Frequency and associated symptoms of isthmoceles in women 6 months after caesarean section: a prospective cohort study.

PURPOSE: The purpose of this study was to determine the frequency of detection of isthmoceles by ultrasound 6 months after caesarean section (CS) and which symptoms associated with isthmocele formation occur after CS. Subsequently, it was determined how often the ultrasound finding "isthmocele" coincided with the presence of complaints. METHODS: A prospective multicentre cohort study was conducted with 546 patients from four obstetric centres in Berlin, who gave birth by primary or secondary CS from October 2019 to June 2020. 461 participants were questioned on symptoms 3 months after CS; 329 participants were included in the final follow-up 6 months after CS. The presence of isthmoceles was determined by transvaginal sonography (TVS) 6 months after CS, while symptoms were identified by questionnaire. RESULTS: Of the 329 women, 146 (44.4%) displayed an isthmocele in the TVS. There was no statistically significant difference in the manifestation of symptoms between the two groups of women with and without isthmocele; however, when expressed on a scale from 1 to 10 the intensity of both scar pain and lower abdominal pain was significantly higher in the set of women that had shown to have developed an isthmocele (p = 0.014 and p = 0.031, respectively). CONCLUSION: The prevalence of isthmoceles 6 months after CS was 44.4%. Additionally, scar pain and lower abdominal pain were more pronounced when an isthmocele was also observed in the TVS. TRIAL REGISTRATION: Trial registration number DRKS00024977. Date of registration 17.06.2021, retrospectively registered.

Determine the impact of a structured pharmacist-led medication review - a controlled intervention study to optimise medication safety for residents in long-term care facilities.

BACKGROUND: Medication reviews contribute to protecting long-term care (LTC) residents from drug related problems (DRPs). However, few controlled studies have examined the impact on patient-relevant outcomes so far. OBJECTIVE: We examined the impact of a one-time, pharmacist-led medication review on medication changes (primary endpoint) including discontinued medication, the number of chronic medications, hospital admissions, falls, and deaths (secondary endpoints). METHODS: A prospective, controlled intervention study was performed in three LTC facilities. In the intervention group (IG), after performing a medication review, a pharmacist gave recommendations for resolving DRPs to physicians, nurses and community pharmacists. The control group (CG) received usual care without a medication review. (i) We assessed the number of medication changes and the secondary endpoints in both groups before (t0) and after (t1, t2) the intervention. (ii) Additionally, the medication review was evaluated in the IG with regard to identified DRPs, the healthcare professional's feedback on the forwarded pharmacist recommendations and whether DRPs were finally resolved. RESULTS: 107 (IG) and 104 (CG) residents were enrolled. (i) More medication changes were identified in the IG than in the CG at t1 (p = 0.001). However, no significant difference was identified at t2 (p = 0.680). Mainly, medication was discontinued in those medication changes. Chronic medications increased in the CG (p = 0.005) at t2 while hospital admissions, falls, and deaths showed no differences. (ii) Overall, 1252 DRPs (median: 10; minimum-maximum: 2-39) were identified. Recommendations for 82% of relevant DRPs were forwarded to healthcare professionals, of which 61% were accepted or clarified. 22% were not accepted, 12% required further review and 6% remained without feedback. 51% of forwarded DRPs were finally resolved. CONCLUSIONS: We found more medication changes in the IG compared to controls. Mostly, medication was discontinued. This suggests that our intervention was successful in discontinuing unnecessary medication. Other clinical outcomes such as falls, hospitalisations, and deaths were not improved due to the one-time intervention. The medication review further identified a high prevalence of DRPs in the IG, half of which were finally resolved. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00026120 ( www.drks.de , retrospectively registered 07/09/2021).

Why does a point of care guided transfusion algorithm not improve blood loss and transfusion practice in patients undergoing high-risk cardiac surgery? A prospective randomized controlled pilot study.

