval between operation and CT scan (p < 0.683), age (p = 0.004), gender (p = 0.006), BMI (p = 0.400), adjuvant radiation therapy (p = 0.334), reconstruction with DCIA flap (p < 0.0001), number of segments (p = 0.02), and incidence of dental implant insertion (p = 0.45). The bone volume of FFFs remains stable. DCIA flaps show a higher bone volume reduction, but the postoperative course might be associated with fewer complications. Time interval between operation and CT scan, age, gender, reconstruction with DCIA flap, and number of fibula segments contributed significantly to bone volume behavior. [ABSTRACT FROM AUTHOR]

Adjuvant chemotherapy decision in patients with hormone receptor positive, HER2 negative breast cancer (BC) is challenging. Ki-67 is widely used for adjuvant therapy decision in BC. The multigene assay EndoPredict (EP) has shown to provide valid and additional information about the risk of recurrence compared to traditional pathological factors. In this study, we compared Ki-67 with EP assay generated risk groups. We analyzed the results from prospective EP testing (n = 373) and tumor proliferation assessed by Ki-67 staining in luminal breast cancer. We statistically investigated the association of both parameters and probed for equivalence in risk stratification. Evaluation of Ki-67 was feasible in 307 (82%) BC specimens with known EP test results. The EPscore (now called 12-gene molecular score) delineated 140 low and 167 high scores. After combining the EPscore with pathological tumor stage and nodal status, we received 203 EPclin low-risk and 104 EPclin high-risk classifications. EPscore and EPclin were significantly associated with Ki-67 indices and tumor grade (p < 0.001). Overall, we observed a moderate correlation between Ki-67 and the EPscore (r = 0.63) as well as the EPclin score (r = 0.59). Ki-67 values above 25% partly overlap with EP test results and therefore indicate a high-risk profile. In these cases, the additional prognostic information from EP testing might be rather low. However, low and intermediate Ki-67 values (less than 25%) alone were not reliable in predicting a low risk EP profile, indicating that EP testing is useful in this subgroup. • Comparison of prospective EndoPredict tests with Ki-67 in a large breast cancer cohort. • EPscore and EPclin were significantly associated with Ki-67 indices. • Ki-67 values above 25% partly overlap with high-risk EP test results. • Ki-67 less than 25% was not reliable in predicting a low-risk EP profile. • EP testing is useful, particularly in breast cancer with low and intermediate Ki-67 levels. [ABSTRACT FROM AUTHOR]

The purpose of the study was to investigate the impact of oral anticoagulation (OAC) type on clinical outcomes 1 year after transcatheter aortic valve replacement (TAVR). Non–vitamin K oral anticoagulants (NOACs) are superior to vitamin K antagonists (VKAs) in nonvalvular atrial fibrillation (AF), while their comparative performance among patients in need of OAC undergoing TAVR is underinvestigated. The study enrolled 962 consecutive patients who underwent TAVR in 4 tertiary European centers and were discharged on either NOACs (n = 326) or VKAs (n = 636). By using propensity scores for inverse probability of treatment weighting (IPTW), the comparison of treatment groups was adjusted to correct for potential confounding. Mean age and Society of Thoracic Surgeons score of the population were 81.3 ± 6.3 years and 4.5% (interquartile range: 3.0% to 7.3%); 52.5% were women and a balloon-expandable valve was used in 62.7% of cases. The primary outcome of interest, combined incidence of all-cause mortality, myocardial infarction, and any cerebrovascular event at 1-year after TAVR, was 21.2% with NOACs versus 15.0% with VKAs (hazard ratio [HR]: 1.44; 95% confidence interval [CI]: 1.00 to 2.07; p = 0.050, IPTW-adjusted). The 1-year incidence of any Bleeding Academic Research Consortium bleeds and all-cause mortality were comparable between the NOAC and VKA groups, 33.9% versus 34.1% (HR: 0.97; 95% CI: 0.74 to 1.26; p = 0.838, IPTW-adjusted) and 16.5% versus 12.2% (HR: 1.36; 95% CI: 0.90 to 2.06; p = 0.136, IPTW-adjusted), respectively. Chronic use of both NOACs and VKAs among patients in need of OAC after TAVR are comparable regarding 1-year bleeding risk. The higher ischemic event rate observed with NOACs needs to be evaluated in large randomized trials. [ABSTRACT FROM AUTHOR]

