Stereotactic ultrahypofractionated MR-guided radiotherapy for localized prostate cancer - Acute toxicity and patient-reported outcomes in the prospective, multicenter SMILE phase II trial.

Background: Due to superior image quality and daily adaptive planning, MR-guided stereotactic body radiation therapy (MRgSBRT) has the potential to further widen the therapeutic window in radiotherapy of localized prostate cancer. This study reports on acute toxicity rates and patient-reported outcomes after MR-guided adaptive ultrahypofractionated radiotherapy for localized prostate cancer within the prospective, multicenter phase II SMILE trial. Materials and methods: A total of 69 patients with localized prostate cancer underwent MRgSBRT with daily online plan adaptation. Inclusion criteria comprised a tumor stage ≤ T3a, serum PSA value ≤ 20 ng/ml, ISUP Grade group ≤ 4. A dose of 37.5 Gy was prescribed to the PTV in five fractions on alternating days with an optional simultaneous boost of 40 Gy to the dominant intraprostatic lesion defined by multiparametric MRI. Acute genitourinary (GU-) and gastrointestinal (GI-) toxicity, as defined by CTCAE v. 5.0 and RTOG as well as patient-reported outcomes according to EORTC QLQ-C30 and -PR25 scores were analyzed at completion of radiotherapy, 6 and 12 weeks after radiotherapy and compared to baseline symptoms. Results: There were no toxicity-related treatment discontinuations. At the 12-week follow-up visit, no grade 3 + toxicities were reported according to CTCAE. Up until the 12-week visit, in total 16 patients (23 %) experienced a grade 2 GU or GI toxicity. Toxicity rates peaked at the end of radiation therapy and subsided within the 12-week follow-up period. At the 12-week follow-up visit, no residual grade 2 GU toxicities were reported and 1 patient (1 %) had residual grade 2 enteritic symptoms. With exception to a significant improvement in the emotional functioning score following MRgSBRT, no clinically meaningful changes in the global health status nor in relevant subscores were reported. Conclusion: Daily online-adaptive MRgSBRT for localized prostate cancer resulted in an excellent overall toxicity profile without any major negative impact on quality of life.

Improvement of functional outcome for patients with newly diagnosed grade 2 or 3 gliomas with co-deletion of 1p/19q - IMPROVE CODEL: the NOA-18 trial.

BACKGROUND: Given the young age of patients with CNS WHO grade 2 and 3 oligodendrogliomas and the relevant risk of neurocognitive, functional, and quality-of-life impairment with the current aggressive standard of care treatment, chemoradiation with PCV, of the tumour located in the brain optimizing care is the major challenge. METHODS: NOA-18 aims at improving qualified overall survival (qOS) for adult patients with CNS WHO grade 2 and 3 oligodendrogliomas by randomizing between standard chemoradiation with up to six six-weekly cycles with PCV and six six-weekly cycles with lomustine and temozolomide (CETEG) (n = 182 patients per group accrued over 4 years) thereby delaying radiotherapy and adding the chemoradiotherapy concept at progression after initial radiation-free chemotherapy, allowing for effective salvage treatment and delaying potentially deleterious side effects. QOS represents a new concept and is defined as OS without functional and/or cognitive and/or quality of life deterioration regardless of whether tumour progression or toxicity is the main cause. The primary objective is to show superiority of an initial CETEG treatment followed by partial brain radiotherapy (RT) plus PCV (RT-PCV) at progression over partial brain radiotherapy (RT) followed by procarbazine, lomustine, and vincristine (PCV) chemotherapy (RT-PCV) and best investigators choice (BIC) at progression for sustained qOS. An event concerning a sustained qOS is then defined as a functional and/or cognitive and/or quality of life deterioration after completion of primary therapy on two consecutive study visits with an interval of 3 months, tolerating a deviation of at most 1 month. Assessments are done with a 3-monthly MRI, assessment of the NANO scale, HRQoL, and KPS, and annual cognitive testing. Secondary objectives are evaluation and comparison of the two groups regarding secondary endpoints (short-term qOS, PFS, OS, complete and partial response rate). The trial is planned to be conducted at a minimum of 18 NOA study sites in Germany. DISCUSSION: qOS represents a new concept. The present NOA trial aims at showing the superiority of CETEG plus RT-PCV over RT-PCV plus BIC as determined at the level of OS without sustained functional deterioration for all patients with oligodendroglioma diagnosed according to the most recent WHO classification. TRIAL REGISTRATION: Clinicaltrials.gov NCT05331521 . EudraCT 2018-005027-16.