BACKGROUND: Adult cardiac surgery is often complicated by elevated blood losses that account for elevated transfusion requirements. Perioperative bleeding and transfusion of blood products are major risk factors for morbidity and mortality. Timely diagnostic and goal-directed therapies aim at the reduction of bleeding and need for allogeneic transfusions. METHODS: Single-centre, prospective, randomized trial assessing blood loss and transfusion requirements of 26 adult patients undergoing elective cardiac surgery at high risk for perioperative bleeding. Primary endpoint was blood loss at 24 h postoperatively. Random assignment to intra- and postoperative haemostatic management following either an algorithm based on conventional coagulation assays (conventional group: platelet count, aPTT, PT, fibrinogen) or based on point-of-care (PoC-group) monitoring, i.e. activated rotational thromboelastometry (ROTEM®) combined with multiple aggregometry (Multiplate®). Differences between groups were analysed using nonparametric tests for independent samples. RESULTS: The study was terminated after interim analysis (n = 26). Chest tube drainage volume was 360 ml (IQR 229-599 ml) in the conventional group, and 380 ml (IQR 310-590 ml) in the PoC-group (p = 0.767) after 24 h. Basic patient characteristics, results of PoC coagulation assays, and transfusion requirements of red blood cells and fresh frozen plasma did not differ between groups. Coagulation results were comparable. Platelets were transfused in the PoC group only. CONCLUSION: Blood loss via chest tube drainage and transfusion amounts were not different comparing PoC- and central lab-driven transfusion algorithms in subjects that underwent high-risk cardiac surgery. Routine PoC coagulation diagnostics do not seem to be beneficial when actual blood loss is low. High risk procedures might not suffice as a sole risk factor for increased blood loss. TRIAL REGISTRATION: NCT01402739 , Date of registration July 26, 2011.

Associations of postoperative mortality with the time of day, week and year.

Studies that have investigated circadian, weekday and seasonal variation in postoperative mortality have been relatively small or have been for scheduled surgery. We retrospectively tested a large mixed surgical cohort from a German tertiary care university hospital for the presence of cyclical variation in all-cause in-hospital mortality after operations performed between 2006 and 2013. We analysed mortality rates after 247,475 operations, adjusted for age, sex, comorbidities, location, urgency and duration of the surgery, and intra-operative blood transfusions. The mortality odds ratio (95%CI) after operations started in the morning (08:00-11:00) were lowest, 0.73 (0.66-0.80), p < 0.001 and highest for operations started in the afternoon (13:00-17:00), 1.29 (1.18-1.40), p < 0.001. Mortality at the weekend was the same as during the week. There was no seasonal variation in mortality, p = 0.12. However, the interference of four-yearly and ten-monthly cycle amplitudes resulted in higher mortality odds ratio (95%CI) in winter 2008-2009, 1.41 (1.18-1.69), p < 0.001, and lower mortality in spring 2011 and 2012, 0.70 (0.56-0.85) and 0.67 (0.53-0.85), p < 0.001 and p = 0.001, respectively. The ability to predict cyclical phenomena would facilitate the design of interventional studies, aimed at reducing mortality following surgery in the afternoon and when cycles interfere constructively.

The new agreement of the international RIGA consensus conference on nasal airway function tests.

The report reflects an agreement based on the consensus conference of the International Standardization Committee on the Objective Assessment of the Nasal Airway in Riga, 2nd Nov. 2016. The aim of the conference was to address the existing nasal airway function tests and to take into account physical, mathematical and technical correctness as a base of international standardization as well as the requirements of the Council Directive 93/42/EEC of 14 June 1993 concerning medical devices. Rhinomanometry, acoustic rhinometry, peak nasal inspiratory flow, Odiosoft-Rhino, optical rhinometry, 24-h measurements, computational fluid dynamics, nasometry and the mirrow test were evaluated for important diagnostic criteria, which are the precision of the equipment including calibration and the software applied; validity with sensitivity, specificity, positive and negative predictive values, reliability with intra-individual and inter-individual reproducibility and responsiveness in clinical studies. For rhinomanometry, the logarithmic effective resistance was set as the parameter of high diagnostic relevance. In acoustic rhinometry, the area of interest for the minimal cross-sectional area will need further standardization. Peak nasal inspiratory flow is a reproducible and fast test, which showed a high range of mean values in different studies. The state of the art with computational fluid dynamics for the simulation of the airway still depends on high performance computing hardware and will, after standardization of the software and both the software and hardware for imaging protocols, certainly deliver a better understanding of the nasal airway flux.

