Propensity matched comparison of TAVI and SAVR in intermediate-risk patients with severe aortic stenosis and moderate-to-severe chronic kidney disease: a subgroup analysis from the German Aortic Valve Registry.

OBJECTIVE: We compared TAVI vs. SAVR in patients with moderate-to-severe chronic kidney disease (eGFR 15-60 ml/min/1.73 m2) for whom both procedures could possibly be considered (age ≤ 80 years, STS-score 4-8). BACKGROUND: According to both ACC/AHA and ESC/EACTS recent guidelines, aortic stenosis may be treated with either transcatheter (TAVI) or surgical (SAVR) aortic valve replacement in a subgroup of patients. A shared therapeutic decision is made by a heart team based on individual factors, including chronic kidney disease (CKD). METHODS: Data from the large nationwide German Aortic Valve Registry were used. A propensity score method was used to select 704 TAVI and 374 SAVR matched patients. Primary endpoint was 1-year survival. Secondary endpoints were clinical complications, including pacemaker implantation, vascular complications, myocardial infarction, bleeding, and the need for new-onset dialysis. RESULTS: One-year survival was similar (HR [95% CI] for TAVI 1.271 [0.795, 2.031], p = 0.316), with no divergence in Kaplan-Meier curves. In spite of post-procedural short-term survival being numerically higher for TAVI patients and 1-year survival being numerically higher for SAVR patients, such differences did not reach statistical significance (96.4% vs. 94.2%, p = 0.199, and 86.2% vs. 81.2%, p = 0.316, respectively). In weighted analyses, pacemaker implantation, vascular complications, and were significantly more common with TAVI; whereas myocardial infarction, bleeding requiring transfusion, and longer ICU-stay and overall hospitalization were higher with SAVR. Temporary dialysis was more common with SAVR (p < 0.0001); however, a probable need for chronic dialysis was rare and similar in both groups. CONCLUSION: Both TAVI and SAVR led to comparable and excellent results in patients with moderate-to-severe CKD in an intermediate-risk population of patients with symptomatic severe aortic stenosis for whom both therapies could possibly be considered.

Impact of chronic kidney disease in 29 893 patients undergoing transcatheter or surgical aortic valve replacement from the German Aortic Valve Registry.

OBJECTIVES: Chronic kidney disease (CKD) is a key risk factor in patients undergoing transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR). We analysed the impact of estimated glomerular filtration rate (eGFR) and CKD stages on their mid-term survival. METHODS: Data from 29 893 patients enrolled in the German Aortic Valve registry from January 2011 to December 2015 receiving TAVI (n = 12 834) or SAVR (n = 17 059) at 88 sites were included. The impact of renal impairment, as measured by eGFR and CKD stages, was investigated. The primary end-point was 1-year cumulative all-cause mortality. RESULTS: Higher CKD stages were significantly associated to lower in-hospital, 30-day- and 1-year survival rates. Both TAVI- and SAVR-treated patients in CKD 3a, 3b, 4 and 5 stages showed significant and gradually increasing HR values for 1-year all-cause mortality. The same trend persisted in multivariable analysis, although HR values for CKD 3a and 5 did not reach significance in TAVI patients, whereas CKD 4 + 5 did not reach statistical significance in SAVR. Likewise, eGFR as a continuous variable was a significant predictor for 1-year mortality, with the best cut-off points being 47.4 ml/min/1.73 m2 for TAVI and 59.8 ml/min/1.73 m2 for SAVR. Significant 8.6% and 9.0% increases in 1-year mortality were observed for every 5-ml reduction in eGFR for TAVI and SAVR, respectively. CONCLUSIONS: CKD ≥3b and CKD ≥3a are the independent major risk factors for mortality in patients undergoing TAVI and SAVR, respectively. In the overall population of patients with severe aortic stenosis, an appropriate stratification based on CKD substage may contribute to a better selection of patients suitable for such therapies.

Transcatheter or surgical aortic valve implantation in chronic dialysis patients: a German Aortic Valve Registry analysis.