Stereotactic MRI-guided radiation therapy for localized prostate cancer (SMILE): a prospective, multicentric phase-II-trial.

BACKGROUND: Normofractionated radiation regimes for definitive prostate cancer treatment usually extend over 7-8 weeks. Recently, moderate hypofractionation with doses per fraction between 2.2 and 4 Gy has been shown to be safe and feasible with oncologic non-inferiority compared to normofractionation. Radiobiologic considerations lead to the assumption that prostate cancer might benefit in particular from hypofractionation in terms of tumor control and toxicity. First data related to ultrahypofractionation demonstrate that the overall treatment time can be reduced to 5-7 fractions with single doses > 6 Gy safely, even with simultaneous focal boosting of macroscopic tumor(s). With MR-guided linear accelerators (MR-linacs) entering clinical routine, invasive fiducial implantations become unnecessary. The aim of the multicentric SMILE study is to evaluate the use of MRI-guided stereotactic radiotherapy for localized prostate cancer in 5 fractions regarding safety and feasibility. METHODS: The study is designed as a prospective, one-armed, two-stage, multi-center phase-II-trial with 68 patients planned. Low- and intermediate-risk localized prostate cancer patients will be eligible for the study as well as early high-risk patients (cT3a and/or Gleason Score ≤ 8 and/or PSA ≤ 20 ng/ml) according to d'Amico. All patients will receive definitive MRI-guided stereotactic radiation therapy with a total dose of 37.5 Gy in 5 fractions (single dose 7.5 Gy) on alternating days. A focal simultaneous integrated boost to MRI-defined tumor(s) up to 40 Gy can optionally be applied. The primary composite endpoint includes the assessment of urogenital or gastrointestinal toxicity ≥ grade 2 or treatment-related discontinuation of therapy. The use of MRI-guided radiotherapy enables online plan adaptation and intrafractional gating to ensure optimal target volume coverage and protection of organs at risk. DISCUSSION: With moderate hypofractionation being the standard in definitive radiation therapy for localized prostate cancer at many institutions, ultrahypofractionation could be the next step towards reducing treatment time without compromising oncologic outcomes and toxicities. MRI-guided radiotherapy could qualify as an advantageous tool as no invasive procedures have to precede in therapeutic workflows. Furthermore, MRI guidance combined with gating and plan adaptation might be essential in order to increase treatment effectivity and reduce toxicity at the same time.

Determinants of Post-Operative Cognitive Decline in Elderly People.

BACKGROUND: Surgery and anesthesia can result in temporary or permanent deterioration of the cognitive functions, for which causes remain unclear. OBJECTIVES: In this pilot study, we analyzed the determinants of cognitive decline following a non-emergency elective prosthesis implantation surgery for hip or knee. DESIGN: Prospective single-center study investigating psychomotor response time and changes in MoCA scores between the day before (D-1) and 2 days after (D+2) following surgery at the Lariboisière Hospital (Paris, France). PARTICIPANTS: 60 patients (71.9±7.1-year-old, 72% women) were included. MEASUREMENTS: Collected data consisted in sociodemographic data, treatments, comorbidities and the type of anesthesia (local, general or both). Furthermore, we evaluated pain and well-being before as well as after the surgery using point scales. RESULTS: Post-operative (D+2) MoCA scores were significantly lower than pre-operative ones (D-1) with a median difference of 2 pts [IQR]=4pts, (p<0.001), we found no significant difference between locoregional and general anesthesia. Pre-operative benzodiazepine or anticholinergic treatments were also associated to a drop in MoCA scores (p=0.006). Finally, the use of ketamine during anesthesia (p=0.043) and the well-being (p=0.006) evaluated before intervention, were both linked to a reduced cognitive impact. CONCLUSION: In this pilot study, we observed a post-operative short-term cognitive decline following a lower limb surgery. We also identified pre and perioperative independent factors linked to cognitive decline following surgery. In a next stage, a larger cohort should be used to confirm the impact of these factors on cognitive decline.