Risk factors for 30-day complications after cancer surgery in geriatric patients: a secondary analysis.

BACKGROUND: The aim was to analyse the association between severity of complications up to 30 days after surgery and pre-operative nutritional and physical performance parameters. METHODS: The participants were a subsample of the previously published PERATECS study (ClinicalTrials.gov: NCT01278537) and included 517 onco-geriatric patients aged ≥ 65 years, undergoing thoracoabdominal, gynaecological, or urological surgery. Post-operative complications were classified according to the Clavien Classification System (CCS). Independent risk factors related to the severity of complications, defined as major complications (CCS IIIa-V) and graded complications (CCS grade 0-V), were analysed using logistic and ordinal regression, respectively. RESULTS: In total, 132 patients suffered major post-operative complications. The development of major post-operative complications was independently associated with body mass index (BMI) < 20 kg/m2 , hypoalbuminaemia (< 30 g/l), longer duration of surgery, and specific tumour sites (upper gastrointestinal, gynaecological, colorectal) (all P < 0.05). Higher-grade complications were predicted by Timed Up and Go (TUG) > 20 s, hypoalbuminaemia (< 30 g/l), higher American Society of Anesthesiologists (ASA) status III-IV, longer duration of surgery (> 165 min), and specific tumour sites (upper gastrointestinal, gynaecological) (all P < 0.05). Mini Nutritional Assessment (MNA) scores and weight loss were not independent risk factors for the severity of complications. CONCLUSIONS: Nutritional and physical performance risk factors that predicted the severity of complications differed between major and higher-grade post-operative complications, but hypoalbuminaemia independently predicted both. The results support the need for pre-operative risk screening. Due to the explorative nature of the study, further research is required in larger cohorts to corroborate these findings.

Feasibility of noise reduction by a modification in ICU environment.

Noise is a proven cause of wakefulness and qualitative sleep disturbance in critically ill patients. A sound pressure level reduction can improve sleep quality, but there are no studies showing the feasibility of such a noise reduction in the intensive care unit (ICU) setting. Considering all available evidence, we redesigned two ICU rooms with the aim of investigating the physiological and clinical impact of a healing environment, including a noise reduction and day-night variations of sound level. Within an experimental design, we recorded 96 h of sound-pressure levels in standard ICU rooms and the modified ICU rooms. In addition, we performed a sound source observation by human observers. Our results show that we reduced A-weighted equivalent sound pressure levels and maximum sound pressure levels with our architectural interventions. During night-time, the modification led to a significant decrease in 50 dB threshold overruns from 65.5% to 39.9% (door side) and from 50% to 10.5% (window side). Sound peaks of more than 60 decibels were significantly reduced from 62.0% to 26.7% (door side) and 59.3% to 30.3% (window side). Time-series analysis of linear trends revealed a significantly more distinct day-night pattern in the modified rooms with lower sound levels during night-times. Observed sound sources during night revealed four times as many talking events in the standard room compared to the modified room. In summary, we show that it is feasible to reduce sound pressure levels using architectural modifications.

Dynamic muscle O2 saturation response is impaired during major non-cardiac surgery despite goal-directed haemodynamic therapy.