OBJECTIVES: The aim of this study was to compare outcomes of transcatheter and surgical aortic valve implantation in chronic dialysis patients with aortic valve stenosis (AS). BACKGROUND: Chronic dialysis patients undergoing heart valve surgery are at higher risk for morbidity and mortality. Whether interventional techniques can reduce this risk is unclear because dialysis patients have thus far been excluded from randomized trials. METHODS: Chronic dialysis patients with AS enrolled in the German Aortic Valve Registry (GARY) between 2012 and 2015 were analyzed to compare transcatheter aortic valve implantation (TAVI n = 661) with surgical aortic valve replacement (SAVR n = 457). Propensity scores for inverse probability of treatment weighting (IPTW) were used to adjust the comparison of the two treatment groups for potential confounders. RESULTS: TAVI patients were older (78 ± 7.3 vs. 69 ± 10.2 years, p < 0.01, unadjusted) and had more comorbidities. Mortality at 1 year was the same (TAVI: 33.4% vs. SAVR 35.0%, p = 0.72, IPTW-adjusted) while it was lower with TAVI at 30 days (8.6% vs. 15.0%, p = 0.02, IPTW-adjusted). TAVI patients required more pacemaker implantation and showed more aortic regurgitation. SAVR patients required more blood transfusions and had longer hospital stay. Diabetes mellitus, atrial fibrillation, previous PCI, urgent procedure and EuroSCORE were associated with elevated 30-day mortality. Atrial fibrillation and older age were independent risk factor of 1-year mortality in both groups. CONCLUSIONS: Chronic dialysis patients with AS undergoing TAVI or SAVR had the same 1-year mortality, although survival at 30 days was better with TAVI. These results suggest that TAVI may improve peri-procedural outcomes.

Propensity-Matched Comparison of Two Different Access Modes for Minimally Invasive Mitral Valve Surgery.

Mitral valve surgery is being performed routinely using minimally invasive operative techniques. We aimed comparing perioperative and long-term outcomes of minimally invasive mitral valve surgery using 2 different surgical approaches, partial upper sternotomy (PUS) vs right anterolateral minithoracotomy (RAT). From January 1998 through December 2015, 1006 patients underwent mitral valve surgery using a minimally invasive access in our institution. Logistic regression analysis was used to identify covariates among 18 patient variables including the type of mitral valve surgery. Using the significant regression coefficients, each patient's propensity score was calculated, allowing selectively matched subgroups of 243 patients each. Results are based on the matched cohorts between the 2 groups. The PUS approach was performed by 8 surgeons whereas the RAT approach by 2. PUS led to slightly longer duration of the cross-clamp time (100 ± 28 vs 88 ± 26 minutes, P < 0.001) whereas ventilation time (9 ± 37 vs 11 ± 66 hours, P < 0.001) was shorter in PUS than in RAT group. Besides the number of pacemaker implants (PUS: 6.6% vs RAT: 0.4, P = 0.0005) and postoperative chest tube drainage amount at 24 hours (PUS: 556 ± 557 mL/24 h vs RAT: 716 ± 580 mL/24 h, P < 0.001) no differences between the 2 groups regarding further perioperative outcome were observed. Long-term survival and freedom from mitral valve reintervention were comparable between the 2 groups at 6- and 8 years' follow-up. Minimally invasive mitral valve surgery can be performed safely using a PUS or RAT approach without any differences regarding perioperative and long-term morbidity and mortality. Although the RAT approach may be cosmetically more appealing in female patients, PUS may facilitate both safe performance of mitral valve surgery and resident training.

Quinolone and Multidrug Resistance Predicts Failure of Antibiotic Prophylaxis of Spontaneous Bacterial Peritonitis.