Venous congestion results in tissue damage and remains the most common failure of free microvascular transfer if it is not recognized early. The purpose of this experimental study was to evaluate venous congestion and describe the findings with two different monitoring tools. A standardized epigastric flap was raised, and total occlusion of the draining vein was temporarily applied for 4, 5, 6, or 7 h. Blood flow measurements, including laser-Doppler flowmetry, and tissue spectrophotometry (O2C) and indocyanine green (ICG) videoangiography using the FLOW ® 800 tool, were performed systematically after each surgical step, an interval of venous occlusion, and 1 week of clinical observation. Both monitoring tools were capable of detecting acute venous occlusion. ICG videoangiography data showed a significant decrease in the first and second maximum, and the area under the curve, during venous occlusion, whereas hemoglobin levels in the O2C analysis remained stable. Changes in fluorescence values in border areas of the flap correlated significantly with the incidence of necrosis. O2C data later showed significant correlation with the area of necrosis, and more individual changes during flap monitoring. ICG videoangiography might therefore be useful in the prediction of flap necrosis in critical areas of perfusion. [ABSTRACT FROM AUTHOR]

Background Women have unfavorable prognosis after myocardial infarction (MI). This text describes sex differences in mortality and in the power of risk predictors in contemporarily-treated MI patients. Methods A population of 4141 MI patients (26.5% females) was followed up for 5 years. Effects of sex and age on total mortality were investigated by multivariable Cox analysis. Mortality predictors were investigated by receiver-operator characteristics analysis. Stepwise multivariable Cox regression was used to create sex-specific predictive models. Results Thirty-day mortality was 1.5-fold higher in women. However, sex was not a significant mortality predictor in a model adjusted for age. Predictors for 5-year mortality performed differently in male and female patients. In women, a sex-specific model provided better risk stratification than a sex-neutral model. Conclusion The unfavorable prognosis of female MI patients can be explained by advanced age. Sex-specific predictive models might improve risk stratification in female survivors of acute MI. [ABSTRACT FROM AUTHOR]

Background We recently reported that nocturnal respiratory rate (NRR) predicts non-sudden cardiac death in survivors of myocardial infarction (MI). Here, we present the details of the technique deriving NRR from ECG recordings. Methods Continuous ECG and respiratory chest excursions were simultaneously recorded in 941 MI survivors who were followed-up for 5-years. Mean respiratory rate was derived from the ECG based on RR intervals, QRS amplitudes, and QRS vectors and compared to chest belt measurements. NRR was calculated from Holter-ECGs accordingly using the same ECG processing. Results Directly-measured and ECG-derived respiratory rates were in good agreement. Areas under the ROC curve for 10-min-ECG- and Holter-derived respiratory rate were well in the confidence intervals of that of the chest belt measurement. The optimum dichotomy of NRR for the prediction of mortality was ≥18.6 breaths per minute. Conclusions The mean respiratory rate can be precisely derived from continuous ECGs. [ABSTRACT FROM AUTHOR]

Successful biomechanical reconstruction is a major goal in total hip arthroplasty (THA). We measured leg length (LL), global (GO) and femoral offset (FO) change on anteroposterior pelvis radiographs and on three-dimensional computed-tomography (3D-CT) with fiducial landmarks after cementless THA on 18 hips of cadaveric specimens. Measurements on radiographs were performed twice by four examiners and showed high interobserver (mean CCC ≥ 0.79) and intraobserver agreements (mean ICC ≥ 0.88). Mean differences between radiographic and 3D-CT measurements were 1.0 (SD 2.0) mm for LL, 0.6 (SD 3.6) mm for GO and 1.4 (SD 5.2) mm for FO. 1% of radiographic LL-, 15% of GO- and 35% of FO measurements were outside a tolerance limit of 5 mm. Radiographs seem acceptable for measuring LL/GO change but fail to reflect FO change in THA. [ABSTRACT FROM AUTHOR]

Purpose: We compared blood pressure (BP) measurements obtained using radial artery applanation tonometry with invasive BP measurements using a catheter placed in the abdominal aorta through the femoral artery in patients with multiple organ dysfunction syndrome (MODS). Materials and Methods: In 23 intensive care unit patients with MODS, we simultaneously assessed BP values for 15 minutes per patient using radial artery applanation tonometry (T-Line TL-200pro device; Tensys Medical Inc, San Diego, Calif) and the arterial catheter (standard-criterion technique). A total of 2879 averaged 10-beat epochs were compared using Bland-Altman plots. Results: The mean difference ± SD (with corresponding 95% limits of agreement) between radial artery applanation tonometry-derived BP and invasively assessed BP was +1.0 ± 5.5 mm Hg (-9.9 to +11.8 mm Hg) for mean arterial pressure, -3.3 ± 11.2 mm Hg (-25.3 to +18.6 mm Hg) for systolic arterial pressure, and +4.9 ± 7.0 mm Hg (-8.8 to +18.6 mm Hg) for diastolic arterial pressure, respectively. Conclusions: In intensive care unit patients with MODS, mean arterial pressure and diastolic arterial pressure can be determined accurately and precisely using radial artery applanation tonometry compared with central aortic values obtained using a catheter placed in the abdominal aorta through the femoral artery. Although systolic arterial pressure could also be derived accurately, wider 95% limits of agreement suggest lower precision for determination of systolic arterial pressure. [ABSTRACT FROM AUTHOR]