BACKGROUND: Near-infrared spectroscopy combined with a vascular occlusion test (VOT) could indicate an impairment of microvascular reactivity (MVR) in septic patients by detecting changes in dynamic variables of muscle O2 saturation (StO2). However, in the perioperative context the consequences of surgical trauma on dynamic variables of muscle StO2 as indicators of MVR are still unknown. METHODS: This study is a sub-analysis of a randomised controlled trial in patients with metastatic primary ovarian cancer undergoing debulking surgery, during which a goal-directed haemodynamic algorithm was applied using oesophageal Doppler. During a 3 min VOT, near-infrared spectroscopy was used to assess dynamic variables arising from changes in muscle StO2. RESULTS: At the beginning of surgery, values of desaturation and recovery slope were comparable to values obtained in healthy volunteers. During the course of surgery, both desaturation and recovery slope showed a gradual decrease. Concomitantly, the study population underwent a transition to a surgically induced systemic inflammatory response state shown by a gradual increase in norepinephrine administration, heart rate, and Interleukin-6, with a peak immediately after the end of surgery. Higher rates of norepinephrine and a higher heart rate were related to a faster decline in StO2 during vascular occlusion. CONCLUSIONS: Using near-infrared spectroscopy combined with a VOT during surgery showed a gradual deterioration of MVR in patients treated with optimal haemodynamic care. The deterioration of MVR was accompanied by the transition to a surgically induced systemic inflammatory response state.

A Rare Case of Isolated Cerebral Sarcoidosis Presenting as Suprasellar Mass Lesion with Salt-Wasting Hypopituitarism.

Background Sarcoidosis is a systemic disorder of unknown origin characterized by noncaseating granulomas. Clinical symptoms due to central nervous system (CNS) involvement occur in 5 to 7% of all cases; subclinical involvement is more frequent. Sole CNS involvement is very rare. Case Report A 25-year-old man presented with increasing polyuria and polydipsia over 8 weeks. Magnetic resonance imaging (MRI) revealed a supra- and infra-chiasmatic pre-thalamic mass lesion 1.0 × 1.4 × 1.4cm in diameter. Microsurgical biopsy verified a necrotizing noncaseating epithelioid cell tumor indicative for neurosarcoidosis. All symptoms dissolved within 3 months under stringent corticoid therapy. Conclusion Intracranial mass lesions as the primary and only manifestation of neuronal sarcoidosis are rare. Because conservative treatment is safe and effective, surgery is limited to biopsy and the alleviation of pressure-related symptoms to preserve neurologic function.

Feasibility and influence of hTEE monitoring on postoperative management in cardiac surgery patients.

Monoplane hemodynamic TEE (hTEE) monitoring (ImaCor(®) ClariTEE(®)) might be a useful alternative to continuously evaluate cardiovascular function and we aimed to investigate the feasibility and influence of hTEE monitoring on postoperative management in cardiac surgery patients. After IRB approval we reviewed the electronic data of cardiac surgery patients admitted to our intensive care between 01/01/2012 and 30/06/2013 in a case-controlled matched-pairs design. Patients were eligible for the study when they presented a sustained hemodynamic instability postoperatively with the clinical need of an extended hemodynamic monitoring: (a) hTEE (hTEE group, n = 18), or (b) transpulmonary thermodilution (control group, n = 18). hTEE was performed by ICU residents after receiving an approximately 6-h hTEE training session. For hTEE guided hemodynamic optimization an institutional algorithm was used. The hTEE probe was blindly inserted at the first attempt in all patients and image quality was at least judged to be adequate. The frequency of hemodynamic examinations was higher (ten complete hTEE examinations every 2.6 h) in contrast to the control group (one examination every 8 h). hTEE findings, including five unexpected right heart failure and one pericardial tamponade, led to a change of current therapy in 89% of patients. The cumulative dose of epinephrine was significantly reduced (p = 0.034) and levosimendan administration was significantly increased (p = 0.047) in the hTEE group. hTEE was non-inferior to the control group in guiding norepinephrine treatment (p = 0.038). hTEE monitoring performed by ICU residents was feasible and beneficially influenced the postoperative management of cardiac surgery patients.

[Ocular blood flow regulation in glaucoma - examination with the ocular pressure flow analyzer (OPFA)]. / Okuläre Durchblutungsregulation beim Glaukom. Untersuchungen mit dem Ocular Pressure Flow Analyzer (OPFA).