Betablockers do not increase efficacy of band ligation in primary prophylaxis but they improve survival in secondary prophylaxis of variceal bleeding.

BACKGROUND: Endoscopic band ligation (EBL) is used for primary (PP) and secondary prophylaxis (SP) of variceal bleeding. Current guidelines recommend combined use of non-selective beta-blockers (NSBBs) and EBL for SP, while in PP either NSBB or EBL should be used. AIM: To assess (re-)bleeding rates and mortality in cirrhotic patients receiving EBL for PP or SP for variceal bleeding. METHODS: (Re-)bleeding rates and mortality were retrospectively assessed with and without concomitant NSBB therapy after first EBL in PP and SP. RESULTS: Seven hundred and sixty-six patients with oesophageal varices underwent EBL from 01/2005 to 06/2015. Among the 284 patients undergoing EBL for PP, n = 101 (35.6%) received EBL only, while n = 180 (63.4%) received EBL + NSBBs. In 482 patients on SP, n = 163 (33.8%) received EBL only, while n = 299 (62%) received EBL + NSBBs. In PP, concomitant NSBB therapy neither decreased bleeding rates (log-rank: P = 0.353) nor mortality (log-rank: P = 0.497) as compared to EBL alone. In SP, similar re-bleeding rates were documented in EBL + NSBB vs EBL alone (log-rank: P = 0.247). However, EBL + NSBB resulted in a significantly lower mortality rate (log-rank: P<0.001). A decreased risk of death with EBL + NSBB in SP (hazard ratio, HR: 0.50; P<0.001) but not of rebleeding, transplantation or further decompensation was confirmed by competing risk analysis. Overall NSBB intake reduced 6-months mortality (HR: 0.53, P = 0.008) in SP, which was most pronounced in patients without severe/refractory ascites (HR: 0.37; P = 0.001) but not observed in patients with severe/refractory ascites (HR: 0.80; P = 0.567). CONCLUSIONS: EBL alone seems sufficient for PP of variceal bleeding. In SP, the addition of NSBB to EBL was associated with an improved survival within the first 6 months after EBL.

Effects of resistance exercise in prostate cancer patients: a meta-analysis.

PURPOSE: The aim of the present meta-analysis was to quantify effects of resistance exercise (RE) on physical performance and function, body composition, health-related quality of life (HRQoL), and fatigue in patients with prostate cancer. METHODS: Trial data were obtained from the databases PubMed, MEDLINE, EMBASE, SCOPUS, and the Cochrane Library as of inception to 31st of December 2016. Thirty-two trials with 1199 patients were included. Results that were measured by using the same assessment method in five or more of the original studies were pooled in a meta-analysis. RESULTS: Pooled studies showed significant improvements of muscular strength in the upper and lower body (95% CI [2.52, 7.97] kg; p < 0.001 and 95% CI [10.51, 45.88] kg; p = 0.008, respectively) after RE. Furthermore, significant improvements were seen for body composition (body fat percentage 95% CI [-0.79, -0.53] %; p < 0.001; lean body mass 95% CI [0.15, 1.84] %; p = 0.028; trunk fat mass 95% CI [-0.73, -0.08] kg; p = 0.024). Additionally, the improvement of the 400-m walk time was significant (95% CI [-21.55, -14.65] s; p < 0.001). Concerning fatigue and HRQoL, there were not sufficient data for analysis. CONCLUSIONS: RE seems to be a promising approach in order to counteract loss of muscle mass, muscle strength, and physical performance in patients suffering from prostate cancer and its treatment-related side effects. RE should play part in interdisciplinary cancer rehabilitation and care of this patient group. Nevertheless, further research should investigate RE further to determine which protocols are the most pragmatic, yet yielding best patient outcomes.