Purpose: Accurate prediction of fluid responsiveness is of importance in the treatment of patients admitted to the intensive care unit (ICU). We investigated whether physical examination, central venous pressure (CVP), central venous oxygen saturation (ScvO2), passive leg raising (PLR) test, and transpulmonary thermodilution (TPTD).derived parameters can predict volume responsiveness in patients admitted to the ICU. Materials and Methods: In this prospective study, structured clinical examination, measurement of CVP and ScvO2, a PLR test, and TPTD measurements were performed in 31 patients. A fluid challenge test was performed in 24 patients (fluid responsiveness was defined as a cardiac index [CI] increase of ⩾15%). Results: Physical examination, CVP, ScvO2, the PLR test, and the TPTD-derived volumetric preload parameter global end-diastolic volume index showed poor prognostic capabilities regarding prediction of fluid responsiveness. Twenty-nine percent of patients were fluid responsive. There was a statistically significant correlation between the fluid challenge.induced increase in CI and changes in global enddiastolic volume index (r = 0.666, P b .001). In only 17% of patients, CI did not increase after fluid loading. Conclusions: Prediction of fluid responsiveness is difficult using physical examination, CVP, ScvO2, PLR maneuver, or TPTD-derived variables in critically ill patients. A volume challenge test should be considered for the assessment of fluid responsiveness in critically ill patients admitted to the ICU. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to biomechanically evaluate a new technique of intramedullary cortical button fixation for subpectoral biceps tenodesis and to compare it with the interference screw technique. Methods: We compared intramedullary unicortical button fixation (BicepsButton; Arthrex, Naples, FL) with interference screw fixation (Bio-Tenodesis screw; Arthrex) for subpectoral biceps tenodesis using 10 pairs of human cadaveric shoulders and ovine superficial digital flexor tendons. After computed tomography analysis, the specimens were mounted in a testing machine. Cyclic loading was performed (preload, 5 N; 5 to 70 N at 1.5 Hz for 500 cycles), recording the displacement of the tendon. Load to failure and stiffness were subsequently evaluated with a load-to-failure test (1 mm/s). Results: Cyclic loading showed a displacement of 11.3 ± 2.8 mm for intramedullary cortical button fixation and 9 ± 1.7 mm for interference screw fixation (P = .112). All specimens within the cortical button group passed the cyclic loading test, whereas 3 of 10 specimens within the interference screw group failed by tendon slippage at the screw-tendon-bone interface after a mean of 252 cycles (P = .221). Load-to-failure testing showed a mean load to failure of 218.8 ± 40 N and stiffness of 27.2 ± 7.2 N/mm for the intramedullary cortical button technique. For the interference screw, the mean load to failure was 212.1 ± 28.3 N (P = .625) and stiffness was 40.4 ± 13 N/mm (P = .056). Conclusions: We could not find any major differences in load to failure when comparing the tested techniques for subpectoral biceps tenodesis. Intramedullary cortical button fixation showed no failure during cyclic testing. However, we found a 30% failure rate (3 of 10) for the interference screw fixation. Clinical Relevance: Intramedullary cortical button fixation provides an alternative technique for subpectoral biceps tenodesis with comparable and, during cyclic loading, even superior biomechanical properties to interference screw fixation. [Copyright &y& Elsevier]

Purpose: The aim of this study was to evaluate continuous vancomycin infusion (contV) in intensive care unit patients. Materials and Methods: A retrospective study in 164 patients treated with contV was conducted. They were compared with 75 patients treated with intermittent vancomycin infusion. Results: The median duration of vancomycin therapy in the contV group was 6 (5%-95% percentile range, 2-21) days. The median daily vancomycin dose in the contV group was 960 (526-1723) mg, resulting in a median serum vancomycin plateau concentration of 19.8 (9.8-29.4) mg/L (target: 15-25 mg/L). The contV administration regime was sufficient regarding achievement of the target serum vancomycin concentration. However, in the contV group, serum vancomycin levels were frequently in a subtherapeutic range on treatment days 1 (44%), 2 (29%), and 3 (23%). In the contV group, serum vancomycin concentration determinations per treatment day were performed significantly less often compared with the intermittent vancomycin infusion group (0.38 [0.15-0.75] vs 0.43 [0.22-1.00], P = .041). Conclusions: In medical intensive care unit patients, contV is sufficient to achieve target serum vancomycin concentrations. Because contV frequently resulted in subtherapeutic drug levels on the first days of therapy, a higher loading or starting dose might be necessary. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate prediction factors for extubation failure (need for reintubation within 48 hours) in medical intensive care unit patients. Materials and Methods: Sixty-one patients extubated after mechanical ventilation for more than 48 hours were included in the study. A retrospective analysis of medical records and a prospectively maintained database on respiratory parameters was conducted. Results: Low serum anion gap (P = .001), low serum anion gap corrected for serum albumin (P = .010), and low arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FIO2) ratio (P = .032) were significantly associated with extubation failure. Binary logistic regression analysis revealed low uncorrected and corrected serum anion gap (P = .006 and P = .025, respectively; odds ratio, 0.59 for both) and low PaO2/FIO2 ratio (P = .038; odds ratio, 0.99) as risk factors for extubation failure. Regarding extubation failure, receiver operating characteristic curve (ROC) analysis demonstrated good predictive capabilities of serum anion gap (ROC area under the curve, 0.835; P = .004; cutoff, 7.7 mEq/L; sensitivity, 70.4%; specificity, 85.7%) and corrected serum anion gap (ROC area under the curve, 0.808; P = .009; cutoff, 8.8 mEq/L; sensitivity, 87.5%; specificity, 71.4%). A significantly higher risk for extubation failure was observed in patients with serum anion gap 5.2 mEq/L or less (relative risk, 8.8; 95% confidence interval, 2.4-32.4; P = .004) and corrected serum anion gap 8.6 mEq/L or less (relative risk, 10.0; 95% confidence interval, 2.2-44.9; P = .004). Conclusions: Low preextubation serum anion gap values and low preextubation PaO2/FIO2 ratio might help to predict extubation failure in medical intensive care unit patients. [ABSTRACT FROM AUTHOR]

