Analysis of Player Performance and Financial Costs Associated With Implementation of an Updated National Hockey League Concussion Protocol: A Retrospective Comparative Study.

Background: An updated National Hockey League (NHL) concussion protocol (NHLCP) was established in the 2016-2017 season to mitigate the negative outcomes of sport-related concussions. However, few studies on the effects of implementing the NHLCP have been performed. Purpose: To define concussion incidence and investigate differences in NHL player performance after a concussion during periods before and after NHLCP implementation and assess the financial impact on NHL teams associated with NHLCP implementation. Study Design: Cohort study; Level of evidence, 3. Methods: This was a retrospective review of NHL players who sustained a concussion before (2000-2001 to 2015-2016 seasons) and after (2016-2017 to 2020-2021 seasons) implementing the NHLCP (pre-NHLCP and post-NHLCP groups). For each group, multiple performance metrics-including 30 days, 1 season, and 3 seasons before and after concussion-were compared for both groups. Return to play, total concussion cost, and association of return to play with cost were investigated using regression analysis. Results: A total of 452 players (423 skaters, 29 goalies) sustained concussions during the study period, including 331 players (315 skaters, 16 goalies) in the pre-NHLCP group and 121 players (108 skaters, 13 goalies) in the post-NHLCP group. For both groups, no significant differences in standard performance were observed during the 30-day and 1-season periods before and after concussion. The mean return to play was significantly higher in the pre-NHLCP group than in the post-NHLCP group (20.1 vs 15.7 days; P = .022). The mean adjusted player salary was not different between groups; nonetheless, the mean adjusted replacement player salary was significantly higher in the post-NHLCP group ($744,505 vs $896,942; P = .032). The mean cost of time missed did not differ between groups. The mean return to play time significantly decreased over the entire study period (R2 = 0.33; P = .005), and the mean return to play time was positively associated with cost R2 = 0.215; P = .030). Conclusion: Concussion incidence did not change after implementation of the updated NHLCP; nonetheless, players had significantly less missed time from injury after protocol implementation. Changes in player performance 30 days and 1 year before and after concussion injury were not different before and after NHLCP implementation. No differences were found in the financial cost of concussions between the pre- and post-NHLCP groups, and missed time was significantly correlated with mean cost from missed time.

Angiogenic factors and the lectin pathway of complement in women with secondary recurrent pregnancy loss.

The poor remodeling of placental spiral arteries seen in preeclampsia is also discussed to contribute to recurrent pregnancy loss (RPL) preceded by abnormal angiogenesis and excessive complement activation. Low levels of Mannose-binding-lectin (MBL), a pattern recognition molecule (PRM) of the lectin pathway, have been found in women with RPL. We propose that pregnancy loss is connected to defective angiogenesis with reperfusion damage in the placenta and decreased levels of PRM in the lectin pathway in women with RPL. In this cohort study, we investigate the angiogenic factors and the lectin complement pathway in early pregnancy and their time-dependent relationship with pregnancy outcomes in 76 women with secondary RPL (sRPL) who have at least four prior pregnancy losses and a live birth. We evaluated levels of Angiopoietin-1 (Ang-1), Angiopoietin-2 (Ang-2), Vascular Endothelial Growth Factor (VEGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and the PRMs, MBL, ficolin-1, -2, -3 and an additional soluble PRM, Pentraxin-3, during the 5th, 6th, and 7th gestational weeks. Our results showed that, compared to live births, pregnancies that ended in loss were associated with elevated VEGF levels and decreased levels of the Ang-2/Ang-1 ratio. Also, increasing levels of ficolin-2 were significantly associated with pregnancy loss, with MBL showing no association. Our research suggests that women with sRPL may have inadequate placentation with impaired angiogenesis in pregnancies ending in a loss.