BACKGROUND: The efficacy of antibiotic prophylaxis to prevent spontaneous bacterial peritonitis (SBP) in patients colonized with multidrug-resistant organisms (MDROs) is unknown. We evaluated the effectiveness of fluoroquinolone-based SBP prophylaxis in an era and area of frequent antibiotic resistance. METHODS: This is a prospective observational study in patients with liver cirrhosis and an indication for fluoroquinolone-based prophylaxis of SBP. Patients were recruited and followed in a large German tertiary reference center with comprehensive microbiological and clinical monitoring performed at baseline and after 30, 60, 90, and 180 days of prophylaxis. RESULTS: Overall, 77 patients received antibiotic prophylaxis for an average of 93 days. Baseline prevalence of colonization with MDROs was high (N = 39, 50.6%). At least one de novo MDRO was detected in 27 patients (35.1%) during antibiotic prophylaxis; 33 patients (42.9%) developed secondary infections, including 14 cases (17.9%) of infections with MDROs, and 13 cases (16.9%) of de novo/recurrent SBP. Thirty patients (39.0%) died during follow-up. Significantly higher risks of SBP development during antibiotic prophylaxis were observed for patients with versus without any apparent MDROs (P = .009), vancomycin-resistant enterococci (P = .008), multidrug-resistant gram-negative bacteria (P = .016), or quinolone-resistant gram-negative bacteria (QR-GNB) (P = .015). In competing risk analysis, QR-GNB were independently associated with prophylaxis failure (hazard ratio, 3.39; P = .045) and infections with QR-GNB were independently associated with death before SBP (subdistribution hazard risk, 6.47; P = .034). CONCLUSIONS: Antibiotic prophylaxis of SBP appears to be less efficient in patients with known MDROs. Regular MDRO screening seems to be useful to tailor treatment of secondary infections and re-evaluate antibiotic prophylaxis in case of selection of quinolone resistance.

Image-guided interstitial high-dose-rate brachytherapy for dose escalation in the radiotherapy treatment of locally advanced lung cancer: A single-institute experience.

PURPOSE: To evaluate the clinical outcome after CT-guided interstitial high-dose-rate (HDR) brachytherapy for dose escalation in the radiotherapy treatment of inoperable locally advanced non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: From 2005 to 2015, 16 patients with unresectable NSCLC were treated. Median age was 65.7 years (range, 52-86). The median tumor volume was 95.3 cm3 (range, 20.0-2000.0). The median prescribed HDR was 15.0 Gy (range, 7.0-32.0) delivered in twice-daily fractions of 6.0-8.0 Gy in 4 patients and in once-daily fractions of 7.0-15.0 Gy in 12 patients, respectively. RESULTS: After a median followup of 12.5 months, median overall survival and local control was 12.9 and 24.9 months, respectively. The corresponding median overall survival and local control rates at 1, 2, and 3 years were 56.2%, 37.5%, and 12.5% as well as 68.9%, 57.4%, and 43%, respectively. Apart from one Grade 1 cough episode persisting for 1 week and one patient developing a minor hemopneumothorax requiring no postprocedural drainage, no other adverse events were recorded. CONCLUSIONS: CT-guided interstitial HDR brachytherapy is a safe modality for radiation dose escalation which may play a role in the definitive radiotherapy treatment of locally advanced NSCLC.

Cyanide and lactate levels in patients during chronic oral amygdalin intake followed by intravenous amygdalin administration.

The natural compound amygdalin has gained high popularity among tumor patients as a complementary or alternative treatment option. However, due to metabolization of amygdalin to cyanide (HCN) following oral consumption, there could be a high risk of lactic acidosis caused by cyanide intoxication. The present retrospective study was undertaken to evaluate cyanide blood and lactate plasma levels of tumor patients (n = 55) before and after intravenous (i.v.) amygdalin infusion. All patients had also continuously ingested amygdalin tablets (3 x 500 mg/day), excepting on the days of i.v. administration. Each patient received one to five intravenous amygdalin treatments. The time period between each i.v. application ranged between 4-6 days. The initial i.v. dose was 6 mg (n = 28), 9 mg (n = 1), 15 mg (n = 1) or 18 mg (n = 25). The mean cyanide blood level before i.v. amygdalin administration was 34.74 µg/L, which increased significantly to a mean value of 66.20 µg/L after i. v. amygdalin application. In contrast, lactate decreased significantly from 1266 µmol/L pre-infusion to 868 µmol/L post-infusion. Increasing i.v. amygdalin by 1 mg was also associated with a significant increase in the cyanide level, while the lactate blood level significantly decreased. This is the first study evaluating cyanide levels under conditions employed by amygdalin administrators, i.e. after chronic oral amygdalin intake and then again after a closely subsequent intravenous amygdalin administration. Since lactate decreased, whilst cyanide increased, it is concluded that elevation of cyanide does not induce metabolic acidosis in terms of an increased lactate level.

Downregulation of SPTAN1 is related to MLH1 deficiency and metastasis in colorectal cancer.