Background: Patients aged 80 years and older who require cardiac surgical procedures are an increasing population and usually present with considerable comorbidity. Detailed operative risk stratification versus long-term survival and quality of life after surgery is mandatory. Methods: A retrospective analysis was performed on 1,003 patients aged 82.3 years (range, 80 to 94 years) who underwent aortic valve replacement (n = 303), coronary artery bypass grafting (n = 403), or aortic valve replacement with coronary artery bypass grafting (n = 297) between 1987 and 2006. Preoperative data, operative outcome, long-term survival, and predictors for early and late mortality were analyzed. Furthermore, the Short Form 36 Health Status questionnaire was used to evaluate the quality of life. Results: Overall in-hospital mortality was 7.1%. Overall actuarial survival at 1, 5, and 10 years was 81.6% ± 1.2%, 60.4% ± 1.9%, and 23.3% ± 2.6% (mean survival time, 6.25 ± 0.2 years) and showed no significant difference compared with an age- and sex-matched general population. Multivariate analysis showed that preoperative creatinine concentration greater than 1.3 mg/dL (p < 0.001), preoperative atrial fibrillation (p < 0.005), and postoperative prolonged ventilation (p < 0.001) were independent predictors for poor long-term survival. The physical health summarized score of the Short Form 36 Health Status questionnaire was significantly increased in the study population compared with a German standard population aged 80 years and older (p < 0.05). Conclusions: Despite an increased operative mortality, octogenarians showed a considerable quality of life and an excellent long-term survival. To further improve surgical outcome in octogenarians, patient selection should be done with consideration of the identified independent preoperative risk factors. [ABSTRACT FROM AUTHOR]

The aims of our study were to determine first circadian influences on central concentrations of the neuropeptides oxytocin and arginine-vasopressin and second to investigate if these central concentrations are associated with those in the peripheral compartments blood and saliva in neurocritical care patients. We therefore included patients with external ventricular drain who attended a neurosurgical intensive care unit and were not exposed to painful or stressful stimuli during the sampling period. For this purpose, blood, cerebrospinal fluid and saliva were collected in a 24-hour-interval at the timepoints 06:00, 12:00, 18:00 and 24:00. In none of the three body fluids examined, significant time-dependent fluctuations of oxytocin and arginine-vasopressin concentrations could be detected during the 24-hour sampling period. The only exception was the subgroup of postmenopausal women whose oxytocin concentrations in cerebrospinal fluid at 12:00 were significantly higher than at 18:00. Correlations of blood and cerebrospinal fluid and blood and saliva neuropeptide levels were very weak to weak at each timepoint. Cerebrospinal fluid and saliva oxytocin levels showed a moderate correlation at 06:00 but did correlate very weak at the other timepoints. Central as well as peripheral oxytocin and arginine-vasopressin concentrations in neurocritical care patients did not show significant diurnal fluctuations. No strong correlations between central and peripheral neuropeptide concentrations could be detected under basal conditions. If investigators even though decide to use saliva concentrations as surrogate parameter for central neuropeptide activity, they have to consider that correlations of cerebrospinal fluid and saliva oxytocin seem to be highest in the early morning. • Diurnal variations of central neuropeptide concentrations have been described in several species including humans • We could not show circadian rhythmicity of central OXT and AVP levels in neurocritical care patients under basal conditions • No strong correlations between central and peripheral neuropeptide concentrations could be detected • Correlations of oxytocin CSF and saliva levels may depend on the timepoint of sampling [ABSTRACT FROM AUTHOR]