Structure-function integrity of the adult hippocampus depends on the transcription factor Bcl11b/Ctip2.

The dentate gyrus is one of the only two brain regions where adult neurogenesis occurs. Throughout life, cells of the neuronal stem cell niche undergo proliferation, differentiation and integration into the hippocampal neural circuitry. Ongoing adult neurogenesis is a prerequisite for the maintenance of adult hippocampal functionality. Bcl11b, a zinc finger transcription factor, is expressed by postmitotic granule cells in the developing as well as adult dentate gyrus. We previously showed a critical role of Bcl11b for hippocampal development. Whether Bcl11b is also required for adult hippocampal functions has not been investigated. Using a tetracycline-dependent inducible mouse model under the control of the forebrain-specific CaMKIIα promoter, we show here that the adult expression of Bcl11b is essential for survival, differentiation and functional integration of adult-born granule cell neurons. In addition, Bcl11b is required for survival of pre-existing mature neurons. Consequently, loss of Bcl11b expression selectively in the adult hippocampus results in impaired spatial working memory. Together, our data uncover for the first time a specific role of Bcl11b in adult hippocampal neurogenesis and function.

[Therapeutic education of total laryngectomy patients: Influence of social factors].

Current health policies promote patient education, parti­cu­lar­ly in oncology. Therapeutic education program must be tailo­red to the characteristics, needs and expectations of the population. In the ENT Department of Head and Neck Surgery, Larrey Hospital in Toulouse, a therapeutic education program for patient with total laryngectomy has been experienced since 2011. But its propagation remains difficult. The aim of this study is to determine if social factors are nfluencing the parti­cipation of the laryngectomized population in the program. The brochure explaining this program and a registration form coupled with a survey questionnaire were distributed to the regio­nal population of patient with total laryngectomy. After two months of investigation we collected 42 responses. It is clear from their analysis that social factors underlie partici­pa­tion, particularly educational level, available financial resources level and the socio-professional group.

Prevalence and risk factors for allergic rhinitis in two resource-limited settings in Peru with disparate degrees of urbanization.

BACKGROUND: Allergic rhinitis is a disease with a high global disease burden, but risk factors that contribute to this condition are not well understood. OBJECTIVE: To assess the prevalence and risk factors of allergic rhinitis in two Peruvian populations with disparate degrees of urbanization. METHODS: We conducted a population-based, cross-sectional study on 1441 children aged 13-15 years at enrollment (mean age 14.9 years, 51% boys) to investigate the prevalence of allergic disease. We used a standardized, Spanish validated questionnaire to determine the prevalence of allergic rhinitis and asked about sociodemographics and family history of allergies. Children also underwent spirometry, exhaled nitric oxide, allergy skin testing to 10 common household allergens and provided a blood sample for measurement of 25OH vitamin D and total serum IgE. RESULTS: Overall prevalence of allergic rhinitis was 18% (95% CI 16% to 20%). When stratified by site, the prevalence of allergic rhinitis was 23% Lima vs. 13% in Tumbes (P < 0.001); however, this difference was no longer significant after controlling for subject-specific factors (P = 0.95). There was a strong association with other allergic diseases: 53% of children with asthma had allergic rhinitis vs. 15% in those without asthma (P < 0.001) and 42% of children with eczema vs. 17% of those without eczema (P < 0.001). Important risk factors for allergic rhinitis were parental rhinitis (adjusted OR = 3.0, 95% CI 1.9-4.7 for 1 parent and adjusted OR = 4.4, 95% CI 1.5-13.7 for 2 parents); allergic sensitization to common household aeroallergens (1.6, 1.1-2.3); being overweight (1.5, 1.0-2.3); exhaled nitric oxide ≥ 20 ppb (1.9, 1.3-2.7); and total serum IgE ≥ 95th percentile (2.4, 1.2-4.8). Population attributable risk of important factors for allergic rhinitis were 25% for high exhaled nitric oxide, 22% for allergic sensitization to common household aeroallergens, 22% for paternal rhinitis, 10% for being overweight and 7% for an elevated total serum IgE. CONCLUSION AND CLINICAL RELEVANCE: Allergic rhinitis was prevalent in both settings, and important risk factors include elevated exhaled nitric oxide, allergic sensitization to common household aeroallergens, parental rhinitis, being overweight and high total serum IgE. When considering subject-specific factors, the difference in prevalence between the urban and rural settings became non-important.