INTRODUCTION: Colorectal cancers (CRCs) deficient in the DNA mismatch repair protein MutL homolog 1 (MLH1) display distinct clinicopathological features and require a different therapeutic approach compared to CRCs with MLH1 proficiency. However, the molecular basis of this fundamental difference remains elusive. Here, we report that MLH1-deficient CRCs exhibit reduced levels of the cytoskeletal scaffolding protein non-erythroid spectrin αII (SPTAN1), and that tumor progression and metastasis of CRCs correlate with SPTAN1 levels. METHODS AND RESULTS: To investigate the link between MLH1 and SPTAN1 in cancer progression, a cohort of 189 patients with CRC was analyzed by immunohistochemistry. Compared with the surrounding normal mucosa, SPTAN1 expression was reduced in MLH1-deficient CRCs, whereas MLH1-proficient CRCs showed a significant upregulation of SPTAN1. Overall, we identified a strong correlation between MLH1 status and SPTAN1 expression. When comparing TNM classification and SPTAN1 levels, we found higher SPTAN1 levels in stage I CRCs, while stages II to IV showed a gradual reduction of SPTAN1 expression. In addition, SPTAN1 expression was lower in metastatic compared with non-metastatic CRCs. Knockdown of SPTAN1 in CRC cell lines demonstrated decreased cell viability, impaired cellular mobility and reduced cell-cell contact formation, indicating that SPTAN1 plays an important role in cell growth and cell attachment. The observed weakened cell-cell contact of SPTAN1 knockdown cells might indicate that tumor cells expressing low levels of SPTAN1 detach from their primary tumor and metastasize more easily. CONCLUSION: Taken together, we demonstrate that MLH1 deficiency, low SPTAN1 expression, and tumor progression and metastasis are in close relation. We conclude that SPTAN1 is a candidate molecule explaining the tumor progression and metastasis of MLH1-deficient CRCs. The detailed analysis of SPTAN1 is now mandatory to substantiate its relevance and its potential value as a candidate protein for targeted therapy, and as a predictive marker of cancer aggressiveness.

Comparison of strain elastography, point shear wave elastography using acoustic radiation force impulse imaging and 2D-shear wave elastography for the differentiation of thyroid nodules.

PURPOSE: The aim of the study was to compare three different elastography methods, namely Strain Elastography (SE), Point Shear-Wave Elastography (pSWE) using Acoustic Radiation Force Impulse (ARFI)-Imaging and 2D-Shear Wave Elastography (2D-SWE), in the same study population for the differentiation of thyroid nodules. MATERIALS AND METHODS: All patients received a conventional ultrasound scan, SE and 2D-SWE, and all patients except for two received ARFI-Imaging. Cytology/histology of thyroid nodules was used as a reference method. SE measures the relative stiffness within the region of interest (ROI) using the surrounding tissue as reference tissue. ARFI mechanically excites the tissue at the ROI using acoustic pulses to generate localized tissue displacements. 2D-SWE measures tissue elasticity using the velocity of many shear waves as they propagate through the tissue. RESULTS: 84 nodules (73 benign and 11 malignant) in 62 patients were analyzed. Sensitivity, specificity and NPV of SE were 73%, 70% and 94%, respectively. Sensitivity, specificity and NPV of ARFI and 2D-SWE were 90%, 79%, 98% and 73%, 67%, 94% respectively, using a cut-off value of 1.98m/s for ARFI and 2.65m/s (21.07kPa) for 2D-SWE. The AUROC (Area under the Receiver Operating Characteristic) of SE, ARFI and 2D-SWE for the diagnosis of malignant thyroid nodules were 52%, 86% and 71%, respectively. A significant difference in AUROC was found between SE and ARFI (p = 0.008), while no significant difference was found between ARFI and SWE (86% vs. 71%, p = 0.31), or SWE and SE (71% vs. 52%, p = 0.26). CONCLUSION: pSWE using ARFI and 2D-SWE showed comparable results for the differentiation of thyroid nodules. ARFI was superior to elastography using SE.

Inverse planning and inverse implanting for breast interstitial brachytherapy. Introducing a new anatomy specific breast interstitial template (ASBIT).

An innovative template, based on thoracic cage surface reconstructions for breast interstitial brachytherapy was developed. Hybrid-inverse-planning-optimisation-based implantations and brachytherapy plans, using three custom anthropomorphic breast phantoms, were utilised for its validation. A user independent, inverse planning and inverse implanting technique is proposed.