Objective: Ward rounds are an essential part of physicians' daily routine. Existing studies suggest that their practical implementation is inconsistent. Therefore, developing interventions to train ward round competence and assessing if they are effective educational tools are crucial goals for research.Methods: We analysed a simulation-based tutorial dedicated to fourth-year medical students, including casework and ward round simulation. We investigated the effectiveness of this intervention regarding ward round competence through a randomized controlled trial. Performance was assessed with the modified/validated surgical ward round assessment tool by two blinded and trained raters. Supplementary, motivation during the ward round tutorial was assessed for all students at different time points.Results: Analysis of the ratings show that, in contrast to the control group (pre: 66.1 vs. post: 64.8 points, p =  0.72), the ward round competence of the intervention group (pre: 62.6 vs. post: 69.6 points, p =  0.0169) improved significantly after participating in the ward round tutorial.Conclusion: The results show that our simulation-based training is an effective way to improve competence of medical students in conducting surgical ward rounds.Practice Implications: Participation in ward round trainings is a valuable tool to prepare students for their future professional practise. [ABSTRACT FROM AUTHOR]

Blood pressure drops during endovascular treatment of acute ischemic stroke have been associated with worse outcomes for stroke patients. We aimed to evaluate this observation in our patient population. Retrospective study. University hospital. Records from patients who underwent endovascular treatment of acute ischaemic stroke under general anaesthesia at a university hospital from 2017 to 2020 were screened. 586 patients aged 78 years (interquartile range [IQR] 67–84) with a mean National Institutes of Health Stroke Scale score of 15 (IQR 8–19) were included. None. Good functional outcome was defined as a three-month modified Rankin Scale (mRS) value between 0 and 2, or a mRS value less than or equal to the pre-stroke baseline. In addition to well-established predictors, blood pressure before reperfusion was found to be associated with good functional outcomes. Per five minutes that systolic arterial pressure spent below 140 mmHg, the odds of good outcome decreased by 11.1 %. In this retrospective study of general anaesthesia for endovascular stroke therapy, blood pressure drops during the intervention were associated with reduced odds of a good functional outcome three months later. Before a clinical recommendation can be made, a prospective study must clarify effective and safe target ranges of blood pressure support and augmentation. • Anaesthesiologists can enhance the success of endovascular stroke thrombectomy. • A number of patient and procedure characteristics are associated with outcome. • The duration and magnitude of blood pressure drops correlate with worse outcome. [ABSTRACT FROM AUTHOR]

Background: Whether the access site influences the comparative efficacy and safety of ticagrelor and prasugrel in patients with acute coronary syndrome (ACS) undergoing invasive treatment strategy remains unstudied.Methods: This post-hoc analysis included ACS patients undergoing invasive treatment via radial or femoral access and randomized to either ticagrelor or prasugrel in the ISAR-REACT 5 trial. The primary efficacy endpoint was the composite of death, myocardial infarction (MI) or stroke, safety endpoint was BARC 3 to 5 bleeding. Outcomes were assessed out to 12 months after randomization.Results: Out of 4018 patients, 3984 underwent invasive treatment via radial or femoral access. 1479 had coronary angiography via radial access (ticagrelor, N = 748; prasugrel, N = 731) and 2505 via femoral access (ticagrelor, N = 1245; prasugrel, N = 1260). There was no interaction between access route and assignment to either ticagrelor or prasugrel regarding the primary efficacy or safety endpoints (P for interaction≥0.616). In the radial group, the primary efficacy endpoint (7.6% versus 5.8%, HR: 1.32 [0.88-1.97], P = 0.151) and the safety endpoint (4.3% versus 3.0%, HR: 1.36, [0.73-1.31], P = 0.300) were not statistically different in patients receiving either ticagrelor or prasugrel. In the femoral group, the primary efficacy endpoint occurred more frequently in patients assigned to ticagrelor as compared to prasugrel (10.3% versus 7.3%, HR: 1.44 [1.10-1.88], P = 0.006) without significant difference in terms of safety endpoint (6.4% versus 5.8%, HR: 1.14, [0.81-1.60], P = 0.470).Conclusions: In patients with ACS undergoing an invasive treatment strategy, the access route does not influence the comparative efficacy and safety of ticagrelor and prasugrel.Clinical Trial Registration: NCT01944800. [ABSTRACT FROM AUTHOR]