25-hydroxy vitamin D levels are associated with childhood asthma in a population-based study in Peru.

BACKGROUND: Vitamin D deficiency may be associated with an increased risk of asthma. OBJECTIVE: We studied the association between 25-hydroxy (25-OH) vitamin D deficiency and asthma prevalence in two Peruvian populations close to the equator but with disparate degrees of urbanization. METHODS: We conducted a population-based study in 1441 children in two communities in Peru, of which 1134 (79%) provided a blood sample for 25-OH vitamin D analysis. RESULTS: In these 1134 children, mean age was 14.8 years; 52% were boys; asthma and atopy prevalence was 12% in Lima vs. 3% in Tumbes (P < 0.001) and 59% in Lima vs. 41% in Tumbes (P < 0.001), respectively; and, mean 25-OH vitamin D level was 20.8 ng/mL in Lima vs. 30.1 ng/mL in Tumbes (P < 0.001). Prevalence of 25-OH vitamin D deficiency (< 20 ng/mL) was 47% in Lima vs. 7% in Tumbes (P < 0.001). In multi-variable logistic regression, we found that lower 25-OH vitamin D levels were associated with an increased odds of asthma (OR = 1.7 per each 10 ng/mL decrease in 25-OH vitamin D levels, 95% CI 1.2-2.6; P < 0.01). In stratified analyses, the association between lower 25-OH vitamin D levels and asthma was limited to children with atopy (OR = 2.2, 95% CI 1.3-3.6) and not in those without atopy (OR = 0.9, 95% CI 0.5-2.0). We did not find associations between 25-OH vitamin D levels and other clinical biomarkers for asthma, including exhaled nitric oxide, total serum IgE and pulmonary function. CONCLUSION AND CLINICAL RELEVANCE: Both asthma and 25-OH vitamin D deficiency were common among children living in Lima (latitude = 12.0 °S) but not among those in Tumbes (3.6 °S). The relationship between 25-OH vitamin D deficiency and asthma was similar in both sites and was limited among children with atopy. Future supplementation trials may need to consider stratification by atopy at the time of design.

Telemonitoring of patients with Parkinson's disease using inertia sensors.

BACKGROUND: Medical treatment in patients suffering from Parkinson's disease is very difficult as dose-finding is mainly based on selective and subjective impressions by the physician. OBJECTIVES: To allow for the objective evaluation of patients' symptoms required for optimal dosefinding, a telemonitoring system tracks the motion of patients in their surroundings. The system focuses on providing interoperability and usability in order to ensure high acceptance. METHODS: Patients wear inertia sensors and perform standardized motor tasks. Data are recorded, processed and then presented to the physician in a 3D animated form. In addition, the same data is rated based on the UPDRS score. Interoperability is realized by developing the system in compliance with the recommendations of the Continua Health Alliance. Detailed requirements analysis and continuous collaboration with respective user groups help to achieve high usability. RESULTS: A sensor platform was developed that is capable of measuring acceleration and angular rate of motions as well as the absolute orientation of the device itself through an included compass sensor. The system architecture was designed and required infrastructure, and essential parts of the communication between the system components were implemented following Continua guidelines. Moreover, preliminary data analysis based on three-dimensional acceleration and angular rate data could be established. CONCLUSION: A prototype system for the telemonitoring of Parkinson's disease patients was successfully developed. The developed sensor platform fully satisfies the needs of monitoring patients of Parkinson's disease and is comparable to other sensor platforms, although these sensor platforms have yet to be tested rigorously against each other. Suitable approaches to provide interoperability and usability were identified and realized and remain to be tested in the field.