Patterns of care analysis for head & neck cancer of unknown primary site: a survey inside the German society of radiation oncology (DEGRO).

BACKGROUND: Due to the absence of randomized trials, the optimal management for squamous cell cancer of unknown primary in the head and neck region (SCCHN CUP) remains controversial. Current strategies are based on retrospective studies, clinical experience, and institutional policies. METHODS: An anonymous questionnaire with a total of 24 questions was created and distributed by the use of an online version (Google Forms®, Google, Mountain View, CA, USA) as well as a printout version as equivalent option. An email with a link to the survey and the questionnaire as attachment was sent to 361 DEGRO(German Society of Radiation Oncology)-associated departments. Frequency distributions of responses for each question were calculated. The data were also analyzed by type of practice. Representativity of the sample size for the DEGRO was also evaluated. RESULTS: 66 responses were received including answers from 20 (30%) university departments, 16 (24%) non-university institutions, and 30 (46%) radiation oncology practices. 95% of the participants routinely present these cases in an interdisciplinary tumor board and use intensity modulated radiotherapy (IMRT) techniques for SCCHN CUP treatment. Surgery includes neck dissection in 83% and tonsillectomy in 73% of the cases. Human papilloma virus (HPV) status is routinely determined in 82% of the departments. Statistically significant differences between universities and institutions and clinics and practices could be found with respect to positron emission tomography-computed tomography (PET-CT) utilization, indications for chemotherapy, radiotherapy volumes, and cumulative doses. CONCLUSION: Diagnostics and treatment for SCCHN CUP within the DEGRO remain heterogeneous. A prospective register trial with standard operation procedures is warranted to homogenize and possibly improve management.

Combined high dose rate brachytherapy and external beam radiotherapy for clinically localised prostate cancer.

PURPOSE: To report the clinical outcomes and treatment-related toxicities after combined high-dose-rate (HDR) brachytherapy (BRT) with external beam radiotherapy (EBRT) for patients with clinically localised high-risk prostate cancer. MATERIAL AND METHODS: Between 2008 and 2012, three hundred and three consecutive patients with organ-confined high-risk prostate cancer were treated with definitive radiotherapy consisting of HDR-BRT followed by supplemental EBRT. The transrectal 3D-ultrasound-based HDR-BRT boost consisted of two single-fraction implants of 10.5 Gy, prescribed to the 90% of the gland (D90), for a total physical dose of 21.0 Gy delivered to the prostatic gland. EBRT was delivered with conventional fractionation, prescribing 45.0 Gy to the prostatic gland and seminal vesicles. Biochemical failure was defined according to the Phoenix Consensus Criteria, genitourinary (GU)/gastrointestinal (GI) toxicity was evaluated using the Common Toxicity Criteria for Adverse Events (version 3.0). RESULTS: The median follow-up was 71.6 months. The 7-year overall survival, biochemical control and metastasis-free-survival rates for the entire cohort were 85.7%, 88.3% and 93.8%, respectively. Androgen deprivation therapy was initiated prior to treatment for 92.7% of patients with a median duration of 12 months. Toxicity was scored per event with late Grade 2, 3 and 4 GU adverse events and was found to be 15.3%, 2.2% and 0.3%, respectively. Late Grade 2 GI toxicity accounted for 0.3% with no instances of Grade 3 or higher late adverse events. CONCLUSION: HDR-BRT with supplemental EBRT results in low biochemical relapse-free survival rates associated with a very low incidence of higher-grade late adverse events.

High dose rate brachytherapy as monotherapy for localised prostate cancer.

BACKGROUND AND PURPOSE: To evaluate the oncological outcome of a three-implant high dose rate (HDR) brachytherapy (BRT) protocol as monotherapy for clinically localised prostate cancer. MATERIAL AND METHODS: Between February 2008 and December 2012, 450 consecutive patients with clinically localised prostate cancer were treated with HDR monotherapy. The cohort comprised of 198 low-, 135 intermediate- and 117 high risk patients being treated with three single-fraction implants of 11.5Gy delivered to an intraoperative real-time, transrectal ultrasound defined planning treatment volume up to a total physical dose of 34.5Gy with an interfractional interval of 21days. Fifty-eight patients (12.8%) received ADT, 32 of whom were high- and 26 intermediate-risk. Biochemical failure was defined according to the Phoenix Consensus Criteria and genitourinary/gastrointestinal toxicity evaluated using the Common Toxicity Criteria for Adverse Events version 3.0. RESULTS: The median follow-up time was 56.3months. The 60-month overall survival, biochemical control and metastasis-free-survival rates were 96.2%, 95.0% and 99.0%, respectively. Toxicity was scored per event with late Grade 2 and 3 genitourinary adverse events of 14.2% and 0.8%, respectively. Late Grade 2 gastrointestinal toxicity amounted 0.4% with no instances of Grade 3 or greater late adverse events to be reported. CONCLUSIONS: Our results confirm HDR BRT to be a safe and effective monotherapeutic treatment modality for clinically localised prostate cancer.