BACKGROUND: The results of studies of ocular blood flow (BF) regulation of patients with primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG) and ocular hypertension (OH) are presented. METHODS AND PATIENTS: Examinations were carried out with the "OPFA", a newly developed ocular pressure flow analyzer (producer: tpm Lüneburg) on 92 patients with newly diagnosed glaucomas, among whom 48 patients had POAG, 22 NTG and 22 OH, and compared with age-matched groups of healthy subjects. The OPFA uses pneumatic coupling through special scleral suction cups to record ocular pulses with highly sensitive transducers and a suction pump for simultaneously increasing intraocular pressure (IOP). Following local drop anaesthesia on both eyes, IOP is artificially raised to suprasystolic values. While continuously lowering IOP, the ocular pulse is then recorded with increasing ocular perfusion pressure. We obtain the relative ocular pulse blood volume by correlating the ocular pulse amplitudes with a calibration volume of 1 µl. This enables us to collect reproducible data on intra- and inter-individual pulse blood volume (PVoc). The ocular perfusion pressure pulse blood volume curve characterizes the respective individual ocular circulation as well as systolic and diastolic ocular perfusion pressures. RESULTS: In healthy subjects, the ocular pulse blood volume remains stable over a certain range of ocular perfusion pressure (ppoc) changes. After exceeding a critical point (CP), the ocular pulse blood volume drops. We refer to the difference between the CP and IOP as the autoregulatory capacity (AC). In patients with POAG and in patients with NTG, the AC was reduced significantly compared with the groups of healthy subjects. The mean AC of patients with OH remained within the normal range. The ROC curves showed at an optimal cut-off value for POAG a sensitivity of 75.0 % and a specificity of 97.9 %, for NTG a sensitivity of 77.3 % and a specificity of 100 %. In patients with POAG and OH, the ocular arterial pressures were elevated. In patients with NTG they remained unchanged compared with the healthy subjects. The ocular perfusion pressures did not change in POAG as well as in NTG and OH. CONCLUSIONS: In patients with POAG and in patients with NTG the ocular BF regulation was impaired and detected by the OPFA device with a high level of reliability. Ocular arterial blood pressures were increased as a result of vascular regulation to keep up the ocular perfusion pressure and to maintain ocular perfusion.

Comparison of three models for sepsis patient discrimination according to PIRO: predisposition, infection, response and organ dysfunction.

BACKGROUND: Sepsis remains one of the most challenging burdens of critically ill patients. But for interventional studies significant heterogeneity remains in classifying patients. PIRO (Predisposition, Response, Infection and Organ dysfunction) has been introduced as innovative option for improved patient characterization. Aim of this study was to evaluate precision to predict hospital mortality of three different proposed PIRO classification systems. METHODS: Data were prospectively obtained data in five ICUs in a university hospital in Berlin, Germany including adult patients with sepsis. Three different scoring systems were compared using patient characteristics to classify the population according to all cause hospital mortality risk (Moreno- PIRO, Rubulotta- PIRO and Howell-PIRO). RESULTS: Two-hundred-seventy-eight sepsis patients were included and reclassified using different PIRO models. All cause hospital mortality was 16.2%. Hospital mortality increased with higher PIRO scores with odds ratios of 1.070 (95% CI 1.041-1.100) for Moreno-PIRO, 1.282 (95% CI 1.079-1.524) for Rubulotta-PIRO and 1.256 (95% CI 1.146-1.367) for Howell-PIRO. Area under the curves for Moreno-PIRO was 0.743 (95% CI: 0.687-0.793), for Rubulotta-PIRO 0.646 (95% CI: 0.587-0.702) and for Howell-PIRO 0.751 (95% CI: 0.696-0.801). Moreno-PIRO and Howell-PIRO were statistically different compared with Rubulotta-PIRO (P=0.046 and P=0.035). CONCLUSION: Proposed PIRO classifications demonstrated slight differences between models without prioritization of one approach and all seemed feasible for patient classification. Future PIRO-development is needed to straighten predisposition, infection, and especially the response category.