Molecular requirements for inhibition of the chemokine receptor CCR8--probe-dependent allosteric interactions.

BACKGROUND AND PURPOSE: Here we present a novel series of CCR8 antagonists based on a naphthalene-sulfonamide structure. This structure differs from the predominant pharmacophore for most small-molecule CC-chemokine receptor antagonists, which in fact activate CCR8, suggesting that CCR8 inhibition requires alternative structural probes. EXPERIMENTAL APPROACH: The compounds were tested as inverse agonists and as antagonists against CCL1-induced activity in Gα(i) signalling and chemotaxis. Furthermore, they were assessed by heterologous competition binding against two radiolabelled receptor ligands: the endogenous agonist CCL1 and the virus-encoded antagonist MC148. KEY RESULTS: All compounds were highly potent inverse agonists with EC(50) values from 1.7 to 23 nM. Their potencies as antagonists were more widely spread (EC(50) values from 5.9 to 1572 nM). Some compounds were balanced antagonists/inverse agonists whereas others were predominantly inverse agonists with >100-fold lower potency as antagonists. A correspondingly broad range of affinities, which followed the antagonist potencies, was disclosed by competition with [(125)I]-CCL1 (K(i) 3.4-842 nM), whereas the affinities measured against [(125)I]-MC148 were less widely spread (K(i) 0.37-27 nM), and matched the inverse agonist potencies. CONCLUSION AND IMPLICATIONS: Despite highly potent and direct effects as inverse agonists, competition-binding experiments against radiolabelled agonist and tests for antagonism revealed a probe-dependent allosteric effect of these compounds. Thus, minor chemical changes affected the ability to modify chemokine binding and action, and divided the compounds into two groups: predominantly inverse agonists and balanced antagonists/inverse agonists. These studies have important implications for the design of new inverse agonists with or without antagonist properties.

Long-term effects of a binary mixture of perfluorooctane sulfonate (PFOS) and bisphenol A (BPA) in zebrafish (Danio rerio).