Evaluation of 2D- Shear Wave Elastography for Characterisation of Focal Liver Lesions.

BACKGROUND AND AIM: This is a prospective study for evaluation of 2D-shear wave elastography (2D-SWE) for characterisation and differentiation of benign und malignant focal liver lesions (FLLs). METHODS: The patients referred to our ultrasound unit were prospectively included. B-mode ultrasound and 2D-SWE (Aixplorer® France) were performed for one FLL in each patient. Liver histology and/or contrast-enhanced imaging were used as a reference method. RESULTS: 140 patients with FLL were included. SWE acquisitions failed in 24% of them. Therefore, 106 patients with FLL could be analysed, 42/106 with benign and 64/106 with malignant FLLs. The median stiffness for benign FLLs was 16.4 (2.1-71.9) kPa: 16.55 kPa for 18 focal nodular hyperplasia (FNH), 16.35 kPa for 18 hemangioma, 9.8 kPa for 3 focal fatty sparings (FFS), 8.9 kPa for 1 adenoma, 20 kPa for one regenerative node and 29 kPa for one cholangiofibroma, and for the malignant FLLs 36 (4.1-142.9) kPa: 44.8 kPa for 16 hepatocellular carcinoma (HCC), 70.7 kPa for 7 cholangiocarcinoma (CCC) and 29.5 kPa for the 41 metastasis (p<0.001). Malignant FLLs were significantly stiffer than benign FLLs (p<0.0001). Cholangiocarcinomas were the stiffest malignant FFLs with significantly higher values as compared to HCCs and metastases (p=0.033 and p=0.0079, respectively). No significant difference in stiffness could be observed between the different benign FLL entities. No significant difference was observed whether 2D-SWE included the whole FLL, the periphery or only the hardest area of the FLL. CONCLUSIONS: 2D-SWE provides further characterising information for interpretation of FLLs and may be useful at least in differentiation of CCCs and HCCs.

Photobiomodulation therapy for the management of radiation-induced dermatitis : A single-institution experience of adjuvant radiotherapy in breast cancer patients after breast conserving surgery.

BACKGROUND: Radiation therapy (RT) comprises a key component in the treatment of breast cancer. Radiation-induced skin toxicity is the major adverse event experienced by patients; however, radiodermatitis (RD) prevention and management remains trivial. It is proven that photobiomodulation (PBM) therapy using light-emitting diode (LED) increases wound healing and depicts an anti-inflammatory effect. This single-institute study evaluates the beneficial role of PBM-LED in preventing/reducing RD during breast cancer RT. PATIENTS AND METHODS: Of 70 consecutively treated patients, 25 patients were treated with PBM-LED twice a week prior to adjuvant 3D conformal RT after breast-conserving surgery. RD was reported using Common Toxicity Criteria for Adverse Events Version 4.0 and pain intensity using a visual analog scale (VAS). For comparison, a control group (n = 45) received RT without PBM-LED. In addition, a "matched" group (n = 25) was generated from the control group based on propensity for potentially confounding variables. RESULTS: In the PBM group, 22 patients (88%) presented grade 1 and 3 (12%) grade 2 RD. In the control group, 25 patients (55.6%) developed grade 1 reactions, 18 patients (40%) grade 2, and 2 (4.4%) patients grade 3 RD. Concerning pain intensity, 15 patients (60%) of the PBM treatment arm reported no pain, 5 patients (20%) VAS 2, and 5 (20%) VAS 3. In the control group, 13 patients (28.9%) reported no pain, 2 (4.4%) VAS 1, 7 (15.6%) VAS 2, 9 patients (20%) reported VAS 3, 12 (26.7%) patients VAS 4, and 2 (4.4%) patients VAS 5. CONCLUSION: PBM-LED therapy applied prior to RT might be effective in decreasing the incidence and sequelae of radiation-induced skin toxicity in breast cancer patients treated with breast-conserving surgery.