Return to Play, Performance, and Earnings Analysis After Lumbar Disc Herniation in National Hockey League Players.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Professional hockey players have a high incidence of lumbar disc herniations (LDH). The purpose of this study was to determine the impact of LDH on the performance and financial earnings of National Hockey League (NHL) players. METHODS: NHL players who sustained a LDH were retrospectively reviewed utilizing an online database and a 2:1 matched control cohort. Player performance and game usage was compared at one- and three-season(s) pre- and post-injury season within the cohorts. Injured and matched players were divided into 3 groups based on the player's adjusted index season salary. RESULTS: A total of 181 players were included, with 62 LDH players matched to 119 healthy controls. Return to play after LDH was 79%. The LDH cohort had fewer seasons played throughout their career compared to the matched group (12.5 ± 4.3 vs 14.2 ± 3.8; P = .031). At 1 season post-index, the LDH cohort had significantly fewer goals per 60 and points per 60 when compared to pre-index. At 3 seasons post-index, the LDH cohort exhibited a significant decline in time-on-ice per game played, goals per 60, and points per 60 compared to pre-index. CONCLUSION: The majority of NHL players who sustained a LDH returned to play (79%) but had shorter careers overall and decreased performance outcomes when compared to matched cohorts at both 1 and 3 seasons post-injury.

Effects of the COVID-19 Pandemic on Humeral Shaft Fracture Management and Its Outcomes.

Background and objective The coronavirus disease 2019 (COVID-19) pandemic necessitated a sudden and drastic shift in patient management throughout the healthcare system, to curb the spread of the disease and deal with resource limitations. Many surgical cases were canceled or delayed with only the most urgent and emergent cases taken up for treatment. It is unknown if and how these alterations affected patient outcomes. The purpose of this study was to compare time to fracture care and outcomes between patients treated for humeral shaft fractures prior to the COVID-19 pandemic and those treated during the pandemic. We hypothesized that the pandemic cohort would have a prolonged time to fracture care and worse outcomes than the pre-pandemic cohort. Materials and methods This was a retrospective cohort study performed within a single healthcare system. All humeral shaft fractures treated from March to June 2019 (pre-pandemic cohort) and March to June 2020 (pandemic cohort) were identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes and ICD-10-CM codes as well as Current Procedural Terminology (CPT) codes. Data on demographics, fracture characteristics, treatment, and outcomes were collected via chart and radiograph review. Outcomes analyzed included time to being made weight-bearing as tolerated (WBAT), radiographic union, and final follow-up; range of motion (ROM) at radiographic union and final follow-up; and rate of complications. Results The pre-pandemic cohort (n=19) was significantly younger with a mean age of 29 years than the pandemic cohort (n=17) with a mean age of 49 years (p=0.010). There were no other significant differences in demographics, fracture characteristics, or treatment type between the groups. Time to fracture care was not significantly different in the pre-pandemic cohort (five days) versus the pandemic cohort (four days). Time to being made WBAT, radiographic union, and final follow-up were not significantly different between the pre-pandemic (86, 113, and 98 days) and the pandemic cohorts (77, 106, and 89.5 days). ROM measurements in abduction at radiographic union were significantly different between the cohorts: in the pre-pandemic cohort, 100% of patients reached greater than 160 degrees; in the pandemic cohort, only 16.7% of patients reached greater than 160 degrees (p=0.048). There was a non-significant decrease in the proportion of patients who achieved the maximal category of ROM measurements in forward elevation and extension at radiographic union and abduction, forward elevation, and extension at final follow-up, as well as a non-significant increase in visual analog scale (VAS) pain scores at final follow-up between cohorts. There were no significant differences in the rate of complications. Conclusions Despite limited resources, reduced operating room availability, and increased utilization of virtual visits due to the COVID-19 pandemic, patients with humeral shaft fractures may not have faced delays in fracture care or worse outcomes compared to the pre-pandemic period. The pandemic cohort may have experienced significantly decreased ROM compared to the pre-pandemic cohort, which may reflect the decreased availability of physical therapy services and overall decreased activity levels due to the quarantine orders. However, we could not identify any other significant differences in the type of treatment, pain, complications, or time to union.

In vivo / in vitro Correlation of Pharmacokinetics of Gentamicin, Vancomycin, Teicoplanin and Doripenem in a Bovine Blood Hemodialysis Model.