Fox urine exposure induces avoidance behavior in rats and activates the amygdalar olfactory cortex.

Predator odors represent a group of biologically-relevant chemosignals called kairomones. Kairomones enable prey animals to recognize potential predatory threats in their environment and to initiate appropriate defensive responses. Although the behavioral repertoire of anti-predatory responses (e.g. avoidance, freezing, risk assessment) has been investigated extensively, our knowledge about the neural network mediating these innate fear responses is rather limited. In the present study, the GABAA agonist muscimol was bilaterally injected (2.6 nmol/0.3 µl) into the amygdalar olfactory cortex (AOC), a brain area that receives massive olfactory input from both olfactory systems and is strongly interconnected with the medial hypothalamic defense circuit. Temporary inactivation of the AOC substantially disrupted avoidance behavior of rats to fox urine that is strongly avoided under control conditions (saline injections). Taken together, these results demonstrate that the AOC is critically involved in fox urine-induced fear behavior. This suggests that the AOC is part of a brain fear circuit that mediates innate fear responses toward predatory odors.

Long-term effect of computer-assisted decision support for antibiotic treatment in critically ill patients: a prospective 'before/after' cohort study.

OBJECTIVES: Antibiotic resistance has risen dramatically over the past years. For individual patients, adequate initial antibiotic therapy is essential for clinical outcome. Computer-assisted decision support systems (CDSSs) are advocated to support implementation of rational anti-infective treatment strategies based on guidelines. The aim of this study was to evaluate long-term effects after implementation of a CDSS. DESIGN: This prospective 'before/after' cohort study was conducted over four observation periods within 5 years. One preinterventional period (pre) was compared with three postinterventional periods: directly after intensive implementation efforts (post1), 2 years (post2) and 3 years (post3) after implementation. SETTING: Five anaesthesiological-managed intensive care units (ICU) (one cardiosurgical, one neurosurgical, two interdisciplinary and one intermediate care) at a university hospital. PARTICIPANTS: Adult patients with an ICU stay of >48 h were included in the analysis. 1316 patients were included in the analysis for a total of 12,965 ICU days. INTERVENTION: Implementation of a CDSS. OUTCOME MEASURES: The primary end point was percentage of days with guideline adherence during ICU treatment. Secondary end points were antibiotic-free days and all-cause mortality compared for patients with low versus high guideline adherence. MAIN RESULTS: Adherence to guidelines increased from 61% prior to implementation to 92% in post1, decreased in post2 to 76% and remained significantly higher compared with baseline in post3, with 71% (p=0.178). Additionally, antibiotic-free days increased over study periods. At all time periods, mortality for patients with low guideline adherence was higher with 12.3% versus 8% (p=0.014) and an adjusted OR of 1.56 (95% CI 1.05 to 2.31). CONCLUSIONS: Implementation of computerised regional adapted guidelines for antibiotic therapy is paralleled with improved adherence. Even without further measures, adherence stayed high for a longer period and was paralleled by reduced antibiotic exposure. Improved guideline adherence was associated with reduced ICU mortality. TRIAL REGISTRATION NUMBER: ISRCTN54598675.

Oesophageal Doppler and calibrated pulse contour analysis are not interchangeable within a goal-directed haemodynamic algorithm in major gynaecological surgery.