Persistence of HCV in Acutely-Infected Patients Depletes C24-Ceramide and Upregulates Sphingosine and Sphinganine Serum Levels.

Hepatitis C virus (HCV) substantially affects lipid metabolism, and remodeling of sphingolipids appears to be essential for HCV persistence in vitro. The aim of the current study is the evaluation of serum sphingolipid variations during acute HCV infection. We enrolled prospectively 60 consecutive patients with acute HCV infection, most of them already infected with human immunodeficiency virus (HIV), and serum was collected at the time of diagnosis and longitudinally over a six-month period until initiation of antiviral therapy or confirmed spontaneous clearance. Quantification of serum sphingolipids was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Spontaneous clearance was observed in 11 out of 60 patients (18.3%), a sustained viral response (SVR) in 43 out of 45 patients (95.5%) receiving an antiviral treatment after follow-up, whereas persistence of HCV occurred in six out of 60 patients (10%). C24-ceramide (C24-Cer)-levels increased at follow-up in patients with spontaneous HCV eradication (p < 0.01), as compared to baseline. Sphingosine and sphinganine values were significantly upregulated in patients unable to clear HCV over time compared to patients with spontaneous clearance of HCV infection on follow-up (p = 0.013 and 0.006, respectively). In summary, the persistence of HCV after acute infection induces a downregulation of C24Cer and a simultaneous elevation of serum sphingosine and sphinganine concentrations.

Investigation of NS3 Protease Resistance-Associated Variants and Phenotypes for the Prediction of Treatment Response to HCV Triple Therapy.

Triple therapy of chronic hepatitis C virus (HCV) infection with boceprevir (BOC) or telaprevir (TVR) leads to virologic failure in many patients which is often associated with the selection of resistance-associated variants (RAVs). These resistance profiles are of importance for the selection of potential rescue treatment options. In this study, we sequenced baseline NS3 RAVs population-based and investigated the sensitivity of NS3 phenotypes in an HCV replicon assay together with clinical factors for a prediction of treatment response in a cohort of 165 German and Swiss patients treated with a BOC or TVR-based triple therapy. Overall, the prevalence of baseline RAVs was low, although the frequency of RAVs was higher in patients with virologic failure compared to those who achieved a sustained virologic response (SVR) (7% versus 1%, P = 0.06). The occurrence of RAVs was associated with a resistant NS3 quasispecies phenotype (P<0.001), but the sensitivity of phenotypes was not associated with treatment outcome (P = 0.2). The majority of single viral and host predictors of SVR was only weakly associated with treatment response. In multivariate analyses, low AST levels, female sex and an IFNL4 CC genotype were independently associated with SVR. However, a combined analysis of negative predictors revealed a significantly lower overall number of negative predictors in patients with SVR in comparison to individuals with virologic failure (P<0.0001) and the presence of 2 or less negative predictors was indicative for SVR. These results demonstrate that most single baseline viral and host parameters have a weak influence on the response to triple therapy, whereas the overall number of negative predictors has a high predictive value for SVR.

Patient Blood Management is Associated With a Substantial Reduction of Red Blood Cell Utilization and Safe for Patient's Outcome: A Prospective, Multicenter Cohort Study With a Noninferiority Design.