Background: Elimination of a drug during renal replacement therapy is not only dependent on flow rates, molecular size and protein binding, but is often influenced by difficult to predict drug membrane interactions. In vitro models allow for extensive profiling of drug clearance using a wide array of hemofilters and flow rates. We present a bovine blood based in vitro pharmacokinetic model for intermittent renal replacement therapy. Methods: Four different drugs were analyzed: gentamicin, doripenem, vancomicin and teicoplanin. The investigated drug was added to a bovine blood reservoir connected to a hemodialysis circuit. In total seven hemofilter models were analyzed using commonly employed flow rates. Pre-filter, post-filter and dialysate samples were drawn, plasmaseparated and analyzed using turbidimetric assays or HPLC. Protein binding of doripenem and vancomycin was measured in bovine plasma and compared to previously published values for human plasma. Results: Clearance values were heavily impacted by choice of membrane material and surface as well as by dialysis parameters such as blood flow rate. Gentamicin clearance ranged from a minimum of 90.12 ml/min in a Baxter CAHP-170 diacetate hemofilter up to a maximum of 187.90 ml/min in a Fresenius medical company Fx80 polysulfone model (blood flow rate 400 ml/min, dialysate flow rate 800 ml/min). Clearance of Gentamicin vs Vancomicin over the F80s hemofilter model using the same flow rates was 137.62 mL vs 103.25 ml/min. Doripenem clearance with the Fx80 was 141.25 ml/min. Conclusion: Clearance values corresponded very well to previously published data from clinical pharmacokinetic trials. In conjunction with in silico pharmacometric models. This model will allow precise dosing recommendations without the need of large scale clinical trials.

Plasma and Lung Tissue Pharmacokinetics of Ceftaroline Fosamil in Patients Undergoing Cardiac Surgery with Cardiopulmonary Bypass: an In Vivo Microdialysis Study.

Ceftaroline fosamil, a fifth-generation cephalosporin antibiotic with activity against methicillin-resistant Staphylococcus aureus (MRSA), is currently approved for the treatment of pneumonia and complicated skin and soft tissue infections. However, pharmacokinetics data on free lung tissue concentrations in critical patient populations are lacking. The aim of this study was to evaluate the pharmacokinetics of the high-dose regimen of ceftaroline in plasma and lung tissue in cardiac surgery patients during intermittent and continuous administration. Nine patients undergoing elective cardiac surgery on cardiopulmonary bypass were included in this study and randomly assigned to intermittent or continuous administration. Eighteen hundred milligrams of ceftaroline fosamil was administered intravenously as either 600 mg over 2 h every 8 h (q8h) (intermittent group) or 600 mg over 2 h (loading dose) plus 1,200 mg over 22 h (continuous group). Interstitial lung tissue concentrations were measured by in vivo microdialysis. Relevant pharmacokinetics parameters were calculated for each group. Plasma exposure levels during intermittent and continuous administration were comparable to those of previously published studies and did not differ significantly between the two groups. In vivo microdialysis demonstrated reliable and adequate penetration of ceftaroline into lung tissue during intermittent and continuous administration. The steady-state area under the concentration-time curve from 0 to 8 h (AUCss 0-8) and the ratio of AUCSS 0-8 in lung tissue and AUC in plasma (AUClung/plasma) were descriptively higher in the continuous group. Continuous administration of ceftaroline fosamil achieved a significantly higher proportion of time for which the free drug concentration remained above 4 times the minimal inhibitory concentration (MIC) during the dosing interval (% fT>4xMIC) than intermittent administration for pathogens with a MIC of 1 mg/liter. Ceftaroline showed adequate penetration into interstitial lung tissue of critically ill patients undergoing major cardiothoracic surgery, supporting its use for pneumonia caused by susceptible pathogens.

[Implementation of Enhanced Recovery after Surgery (ERAS®) protocol in radical cystectomy at the University Medical Center Mainz]. / Implementierung des ERAS®-Protokolls (Enhanced Recovery After Surgery) nach radikaler Zystektomie an der Universitätsmedizin Mainz.

BACKGROUND: In surgical fields there has been a perceivable paradigm shift during the last decade concerning patient pre- and rehabilitation. Current literature suggests close interdisciplinary collaboration after complex procedures such as radical cystectomy in order to optimize perioperative patient care for the benefit of "fast-track" surgery. OBJECTIVES: To compose a catalogue of standardized measures after radical cystectomy based on guidelines set by the ERAS®-Society. RESULTS: The protocol commences with preoperative education in order to improve the physical and psychological condition of the patient. Crucial aspects in peri- and postoperative patient care are gentle surgical technique, adequate pain management, early mobilization and oral food intake, early removal of drains and foreign material and a seamless return to normal, daily life. CONCLUSIONS: Prospective data analysis will be the next step in order to establish the effectiveness of the protocol especially regarding postoperative complications and median duration of hospital stay.

Robot-assisted simple prostatectomy versus open simple prostatectomy: a single-center comparison.