Background: Current guidelines recommend intensified platelet inhibition by prasugrel or ticagrelor in patients with unstable angina (UA) or non-ST-segment elevation (NSTE) myocardial infarction (MI).Objectives: This study sought to investigate the benefits and risks of ticagrelor as compared with prasugrel in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) and planned invasive management.Methods: This post hoc analysis combines the pre-specified subgroups of UA and NSTEMI of the randomized ISAR-REACT 5 trial. It included 1,179 patients assigned to ticagrelor and 1,186 assigned to prasugrel. Ticagrelor was started immediately after randomization and prasugrel after coronary angiography. The primary endpoint was a composite of death, MI, or stroke during 1-year follow-up, and the safety endpoint was Bleeding Academic Research Consortium class 3-5.Results: The primary endpoint was reached in 101 (8.7%) patients in the ticagrelor and in 73 (6.3%) patients in the prasugrel group (hazard ratio [HR]: 1.41; 95% confidence interval [CI]: 1.04 to 1.90). The HR for all-cause death was 1.43 (95% CI: 0.93 to 2.21) and that for MI 1.43 (95% CI: 0.94 to 2.19). The safety endpoint occurred in 49 (5.2%) patients in the ticagrelor and in 41 (4.7%) patients in the prasugrel group (HR: 1.09; 95% CI: 0.72 to 1.65). Landmark analysis revealed persistence of the efficacy advantage with prasugrel after the first month.Conclusions: In patients with NSTE-ACS, we found that prasugrel was superior to ticagrelor in reducing the combined 1-year risk of death, MI, and stroke without increasing the risk of bleeding. Due to the post hoc nature of the analysis, these findings need confirmation by further studies. (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome; NCT01944800). [ABSTRACT FROM AUTHOR]

Objectives To assess the ability of multislice detector computed tomography (MDCT) to differentiate old versus acute/subacute vertebral fractures (VF) and to identify characteristic MDCT imaging signs. Methods 74 consecutive patients demonstrated 192 VF that were classified as either acute/subacute or old based on magnetic resonance imaging, MDCT, and clinical information as reference standard. Classification as acute/subacute versus old fractures based on MDCT alone was evaluated on a Likert scale by 2 independent radiologists. Morphologic MDCT features of fractures, such as trabecular compaction or fracture line, were recorded. Receiver operating characteristic analyses and Cohen's κ were used to assess the discriminatory power of the MDCT and interrater agreement, respectively. Results Out of all 192 VF, 148 fractures were acute/subacute and 44 were old according to the reference standard. Receiver operating characteristic analyses of sole MDCT assessment showed very good identification of acute/subacute VF, with areas under the curve of 0.854 and 0.861 for readers 1 and 2, respectively. When indeterminate findings were treated as acute/subacute fractures, sensitivity and specificity were 97.2% and 58.1% for reader 1 and 94.5% and 65.1% for reader 2. Interrater agreement regarding fracture age was good (weighted Cohen's κ = 0.607). Trabecular compression/callus distinct from the cortex (double compaction sign) was present in approximately half of acute/subacute VF and highly specific for acute/subacute VF (specificity = 93.2% and 88.6% for readers 1 and 2, respectively). Conclusion The acuity of VF can be assessed by MDCT alone with high sensitivity and in case of a double compaction sign with high specificity. [ABSTRACT FROM AUTHOR]

Background Magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI), is an excellent tool for diagnosing intracranial infection, with limitations in previous neurosurgical intervention. This study aimed to evaluate the accuracy of DWI in the diagnosis of postoperative intracranial infection. Methods We retrospectively evaluated all consecutive patients with intracranial infection undergoing a neurosurgical intervention who had preoperative MRI, including DWI. Patients were divided into 2 groups: spontaneous intracranial infection (SI) and postoperative intracranial infection (PI). A control group (CG) of patients who had undergone brain surgery without any signs of subsequent infection was also included. Qualitatively, MRI data were evaluated for the presence of intracranial infection. Sensitivity, specificity, and positive and negative predictive values for PI as opposed to no infection were determined. Quantitatively, areas with diffusion restriction within the surgery/abscess cavity were identified for the 3 groups using semiautomated segmentation. Group differences regarding apparent diffusion coefficient (ADC) ratios were evaluated. Receiver operating characteristic curve analysis was used to identify a point in time beyond which ADC ratios might show reasonable discriminatory power between the PI and CG groups. Results A total of 78 patients were included (38 in the SI group, 20 in the PI group, 20 in the CG group). Sensitivity, specificity, and positive and negative predictive values in the diagnosis of PI were 80%, 95%, 4%, and 100%, respectively. Median ADC was significantly higher in the PI group compared with the SI group (0.98 vs. 0.69; P < 0.001) but lower compared with the CG group (1.24; P = 0.16). The analysis suggested a possible differentiation of PI and CG after a time interval of approximately 100 days/3 months. Conclusions DWI is of limited value in evaluating postoperative brain infection. Our data show a trend toward DWI regaining its validity at approximately 3 months after surgery. Highlights • Diffusion-weighted imaging (DWI) is useful for the diagnosis of intracranial infection. • Interpretation of DWI becomes challenging in a postoperative setting. • The validity of DWI for infection is dependent on the time to preceding surgery. [ABSTRACT FROM AUTHOR]