Previous in vitro studies have reported the potential of perfluorooctane sulfonate (PFOS) to increase the toxicity of other compounds. Given the complex nature of mixtures of environmental pollutants in aquatic systems together with the persistent and bioaccumulative properties of PFOS, this study aimed at evaluating the long-term effects and toxicity-increasing behavior of PFOS in vivo using the zebrafish (Danio rerio). Fish were maintained in flow-through conditions and exposed to single and binary mixtures of PFOS and the endocrine disruptor bisphenol A (BPA) at nominal concentrations of 0.6, 100 and 300 µg/L and 10, 200 and 400 µg/L, respectively. F1 and F2 generations were evaluated from 0 to 180 days post-fertilization (dpf) and F3 generation was evaluated from 0 to 14 dpf. Survival was documented in all generations, whereas growth, fecundity, fertilization rate, histological alterations (in liver, thyroid and gonads) and vitellogenin (Vtg) induction in males were evaluated for F1 and F2 generations. Data for growth were collected at 30, 90 and 180 dpf and data for histological evaluations and Vtg induction were analyzed at 90 and 180 dpf. No significant effects on survival were seen in the F1 generation in any treatment following 180 d exposure; however, in the F2 generation, 300 µg/L PFOS both alone and in combination with BPA (10, 200 and 400 µg/L) induced 100% mortality within 14 dpf. PFOS (0.6 and 300 µg/L) did not increase the Vtg-inducing potential of BPA (10, 200 and 400 µg/L) in a binary mixture. In contrast, binary mixtures with 300 µg/L PFOS suppressed the Vtg levels in F1 males at 90 dpf when compared to single BPA exposures. Whereas the lowest tested PFOS concentration (0.6 µg/L) showed an estrogenic potential in terms of significant Vtg induction, Vtg levels were generally found to decrease with increasing PFOS-exposure in both F1 and F2 generations. In F1 generation, BPA-exposure was found to increase Vtg levels in a concentration-dependent manner. Histological analyses of F1 and F2 fish revealed hepatocellular vacuolization, predominantly in males, following PFOS-exposure both alone and in combination with BPA. Hepatotoxicity by PFOS might explain the suppressed Vtg response seen in PFOS-exposed F1 and F2 males. PFOS-exposed fish also showed granulomas, mainly in the liver. Given previous reports of the immunosuppressive potential of PFOS, the granulomas could be a consequence of a PFOS-induced reduction of the immune response potential. In conclusion, the hypothesis that the presence of PFOS increases the endocrine potential of BPA could not be confirmed in zebrafish. Adverse effects on liver structure and survival were only seen at concentrations well above ecologically relevant concentrations; however, the decline in survival rates following PFOS-exposure seen over generations again documents the importance of long-term studies for the investigation of persistent environmental pollutants.

Preliminary clinical study using a multiplex real-time PCR test for the detection of bacterial and fungal DNA directly in blood.

Early diagnosis of sepsis, rapid identification of the causative pathogen(s) and prompt initiation of appropriate antibiotic treatment have a combined impact on mortality due to sepsis. In this observational study, a new DNA-based system (LightCycler SeptiFast (LC-SF) test; Roche Diagnostics) allowing detection of 16 pathogens at the species level and four groups of pathogens at the genus level has been evaluated and compared with conventional blood cultures (BCs). One hundred BC and LC-SF results were obtained for 72 patients admitted to the intensive-care unit over a 6-month period for suspected sepsis. Microbiological data were compared with other biological parameters and with clinical data. The positivity rate of BCs for bacteraemia/fungaemia was 10%, whereas the LC-SF test allowed detection of DNA in 15% of cases. The LC-SF performance, based on its clinical relevance, was as follows: sensitivity, 78%; specificity, 99%; positive predictive value, 93%; and negative predictive value, 95%. Management was changed for four of eight (50%) of the patients because organisms were detected by the LC-SF test but not by BC. LC-SF results were obtained in 7-15 h, in contrast to the 24-72 h required for BC. According to the LC-SF results, initial therapy was inadequate in eight patients, and antibiotic treatment was changed. Our results suggest that the LC-SF test may be a valuable complementary tool in the management of patients with clinically suspected sepsis.

[Fast-track concepts in the perioperative management of patients undergoing radical cystectomy and urinary diversion: review of the literature and research results]. / Fast-track-Konzepte im perioperativen Management bei Zystektomie und Harnableitung: Literaturübersicht und eigene Ergebnisse.

Fast-track (FT) protocols in visceral surgery incorporate innovative aspects of analgesia, bowel preparation, enteralization, and drainage management. In elective colorectal surgery, these concepts are the standard of care. In uro-oncological surgery, however, they are used very reluctantly, although the available data show that early nasogastric tube removal and enteralization and the omission of preoperative bowel preparation have positive effects on convalescence and hospital stay. The work presented here was initiated to compare traditional and FT management in a randomized fashion, focusing on complication rates and the course of enteralization as outcome measures. Complication rates, especially of bowel-associated complications, were not increased in the FT group. The postoperative stay on the intermediate care unit was significantly shorter in the FT cohort, and enteralization was completed significantly earlier. FT management is not associated with an increased risk of major complications in urinary diversion surgery. Controlled clinical trials are needed to further evaluate important aspects of a standardized perioperative plan of care (including antibiotic regimen and earlier removal of ureteral and neobladder catheters).