PURPOSE: Open simple prostatectomy (OSP) is a standard surgical technique for patients with benign prostatic hyperplasia with prostate size larger than 80 ml. As a minimally invasive approach, robot-assisted simple prostatectomy (RASP) emerged as a feasible surgical alternative. Currently, there are no definite recommendations for the standard use of RASP. Therefore, we aimed at investigating various clinical outcomes comparing RASP with OSP. METHODS: In this retrospective single-center study, we evaluated clinical data from 103 RASP and 31 OSP patients. Both cohorts were compared regarding different clinical characteristics with and without propensity score matching. To detect independent predictive factors for clinical outcomes, multivariate logistic regression analysis was performed. RESULTS: Robot-assisted simple prostatectomy patients demonstrated a lower estimated blood loss and need for postoperative blood transfusions as well as less postoperative complications. OSP had a shorter operative time (125 min vs. 182 min) longer hospital stay (11 days vs. 9 days) and longer time to catheter removal (8 days vs. 6 days). In the multivariate analysis, RASP was identified as an independent predictor for longer operative time, lower estimated blood loss, shorter length of hospital stay, shorter time to catheter removal, less postoperative complications and blood transfusions. CONCLUSION: Robot-assisted simple prostatectomy is a safe alternative to OSP with less perioperative and postoperative morbidity. Whether OSP (shorter operative time) or RASP (shorter length of hospital stay) has a more favorable economic impact depends on the particular conditions of different health care systems. Further prospective comparative research is warranted to define the value of RASP in the current surgical management of benign prostatic hyperplasia.

The PT2D-Score: a novel tool to predict complications and economic outcome after radical cystectomy.

BACKGROUND: Radical cystectomy (RC) has a high morbidity and leads to a significant socio-economic burden. We aimed to investigate pre-, intra-, and post-operative variables to create a novel score predicting both post-operative clinical (complications) and economic (length of hospital stay) outcome after RC. METHODS: We retrospectively evaluated clinical and histopathological data of 317 patients after RC. We performed univariate and multivariate logistic regression analyses to identify variables associated with post-operative clinical (30-day morbidity according to Clavien-Dindo complications) and economic (length of hospital stay) outcome. RESULTS: In multivariate analysis, a high number of intraoperative transfusions (T) of packed red blood cells predicted major complications (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.10-2.58, p = 0.017), preoperative potassium (P) level predicted three or more complications (OR for high preoperative potassium 0.71, 95% CI 0.52-0.98, p = 0.037), and high drain (D) loss on post-operative day 1 predicted a longer hospital stay ≥ 22 days (OR 1.57, 95% CI 1.04-2.35, p = 0.003). The PT2D-Score was able to predict three or more complications (area under the curve: 0.70, 95% CI 0.61-0.78, p < 0.001) and a hospital stay of ≥ 22 days in patients after radical cystectomy (area under the curve: 0.63, 95% confidence interval 0.53-0.72, p = 0.012). CONCLUSIONS: The novel PT2D-Score combines preoperative potassium level, intraoperative blood transfusion, and post-operative drain loss to predict both clinical (30-day morbidity) and economic (length of hospital stay) outcome for patients undergoing RC. After validation in a larger cohort, the novel PT2D-Score might serve as an additional criterion to identify patients for intensified monitoring after RC.

Elimination of Doripenem during Dialysis and Pharmacokinetic Evaluation of Posthemodialysis Dosing for Patients Undergoing Intermittent Renal Replacement Therapy.

Doripenem is a broad-spectrum parenteral carbapenem with enhanced activity against Pseudomonas aeruginosa and Enterobacteriaceae Current dosing regimens recommend the administration of 0.25 to 0.5 g once daily in patients undergoing intermittent renal replacement therapy. As patients are usually dialyzed thrice weekly, we aimed to investigate a 1-g posthemodialysis regimen, thus reducing treatment costs and enhancing patient compliance. A second objective of this trial was to describe the pharmacokinetics of intradialytic doripenem. Ten oliguric or anuric patients in need of intermittent renal replacement therapy were included in this trial. All patients suffered from a septic episode. The mean hemofilter clearance was 123.46 ± 42.03 ml/min, and the total body clearance between hemodialysis sessions was 16.79 ± 6.02 ml/min. The average prehemodialysis trough concentration was 2.4 ± 1.3 mg/liter, while the EUCAST resistance breakpoint for Enterobacteriaceae is set at 2 mg/liter. The interpatient variability was considerably higher than the intrapatient variability. Apart from one patient who suffered an allergic reaction, doripenem was tolerated well by all patients. Our data indicate that posthemodialysis administration of 1 g of doripenem results in sufficient plasma levels in anuric but not oliguric patients during the entire dosing interval. (This trial was registered with EudraCT under registration no. 2009-018010-18 and at ClinicalTrials.gov under registration no. NCT02018939.).