BACKGROUND: Evidence for the benefit of an intraoperative use of a goal-directed haemodynamic management has grown. We compared the oesophageal Doppler monitor (ODM, CardioQ-ODM™) with a calibrated pulse contour analysis (PCA, PiCCO2™) with regard to assessment of stroke volume (SV) changes after volume administration within a goal-directed haemodynamic algorithm during non-cardiac surgery. METHODS: The data were obtained prospectively in patients with metastatic ovarian carcinoma undergoing cytoreductive surgery. During surgery, fluid challenges were performed as indicated by the goal-directed haemodynamic algorithm guided by the ODM. Monitors were compared regarding precision and trending. Clinical characteristics associated with trending were studied by extended regression analysis. RESULTS: A total of 762 fluid challenges were performed in 41 patients resulting in 1524 paired measurements. The precision of ODM and PCA was 5.7% and 6.0% (P=0.80), respectively. Polar plot analysis revealed a poor trending between ODM and PCA with an angular bias of -7.1°, radial limits of agreement of -58.1° to 43.8°, and an angular concordance rate of 67.8%. Dose of norepinephrine (NE) (scaled 0.1 µg kg(-1) min(-1)) [adjusted odds ratio (OR) 0.606 (95% confidence interval, CI: 0.404-0.910); P=0.016] and changes in mean arterial pressure (MAP) to a fluid challenge (scaled 10%) [adjusted OR 0.733 (95% CI: 0.635-0.845); P<0.001] were associated with trending between ODM and PCA, whereas there was no relation to type of i.v. solution. CONCLUSIONS: Despite a similar precision, ODM and PCA were not interchangeable with regard to measuring SV changes within a goal-directed haemodynamic algorithm. A decrease in interchangeability coincided with increasing NE levels and greater changes of MAP to a fluid challenge.

Concurrent hyperfractionated accelerated radiotherapy with 5-FU and once weekly cisplatin in locally advanced head and neck cancer. The 10-year results of a prospective phase II trial.

PURPOSE: In this study, the acute toxicity and long-term outcome of a hyperfractionated accelerated chemoradiation regimen with cisplatin/5-fluorouracil (5-FU) in patients with locally advanced squamous cell carcinomas of head and neck were evaluated. PATIENTS AND METHODS: From 2000-2002, 38 patients with stage III (5.3 %) and stage IV (94.7 %) head and neck cancer were enrolled in a phase II study. Patients received hyperfractionated-accelerated radiotherapy with 72 Gy in 15 fractions of 2 Gy followed by 1.4 Gy twice daily with concurrent, continuous infusion 5-FU of 600 mg/m(2) on days 1-5 and 6 cycles of weekly cisplatin (30 mg/m(2)). Acute toxicities (CTCAEv2.0), locoregional control (LRC), metastases-free (MFS), and overall survival (OS) were analyzed and exploratively compared with the ARO 95-06 trial. RESULTS: Median follow-up was 11.4 years (95 % CI 8.6-14.2) and mean dose 71.6 Gy. Of the patients, 82 % had 6 (n = 15) or 5 (n = 16) cycles of cisplatin, 5 and 2 patients received 4 and 3 cycles, respectively. Grade 3 anemia, leukopenia, and thrombocytopenia were observed in 15.8, 15.8, and 2.6 %, respectively. Grade 3 mucositis in 50 %, grade 3 and 4 dysphagia in 55 and 13 %. The 2-, 5-, and 10-year LRC was 65, 53.6, and 48.2 %, the MFS was 77.5, 66.7, and 57.2 % and the OS 59.6, 29.2, and 15 %, respectively. CONCLUSION: Chemoradiation with 5-FU and cisplatin seems feasible and superior in terms of LRC and OS to the ARO 95-06C-HART arm at 2 years. However, this did not persist at the 5- and 10-year follow-ups.

Preoperative depression and hospital length of stay in surgical patients.

BACKGROUND: The association of depression and hospital length of stay (LOS) has rarely been examined in surgical patients outside of cardiovascular surgery. This study investigates whether clinically significant preoperative depression shows an independent association with LOS in patients from various surgical fields after adjusting for age, gender and important somatic factors. METHODS: A total of 2624 surgical patients were included in this prospective observational study. Data were collected before the preoperative anesthesiological examination within a computer-assisted psychosocial self-assessment including screening for depression (Center for Epidemiologic Studies Depression Scale, CES-D). Data on peri- and postoperative somatic parameters were obtained from the electronic patient management system of the hospital six months after the preoperative assessment. RESULTS: LOS of patients with clinically significant depression (N.=296; median: 5 days, interquartile range: 3-8 days) was longer than LOS of patients without depression (N.=2328; median: 4 days, interquartile range: 2-6 days) (P<0.001). A multivariate logistic regression model with the binary dependent variable 'above versus below or equal to the median LOS' revealed that the significant association between depression and LOS persisted (OR: 1.822 [95% CI 1.360-2.441], P<0.001) when simultaneously including the covariates age, gender, ASA classification, Charlson Comorbidity Index, surgical field and POSSUM operative severity rating. CONCLUSION: Data suggest that the association of depression and LOS is independent of the impact of age, gender, surgical field, preoperative physical health, severity of medical comorbidity and extent of surgical procedure. Integration of depression therapy into routine care of surgical patients might be an option to improve outcomes.