OBJECTIVE: To determine whether the implementation of patient blood management (PBM) is effective to decrease the use of red blood cell without impairment of patient's safety. BACKGROUND: The World Health Organization encouraged all member states to implement PBM programs employing multiple combined strategies to increase and preserve autologous erythrocyte volume to minimize red blood cell transfusions. Data regarding safety issues are not sufficiently available. METHODS: In this prospective, multicenter study, surgical inpatients from four German University Hospitals were analyzed before (pre-PBM) and after the implementation of PBM. PBM program included multiple measures (ie, preoperative optimization of hemoglobin levels, blood-sparing techniques, and standardization of transfusion practice). Primary aim was to show noninferiority of the PBM cohort with a margin of 0.5%. Secondary endpoints included red blood cell utilization. RESULTS: A total of 129,719 patients discharged between July 2012 and June 2015 with different inclusion periods for pre-PBM (54,513 patients) and PBM (75,206 patients) were analyzed. The primary endpoint was 6.53% in the pre-PBM versus 6.34% in the PBM cohort. The noninferiority aim was achieved (P < 0.001). Incidence of acute renal failure decreased in the PBM cohort (2.39% vs 1.67%; P < 0.001, regression model). The mean number of red blood cell transfused per patient was reduced from 1.21 ±â€Š0.05 to 1.00 ±â€Š0.05 (relative change by 17%, P < 0.001). CONCLUSIONS: The data presented show that implementation of PBM with a more conscious handling of transfusion practice can be achieved even in large hospitals without impairment of patient's safety. Further studies should elucidate which PBM measures are most clinically and cost effective. TRIAL REGISTRATION: PBM-Study ClinicalTrials.gov, NCT01820949.

Intraductal biopsies in indeterminate biliary stricture: Evaluation of histopathological criteria in fluoroscopy- vs. cholangioscopy guided technique.

BACKGROUND: Differentiating malignancy from benign disease in indeterminate biliary stricture by imaging modalities is limited. Definite diagnosis relies on histopathological diagnosis. AIMS: To assess accuracy of histopathological diagnosis of fluoroscopy-guided vs. cholangioscopy-directed intraductal biopsies in indeterminate biliary stricture. METHODS: All patients with indeterminate biliary stricture and fluoroscopically (n=68) or cholangioscopy-directed (working channel 2mm, n=38) biopsies were included. Histopathological results of biopsies were classified into inflammatory lesion (class 1), dysplasia/intraepithelial neoplasia (class 2) and malignancy (class 3) and results as well as macroscopic diagnosis were compared with final diagnosis. RESULTS: Sensitivity and specificity of fluoroscopy-guided vs. cholangioscopy-directed biopsies were 22.9% and 100% vs. 25.0% and 100% for class 1+2 vs. class 3 lesions, respectively. Sensitivity for class 1 vs. class 2+3 lesions was 45.7% (p=0.044) vs. 58.3% (p=0.214) for fluoroscopy-guided vs. cholangioscopy-directed biopsies, respectively, while specificity was 100% in both. There was no difference in size of the obtained sample (p=0.992). True positive diagnosis rate increased with the number of biopsies taken (p=0.028). CONCLUSION: Fluoroscopy-guided and cholangioscopy-directed intraductal biopsies are equally limited in establishing the diagnosis of malignancy in indeterminate biliary stricture. Categorizing dysplasia or intraepithelial neoplasia as malignancy increases sensitivity without decrease in specificity. By taking more biopsies, diagnostic yield is increased.

Clinical Efficacy of Simulated Vitreoretinal Surgery to Prepare Surgeons for the Upcoming Intervention in the Operating Room.

PURPOSE: To evaluate the efficacy of the virtual reality training simulator Eyesi to prepare surgeons for performing pars plana vitrectomies and its potential to predict the surgeons' performance. METHODS: In a preparation phase, four participating vitreoretinal surgeons performed repeated simulator training with predefined tasks. If a surgeon was assigned to perform a vitrectomy for the management of complex retinal detachment after a surgical break of at least 60 hours it was randomly decided whether a warmup training on the simulator was required (n = 9) or not (n = 12). Performance at the simulator was measured using the built-in scoring metrics. The surgical performance was determined by two blinded observers who analyzed the video-recorded interventions. One of them repeated the analysis to check for intra-observer consistency. The surgical performance of the interventions with and without simulator training was compared. In addition, for the surgeries with simulator training, the simulator performance was compared to the performance in the operating room. RESULTS: Comparing each surgeon's performance with and without warmup trainingshowed a significant effect of warmup training onto the final outcome in the operating room. For the surgeries that were preceeded by the warmup procedure, the performance at the simulator was compared with the operating room performance. We found that there is a significant relation. The governing factor of low scores in the simulator were iatrogenic retinal holes, bleedings and lens damage. Surgeons who caused minor damage in the simulation also performed well in the operating room. CONCLUSIONS: Despite the large variation of conditions, the effect of a warmup training as well as a relation between the performance at the simulator and in the operating room was found with statistical significance. Simulator training is able to serve as a warmup to increase the average performance.