[Standard surgery for small renal masses (<4 cm)]. / Standardoperationen bei kleinen Nierentumoren (<4 cm).

BACKGROUND: Several new treatment strategies have emerged in the treatment of small renal masses (<4 cm in diameter). Active surveillance and ablative techniques have been introduced but it remains unclear which patients will benefit the most from these new treatment options. A surgical approach remains standard of care. In recent decades, radical nephrectomy has been replaced by nephron-sparing surgery for the management of small renal masses. RESULTS: In addition to the open partial nephrectomy, which is considered the standard approach, the number of surgeries performed using minimally invasive techniques is increasing. Recent data show that there might be some benefits such as less blood loss. The disadvantages shown by laparoscopic partial nephrectomy such as prolonged warm ischemia, longer operation times, and postoperative renal impairment might be negligible for the robotic approach. Therefore, current guidelines allow these approaches in addition to open partial nephrectomy if sufficient surgical expertise is given.

Concentrations of Cefuroxime in Brain Tissue of Neurointensive Care Patients.

Effective concentrations of antibiotics in brain tissue are essential for antimicrobial therapy of brain infections. However, data concerning cerebral penetration properties of antibiotics for treatment or prophylaxis of central nervous system infections are rare. Six patients suffering subarachnoid hemorrhage and requiring cerebral microdialysis for neurochemical monitoring were included in this study. Free interstitial concentrations of cefuroxime after intravenous application of 1,500 mg were measured by microdialysis in brain tissue, as well as in plasma at steady-state (n = 6) or after single-dose administration (n = 1). At steady state, free area under the concentration-time curve from 0 to 24 h (AUC0-24) values of 389.0 ± 210.3 mg/liter·h and 131.4 ± 72.8 mg/liter·h were achieved for plasma and brain, respectively, resulting in a brain tissue penetration ratio (AUC0-24 brain/AUC0-24 free plasma) of 0.33 ± 0.1. Plasma and brain tissue concentrations at individual time points correlated well (R = 0.59, P = 0.001). At steady-state time over MIC (t>MIC) values of >40% of dosing interval were achieved up to an MIC of 16 mg/liter for plasma and 4 mg/liter for brain tissue. Although MIC90 values could not be achieved in brain tissue for relevant bacteria, current dosing strategies of cefuroxime might be sufficient to treat pathogens with MIC values up to 4 mg/liter. The activity of cefuroxime in brain tissue might be overestimated when relying exclusively on plasma levels. Although currently insufficient data after single dose administration exist, lower brain-plasma ratios observed after the first dose might warrant a loading dose for treatment and perioperative prophylaxis.

Proteomics to predict the response to tumour necrosis factor-α inhibitors in rheumatoid arthritis using a supervised cluster-analysis based protein score.

OBJECTIVE: In rheumatoid arthritis (RA), it is of major importance to identify non-responders to tumour necrosis factor-α inhibitors (TNFi) before starting treatment, to prevent a delay in effective treatment. We developed a protein score for the response to TNFi treatment in RA and investigated its predictive value. METHOD: In RA patients eligible for biological treatment included in the BiOCURA registry, 53 inflammatory proteins were measured using xMAP® technology. A supervised cluster analysis method, partial least squares (PLS), was used to select the best combination of proteins. Using logistic regression, a predictive model containing readily available clinical parameters was developed and the potential of this model with and without the protein score to predict European League Against Rheumatism (EULAR) response was assessed using the area under the receiving operating characteristics curve (AUC-ROC) and the net reclassification index (NRI). RESULTS: For the development step (n = 65 patient), PLS revealed 12 important proteins: CCL3 (macrophage inflammatory protein, MIP1a), CCL17 (thymus and activation-regulated chemokine), CCL19 (MIP3b), CCL22 (macrophage-derived chemokine), interleukin-4 (IL-4), IL-6, IL-7, IL-15, soluble cluster of differentiation 14 (sCD14), sCD74 (macrophage migration inhibitory factor), soluble IL-1 receptor I, and soluble tumour necrosis factor receptor II. The protein score scarcely improved the AUC-ROC (0.72 to 0.77) and the ability to improve classification and reclassification (NRI = 0.05). In validation (n = 185), the model including protein score did not improve the AUC-ROC (0.71 to 0.67) or the reclassification (NRI = -0.11). CONCLUSION: No proteomic predictors were identified that were more suitable than clinical parameters in distinguishing TNFi non-responders from responders before the start of treatment. As the results of previous studies and this study are disparate, we currently have no proteomic predictors for the response to TNFi.