Monitoring depth of anaesthesia in a randomized trial decreases the rate of postoperative delirium but not postoperative cognitive dysfunction.

BACKGROUND: Postoperative delirium in elderly patients is a frequent complication and associated with poor outcome. The aim of this parallel group study was to determine whether monitoring depth of anaesthesia influences the incidence of postoperative delirium. METHODS: Patients who were planned for surgery in general anaesthesia expected to last at least 60 min and who were older than 60 yr were included between March 2009 and May 2010. A total of 1277 patients of a consecutive sample were randomized (n=638 open, n=639 blinded) and the data of 1155 patients were analysed (n=575 open, n=580 blinded). In one group, the anaesthesiologists were allowed to use the bispectral index (BIS) data to guide anaesthesia, while in the other group, BIS monitoring was blinded. Cognitive function was evaluated at baseline, 1 week, and 3 months after operation. RESULTS: Delirium incidence was lower in patients guided with BIS. Postoperative delirium was detected in 95 patients (16.7%) in the intervention group compared with 124 patients (21.4%) in the control group (P=0.036). In a multivariate analysis, the percentage of episodes of deep anaesthesia (BIS values <20) were independently predictive for postoperative delirium (P=0.006; odds ratio 1.027). BIS monitoring did not alter the incidence of postoperative cognitive dysfunction (7th day P=0.062; 90th day P=0.372). CONCLUSIONS: Intraoperative neuromonitoring is associated with a lower incidence of delirium, possibly by reducing extreme low BIS values. Therefore, in high-risk surgical patients, this may give the anaesthesiologist a possibility to influence one precipitating factor in the complex genesis of delirium. Clinical trial registration ISRCTN Register: 36437985. http://www.controlled-trials.com/ISRCTN36437985/.

Levetiracetam in patients with central neuropathic post-stroke pain--a randomized, double-blind, placebo-controlled trial.

BACKGROUND AND PURPOSE: Central post-stroke pain (CPSP) is a severe chronic neuropathic pain condition defined as a spontaneous pain or allodynia corresponding to a vascular lesion. It usually evolves weeks after stroke, and can distinctively impair the quality of life. Treatment is complex and mostly unsatisfactory. We hypothesized that the anti-epileptic drug levetiracetam (LEV) improves CPSP compared with placebo. The purpose of this study was to examine the efficacy and tolerability of LEV in patients with CPSP. METHODS: In a double-blind, placebo-controlled, crossover study design patients with CPSP lasting at least 3 months and a pain score ≥ 4 on the 11-point Likert scale were treated over two 8-week periods with a maximum dose up to 3000 mg LEV or placebo. Primary endpoint was a median pain lowering ≥ 2 in the final treatment week compared with the last baseline week. Secondary outcome measures comprised additional pain ratings, depression, sleep quality, quality of life and patients' global impression of change. RESULTS: Of 42 patients, 33 [61.5 years (40-76); 38% women] completed the study. Side effects and withdrawals were more frequent in the LEV (n = 5) group than in the placebo group (n = 1). Patients treated with LEV did not show any improvement of pain or changes in secondary outcome parameters compared with placebo. CONCLUSIONS: LEV is not effective in treatment for CPSP. The mode of action of LEV does not exert an analgesic effect in chronic CPSP.