Post-COVID syndrome (PCS) is defined by symptom persistence accompanied by daily life impairment (DLI). The association of somatic symptom disorder (SSD) and symptoms with DLI after SARS-CoV-2 infection in the general population is unclear to date. The main objective of the study was to investigate the association of possible SSD, depression, anxiety, and participant-reported symptoms with DLI in a local population sample. Anonymised cross-sectional study. A symptom questionnaire, including the scales Patient Health Questionnaire PHQ-15 (somatisation module), SSD-12 (psychological distress in SSD), PHQ-2 (depression), GAD-2 (anxiety), and FAS (fatigue assessment scale) was sent in 02/2022 to all adult residents of the district Bad Tölz-Wolfratshausen, Germany, who were registered for SARS-CoV-2-infection between 03/2020 and 11/2021 (8925 delivered). Associations between DLI, symptoms and scales were estimated using binary logistic regression models and network analysis. 2828 questionnaires (31.7%) were complete. 1486 (52.5%) reported persistent symptoms, and 509 (18.0%) perceived DLI. DLI was strongest associated with self-reported fatigue (OR 7.86; 95%CI 5.63–10.97), dyspnea (3.93; 2.73–5.67), impaired concentration (3.05; 2.17–4.30), SSD-12 (4.36; 2.57–7.41), and PHQ-2 (2.48; 1.57–3.92). Self-reported fatigue showed the strongest correlation (r p = 0.248) and closest proximity to DLI in network analysis. PCS appears as a complex clinical picture in which SSD might play an important role when DLI is present. The pychological burden might partly be explained by the persistent symptoms, which are difficult to treat up to now. Screening for SSD could help in differential diagnostic decision-making to ensure that patients receive appropriate psychosocial interventions for disease coping. • 18% suffered from daily life impairment (DLI) after SARS-CoV2 infection. • 52% had long lasting symptoms more than three months after infection. • DLI was mainly associated with fatigue and somatic symptom disorder (SSD-12). • 25% of participants with DLI suffered from SSD. • Psychological burden might partly be explained by complex and persistent symptoms. [ABSTRACT FROM AUTHOR]

Study Objective: Postinduction and intraoperative hypotension are associated with organ injury in non-cardiac surgery patients. Automated ambulatory blood pressure monitoring can identify chronic arterial hypertension and nocturnal blood pressure non-dipping. We tested the hypotheses that: a) chronic arterial hypertension and nocturnal non-dipping are independent risk factors for postinduction and intraoperative hypotension; and b) adding information on chronic arterial hypertension and nocturnal non-dipping improves hypotension prediction models based on readily available preoperative clinical information.Design: Prediction model development based on a secondary analysis of a prospective observational study.Setting: German university medical center.Patients: 366 non-cardiac surgery patients who had preoperative automated ambulatory blood pressure monitoring.Measurements: Multivariable analyses to identify risk factors for postinduction and intraoperative hypotension. Area under receiver operating characteristics curves (AUROC) and likelihood-ratio tests to test whether adding information on chronic arterial hypertension and nocturnal non-dipping improves hypotension prediction models based on readily available preoperative clinical information.Main Results: Risk factors for postinduction hypotension were age in years (odds ratio: 1.06 (95% confidence interval: 1.03 to 1.10), P = 0.001), American Society of Anesthesiologists physical status class (1.85 (1.02 to 3.35), P = 0.043), preoperative use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (15.19 (1.76 to 131.46), P = 0.013), chronic arterial hypertension (2.54 (1.49 to 4.34), P = 0.001), and nocturnal non-dipping (3.61 (2.09 to 6.23), P < 0.001). The model's AUROC was 0.76 (95% confidence interval: 0.71 to 0.81) with and 0.67 (0.62 to 0.73) without information on chronic arterial hypertension and nocturnal non-dipping (P < 0.001). Risk factors for intraoperative hypotension were male sex (1.73 (1.07 to 2.80), P = 0.025), chronic arterial hypertension (4.35 (2.33 to 8.14), P < 0.001), and nocturnal non-dipping (3.56 (2.07 to 6.11), P < 0.001). The model's AUROC was 0.76 (0.70 to 0.81) with and 0.63 (0.57 to 0.69) without information on chronic arterial hypertension and nocturnal non-dipping (P < 0.001).Conclusions: Chronic arterial hypertension and nocturnal non-dipping are independent risk factors for postinduction and intraoperative hypotension in non-cardiac surgery patients. Adding information on chronic arterial hypertension and nocturnal non-dipping moderately improved hypotension prediction models based on preoperative clinical information. [ABSTRACT FROM AUTHOR]