Monocyte gene expression in childhood obesity is associated with obesity and complexity of atherosclerosis in adults.

Childhood obesity coincides with increased numbers of circulating classical CD14++CD16- and intermediate CD14++CD16+ monocytes. Monocytes are key players in the development and exacerbation of atherosclerosis, which prompts the question as to whether the monocytosis in childhood obesity contributes to atherogenesis over the years. Here, we dissected the monocyte gene expression profile in childhood obesity using an Illumina microarray platform on sorted monocytes of 35 obese children and 16 lean controls. Obese children displayed a distinctive monocyte gene expression profile compared to lean controls. Upon validation with quantitative PCR, we studied the association of the top 5 differentially regulated monocyte genes in childhood obesity with obesity and complexity of coronary atherosclerosis (SYNTAX score) in a cohort of 351 adults at risk for ischemic cardiovascular disease. The downregulation of monocyte IMPDH2 and TMEM134 in childhood obesity was also observed in obese adults. Moreover, downregulation of monocyte TMEM134 was associated with a higher SYNTAX atherosclerosis score in adults. In conclusion, childhood obesity entails monocyte gene expression alterations associated with obesity and enhanced complexity of coronary atherosclerosis in adults.

Micafungin Plasma Levels Are Not Affected by Continuous Renal Replacement Therapy: Experience in Critically Ill Patients.

Critically ill patients often experience acute kidney injury and the need for renal replacement therapy in the course of their treatment in an intensive care unit (ICU). These patients are at an increased risk for candidiasis. Although there have been several reports of micafungin disposition during renal replacement therapy, to this date there are no data describing the elimination of micafungin during high-dose continuous venovenous hemodiafiltration with modified AN69 membranes. The aim of this prospective open-label pharmacokinetic study was to assess whether micafungin plasma levels are affected by continuous hemodiafiltration in critical ill patients using the commonly employed AN69 membrane. A total of 10 critically ill patients with micafungin treatment due to suspected or proven candidemia were included in this trial. Prefilter/postfilter micafungin clearance was measured to be 46.0 ml/min (±21.7 ml/min; n = 75 individual time points), while hemofilter clearance calculated by the sieving coefficient was 0.0038 ml/min (±0.002 ml/min; n = 75 individual time points). Total body clearance was measured to be 14.0 ml/min (±7.0 ml/min; n = 12). The population area under the curve from 0 to 24 h (AUC0-24) was calculated as 158.5 mg · h/liter (±79.5 mg · h/liter; n = 13). In spite of high protein binding, no dose modification is necessary in patients receiving continuous venovenous hemodiafiltration with AN69 membranes. A dose elevation may, however, be justified in certain cases. (This study has been registered at ClinicalTrials.gov under identifier NCT02651038.).

Nocturnal resveratrol administration inhibits chemically induced breast cancer formation in rats.

Resveratrol (RES) is well known natural polyphenol with proven antioxidant, antiinflammatory and anticarcinogenic properties. Since mode of application may be important for cancer-preventive effects of RES, the aim of this study was to evaluate a possible delay in the initiation and progression of chemically induced mammary carcinogenesis in female Sprague-Dawley rats after the nocturnal administration of RES. Application of a high dose of RES (100 mg/kg body weight), starting 2 weeks before the first N-methyl-N-nitrosourea dose (NMU) (50 mg/kg body weight), reduced tumor incidence and markedly prolonged latency period (P < 0.01) in the NMU + RES group in comparison to NMU tumor bearing animals. In addition, the tumor volume decreased significantly (P < 0.05) together with tumor frequency (P < 0.05). We also observed that food but not water intake was significantly reduced by 17% between weeks 4 and 12 in the NMU + RES group leading to a pronounced reduction in the body mass of about 25% as compared to untreated controls. In addition to direct effects of RES in tumor tissues, this polyphenol did also improve metabolic functions in RES-treated animals since it normalizes hypoproteinemia and urea levels and increases the number of lymphocytes when compared with NMU. Higher level of reactive oxygen species (ROS) in leukocytes and the elevation of proinflammatory plasma cytokines IL-1 and IL-2 may contribute to the observed reduction in tumor development. These results indicate for the first time that nocturnal administration of a high dose of RES significantly affects tumor development in vivo. Therefore, we conclude that RES is a promising candidate for cancer chemoprevention. However, it should be noted that the mode of application might significantly affect RES ability to fight cancer.