Antioxidants used in skin care formulations.

The formation of free radicals is a widely accepted pivotal mechanism leading to skin aging. Free radicals are highly reactive molecules with unpaired electrons that can directly damage various cellular structural membranes, lipids, proteins, and DNA. The damaging effects of these reactive oxygen species are induced internally during normal metabolism and externally through various oxidative stresses. The production of free radicals increases with age, while the endogenous defense mechanisms that counter them decrease. This imbalance leads to the progressive damage of cellular structures, and thus, results in accelerated aging. Antioxidants are substances that can provide protection from endogenous and exogenous oxidative stresses by scavenging free radicals. Topical antioxidants are available in multivariate combinations through over-the-counter skin care products that are aimed at preventing the clinical signs of photoaging.

Reasons for declining computerized insulin protocol recommendations: application of a framework.

Clinical decision support systems (CDS) can interpret detailed treatment protocols for ICU care providers. In open-loop systems, clinicians can decline protocol recommendations. We capture their reasons for declining as part of ongoing, iterative protocol validation and refinement processes. Even though our protocol was well-accepted by clinicians overall, noncompliance patterns revealed potential protocol improvement targets, and suggested ways to reduce barriers impeding software use. We applied Rita Kukafka and colleagues' (2003) IT implementation framework to identify and categorize reasons documented by ICU nurses when declining recommendations from an insulin-titration protocol. Two methods were used to operationalize the framework: reasons for declining recommendations from actual software use, and a nurse questionnaire. Applying the framework exposed limitations of our data sources, and suggested ways to address those limitations; and facilitated our analyses and interpretations.

Recurrent posttraumatic meningitis due to nontypable Haemophilus influenzae: case report and review of the literature.

We report a case of relapsing Haemophilus influenzae meningitis in a boy at the age of nearly 3 years and 4.2 years who had been successfully vaccinated against H. influenzae serotype b (Hib). The pathogen was a nonencapsulated (nontypable) H. influenzae strain of biotypes III and VI, respectively. A rhinobasal impalement injury with development of a posttraumatic encephalocele is considered to be the predisposing condition. Review of the literature reveals that in patients systemically infected by nonencapsulated H. influenzae strains predisposing factors such as cerebrospinal fluid-shunts, implants and traumas are often found. To obtain further information on potential new disease patterns H. influenzae isolates from cerebrospinal fluid should be examined for capsule production and, if relevant, further characterized by capsular typing.

Skin ageing and its treatment.

The effects of chronic sun exposure on skin are readily apparent when skin not typically exposed to the sun and skin regularly exposed to the sun are compared. While the sun is not the only aetiological factor in the dynamic process of skin ageing, it is the primary exogenous cause among several internal and environmental elements. Thus, photo-ageing, the main focus of this article, is a subset of extrinsic skin ageing. The influence of the sun in extrinsic skin ageing, as well as its role in potentially altering the normal course of intrinsic (also known as natural or cellular) ageing, is discussed. Telomeres, the specialized structures found at the ends of chromosomes, are believed to be integral to cellular ageing as well as in the development of cancer. The ageing process, both intrinsic and extrinsic, is also believed to be influenced by the formation of free radicals, also known as reactive oxygen species. The loss of collagen is considered the characteristic histological finding in aged skin. Wrinkling and pigmentary changes are directly associated with photo-ageing and are considered its most salient cutaneous manifestations. Such photodamage represents the cutaneous signs of premature ageing. In addition, deleterious consequences of chronic sun exposure, specifically various forms of photo-induced skin cancer, are also linked to acute and chronic sun exposure. The only known strategies aimed at preventing photo-ageing include sun avoidance, using sunscreens to block or reduce skin exposure to UV radiation, using retinoids to inhibit collagenase synthesis and to promote collagen production, and using anti-oxidants, particularly in combination, to reduce and neutralize free radicals.