Abstract: Bisphosphonate related osteonecrosis of the jaw (BRONJ) is rare but potentially severe, and the etiopathology and risk factors are poorly defined. To date, it has not been possible to induce BRONJ in a large animal model, a shortfall this study aims to redress. Ten two-year-old adult Göttingen minipigs were split into two groups. Five pigs (group 1) were administered intravenously a weekly dose of a bisphosphonate (zoledonate 0.05mg/kg body weight, approximating the oncologic dose in humans) and five pigs (group 2) served as controls. After 6weeks, tooth extractions were performed in the upper and lower jaw (both groups) and the bisphosphonate administration continued for a further 10weeks (group 1 only). Clinical and blood parameters were monitored throughout the entire experiment; thereafter, the jaw-bones were subjected to macroscopic, radiological (CT) and histological investigations. Whilst the extraction sites in the control group healed within two weeks, all animals in the bisphosphonate group exhibited exposed bone and impaired wound healing, indicators that are synonymous of macroscopically advanced osteonecrosis. Radiological and in particular histological investigations confirmed the presence of BRONJ in the animals from group 1. This paper demonstrates that the administration of bisphosphonates, in combination with tooth extractions, induces BRONJ in a minipig model. The ability to study BRONJ in miniature pigs, animals with a bone structure not dissimilar to humans, may improve our knowledgebase regarding the etiopathology, the prophylaxis and potentially uncover new therapies of BRONJ. [Copyright &y& Elsevier]

Abstract: Purpose: DNA methylation contributes to carcinogenesis by mediating transcriptional regulation and chromatin remodelling, which may influence the effect of DNA-damaging drugs. We examined the prognostic and predictive impact of DNA methyltransferase (DNMT) 1 and 3b expression in gastric carcinomas (GC) treated by neoadjuvant chemotherapy. In vitro, DNMT1 expression and chemosensitivity were investigated for a functional relationship and the DNMT inhibitor decitabine (DAC) was tested as an alternative treatment option. Patients and methods: DNMT1/3b expression was analysed immunohistochemically in 127 pretherapeutic biopsies of neoadjuvant (platinum/5-fluorouracil)-treated GC patients and correlated with response and overall survival (OS). Short hairpin RNA technology was used to knockdown DNMT1 in the GC cell line, AGS. The chemosensitivity of GC cell lines to DAC alone and to DAC in combination with cisplatin was analysed by XTT or colony formation assays. Results: High DNMT1 and DNMT3b expression was found in 105/127 (83%) and 79/127 (62%) carcinomas, respectively. Patients with low DNMT1 expression demonstrated a significantly better histopathological/clinical response (P =0.03/P =0.008) and OS (P log-rank =0.001). In vitro, knockdown of DNMT1 caused an increased chemosensitivity towards cisplatin. Combined treatment with cisplatin and DAC showed a synergistic effect leading to increased cytotoxicity in the cisplatin-resistant cell line AGS. Conclusion: Low DNMT1 expression defines a subgroup of GC patients with better outcomes following platinum/5FU-based neoadjuvant chemotherapy. In vitro data support a functional relationship between DNMT1 and cisplatin sensitivity. Besides its potential use as a predictive biomarker, DNMT1 may represent a promising target for alternative therapeutic strategies for a subset of GC patients. [Copyright &y& Elsevier]

Abstract: Purpose: We evaluated DNA polymorphisms in genes related to DNA repair, cell-cycle control and tumour microenvironment to determine possible associations with response and survival in neoadjuvant-treated gastric cancer patients. Patients and methods: One hundred and seventy eight patients who received platinum/5FU-based chemotherapy were genotyped for 10 polymorphisms in nine genes (ERCC1: Asn118Asn, C > T; ERCC1: 8092C>A; TP53: Arg72Pro, G A; STK15: Phe31Ile, A > T; VEGF: 936C > T; TNF-α: -308G > A; interleukin-1b (IL-1B): -511C > T; IL-1 receptor antagonist (IL-1RN): variable tandem repeat; IL-8: -251T > A). Genotypes were correlated with histopathological and clinical response and overall (OS) and progression-free survival (PFS). Results: Only the cyclinD1 genotypes were associated with clinical response (). Significantly worse survival rates were noted in patients homozygous for the G-allele as compared to patients with the AG or AA genotypes of the cyclinD1 polymorphism (OS: Plog-rank =0.024; PFS: Plog-rank =0.007) and in patients homozygous for the short allele compared to all other genotypes at the IL-1RN polymorphic locus (OS: Plog-rank =0.026; PFS: Plog-rank =0.013). The combination of both unfavourable genotypes demonstrated strong prognostic relevance (OS: Plog-rank =0.006; PFS: Plog-rank =0.001). Multivariate analysis for OS in the group of completely resected patients (n =139) revealed statistical significance for ypM (P <0.001), histopathological response (P <0.001) and the combined cyclinD1/IL-1RN genotypes (P =0.043). Conclusion: The cyclinD1 and IL-1RN polymorphisms were associated with survival. The combination of specific cyclinD1 and IL-1RN genotypes showed a particular prognostic relevance and should be considered an independent prognostic marker for neoadjuvant-treated gastric cancer patients. [Copyright &y& Elsevier]