[Urolithiasis 2016 : Reliable, effective and low radiation exposure]. / Steindiagnostik 2016 : Zuverlässig, effektiv und strahlungsarm.

BACKGROUND: Urolithiasis is a widespread disease. Diagnostic imaging plays an important role in the evaluation and management of patients with suspected urolithiasis. Furthermore, modern imaging methods may provide information on stone location, size, fragility and composition aiding the urologist to determine the appropriate treatment modality. PURPOSE: Based on the current literature and guidelines, this review reports on the various new and established diagnostic imaging modalities. RESULTS: Ultrasound should always be the initial imaging modality. Following ultrasound, noncontrast CT-principally using a low-dose protocol-is the imaging modality of choice in the evaluation of patients with acute flank pain and suspected urolithiasis. New imaging modalities like dual energy CT, Uro Dyna CT and digital tomosynthesis are currently under investigation but not yet part of daily clinical practice. Magnetic resonance imaging can be used to detect obstruction caused by urinary stones but is not a first-line imaging modality.

Pilot PET Study to Assess the Functional Interplay Between ABCB1 and ABCG2 at the Human Blood-Brain Barrier.

ABCB1 and ABCG2 work together at the blood-brain barrier (BBB) to limit brain distribution of dual ABCB1/ABCG2 substrates. In this pilot study we used positron emission tomography (PET) to assess brain distribution of two model ABCB1/ABCG2 substrates ([(11) C]elacridar and [(11) C]tariquidar) in healthy subjects without (c.421CC) or with (c.421CA) the ABCG2 single-nucleotide polymorphism (SNP) c.421C>A. Subjects underwent PET scans under conditions when ABCB1 and ABCG2 were functional and during ABCB1 inhibition with high-dose tariquidar. In contrast to the ABCB1-selective substrate (R)-[(11) C]verapamil, [(11) C]elacridar and [(11) C]tariquidar showed only moderate increases in brain distribution during ABCB1 inhibition. This provides evidence for a functional interplay between ABCB1 and ABCG2 at the human BBB and suggests that both ABCB1 and ABCG2 need to be inhibited to achieve substantial increases in brain distribution of dual ABCB1/ABCG2 substrates. During ABCB1 inhibition c.421CA subjects had significantly higher increases in [(11) C]tariquidar brain distribution than c.421CC subjects, pointing to impaired cerebral ABCG2 function.

Screening for thyroid dysfunction and diabetes in patients with carpal tunnel syndrome.

BACKGROUND: Current literature demonstrates that patients with carpal tunnel syndrome (CTS) have a higher prevalence of hypothyroidism and diabetes. The British Society for Surgery of the Hand (BSSH) advises screening CTS patients for thyroid and glucose dysfunction before surgery. This study aimed to analyze the current departmental practice for patients listed for carpal tunnel decompression (CTD) with respect to preoperative assessment of diabetic and thyroid status. METHOD: A retrospective review of all patients who underwent surgery for CTS under one team over a 3 year period (2009-2011) in a UK teaching hospital was performed. Patients' medical records and pathology results were reviewed. RESULTS: A total of 103 procedures were performed in 100 patients. Preoperative thyroid function was checked in 63/100 patients with an abnormal result in 3/63 patients. Two of these patients were subsequently diagnosed with hypothyroidism. Similarly blood glucose was checked in 67/100 patients. This resulted in the new diagnosis of three patients with diabetes. CONCLUSION: The results are consistent with the view that CTS is associated with thyroid dysfunction and diabetes and screening helps in diagnosing new cases of these conditions in this select group. The cost of diagnosing new cases of hypothyroidism and diabetes can be considered as money well spent.