Discovery of ultrafast spontaneous spin switching in an antiferromagnet by femtosecond noise correlation spectroscopy.

Owing to their high magnon frequencies, antiferromagnets are key materials for future high-speed spintronics. Picosecond switching of antiferromagnetic spin systems has been viewed a milestone for decades and pursued only by using ultrafast external perturbations. Here, we show that picosecond spin switching occurs spontaneously due to thermal fluctuations in the antiferromagnetic orthoferrite Sm0.7Er0.3FeO3. By analysing the correlation between the pulse-to-pulse polarisation fluctuations of two femtosecond optical probes, we extract the autocorrelation of incoherent magnon fluctuations. We observe a strong enhancement of the magnon fluctuation amplitude and the coherence time around the critical temperature of the spin reorientation transition. The spectrum shows two distinct features, one corresponding to the quasi-ferromagnetic mode and another one which has not been previously reported in pump-probe experiments. Comparison to a stochastic spin dynamics simulation reveals this new mode as smoking gun of ultrafast spontaneous spin switching within the double-well anisotropy potential.

Healthcare utilization and unmet needs of patients with antisynthetase syndrome: An international patient survey.

Antisynthease syndrome (ASSD) is a rare, complex and understudied autoimmune disease. Internet-based studies can overcome barriers of traditional on-site research and are therefore very appealing for rare diseases. The aim of this study was to investigate patient-reported symptoms, diagnostic delay, symptoms, medical care, health status, working status, disease knowledge and willingness to participate in research of ASSD patients by conducting an international web-based survey. The multilingual questionnaire was created by an international group of rheumatologists and patients and distributed online. 236 participants from 22 countries completed the survey. 184/236 (78.0%) were female, mean age (SD) was 49.6 years (11.3) and most common antisynthetase antibody was Jo-1 (169/236, 71.6%). 79/236 (33.5%) reported to work full-time. Median diagnostic delay was one year. The most common symptom at disease onset was fatigue 159/236 (67.4%), followed by myalgia 130/236 (55.1%). The complete triad of myositis, arthritis and lung involvement verified by a clinician was present in 42/236 (17.8%) at disease onset and in 88/236 (37.3%) during the disease course. 36/236 (15.3%) reported to have been diagnosed with fibromyalgia and 40/236 (16.3%) with depression. The most reported immunosuppressive treatments were oral corticosteroids 179/236 (75.9%), followed by rituximab 85/236 (36.0%). 73/236 (30.9%) had received physiotherapy treatment. 71/236 (30.1%) reported to know useful online information sources related to ASSD. 223/236 (94.5%) were willing to share health data for research purposes once a year. Our results reiterate that internet-based research is invaluable for cooperating with patients to foster knowledge in rare diseases.

The JAK1/2 inhibitor ruxolitinib in patients with COVID-19 triggered hyperinflammation: the RuxCoFlam trial.

Dysregulated hyperinflammatory response is key in the pathogenesis in patients with severe COVID-19 leading to acute respiratory distress syndrome and multiorgan failure. Whilst immunosuppression has been proven to be effective, potential biological targets and optimal timing of treatment are still conflicting. We sought to evaluate efficacy and safety of the Janus Kinase 1/2 inhibitor ruxolitinib, employing the previously developed COVID-19 Inflammation Score (CIS) in a prospective multicenter open label phase II trial (NCT04338958). Primary objective was reversal of hyperinflammation (CIS reduction of ≥25% at day 7 in ≥20% of patients). In 184 patients with a CIS of ≥10 (median 12) ruxolitinib was commenced at an initial dose of 10 mg twice daily and applied over a median of 14 days (range, 2-31). On day 7, median CIS declined to 6 (range, 1-13); 71% of patients (CI 64-77%) achieved a ≥25% CIS reduction accompanied by a reduction of markers of inflammation. Median cumulative dose was 272.5 mg/d. Treatment was well tolerated without any grade 3-5 adverse events related to ruxolitinib. Forty-four patients (23.9%) died, all without reported association to study drug. In conclusion, ruxolitinib proved to be safe and effective in a cohort of COVID-19 patients with defined hyperinflammation.

High throughput screen of small molecules as potential countermeasures to galactic cosmic radiation induced cellular dysfunction.

Space travel increases galactic cosmic ray exposure to flight crews and this is significantly elevated once travel moves beyond low Earth orbit. This includes combinations of high energy protons and heavy ions such as 56Fe or 16O. There are distinct differences in the biological response to low-energy transfer (x-rays) or high-energy transfer (High-LET). However, given the relatively low fluence rate of exposure during flight operations, it might be possible to manage these deleterious effects using small molecules currently available. Virtually all reports to date examining small molecule management of radiation exposure are based on low-LET challenges. To that end an FDA approved drug library (725 drugs) was used to perform a high throughput screen of cultured cells following exposure to galactic cosmic radiation. The H9c2 myoblasts, ES-D3 pluripotent cells, and Hy926 endothelial cell lines were exposed to a single exposure (75 cGy) using the 5-ion GCRsim protocol developed at the NASA Space Radiation Laboratory (NSRL). Following GCR exposure cells were maintained for up to two weeks. For each drug (@10µM), a hierarchical cumulative score was developed incorporating measures of mitochondrial and cellular function, oxidant stress and cell senescence. The top 160 scores were retested following a similar protocol using 1µM of each drug. Within the 160 drugs, 33 are considered to have an anti-inflammatory capacity, while others also indirectly suppressed pro-inflammatory pathways or had noted antioxidant capacity. Lead candidates came from different drug classes that included angiotensin converting enzyme inhibitors or AT1 antagonists, COX2 inhibitors, as well as drugs mediated by histamine receptors. Surprisingly, different classes of anti-diabetic medications were observed to be useful including sulfonylureas and metformin. Using a hierarchical decision structure, we have identified several lead candidates. That no one drug or even drug class was completely successful across all parameters tested suggests the complexity of managing the consequences of galactic cosmic radiation exposure.

Metachronous hepatic resection for liver only pancreatic metastases.

BACKGROUND: The value of liver resection (LR) for metachronous pancreatic ductal adenocarcinoma (PDAC) metastases remains controversial. However, in light of increasing safety of liver resections, surgery might be a valuable option for metastasized PDAC in selected patients. METHODS: We performed a retrospective, multicenter study including patients undergoing hepatectomy for metachronous PDAC liver metastases between 2004 and 2015 to analyze postoperative outcome and overall survival. All patients were operated with curative intent. Patients with oligometastatic metachronous liver metastasis with definitive chemotherapy (n = 8) served as controls. RESULTS: Overall 25 patients in seven centers were included in this study. The median age at the time of LR was 63.8 years (56.9-69.9) and the median number of metastases in the liver was 1 (IQR 1-2). There were eight non-anatomical resections (32%), 15 anatomical minor (60%) and 2 major LR (8%). Postoperative complications occurred in eleven patients (eight Clavien-Dindo grade I complications (32%) and three grade IIIa complications (12%), respectively). The 30-day mortality was 0%. The median length of stay was 8.6 days (IQR 5-11). Median overall survival following LR was 36.8 months compared to 9.2 months in patients with metachronous liver metastasis with chemotherapy (p = 0007). DISCUSSION: Liver resection for metachronous PDAC metastasis is safe and feasible in selected patients. To address general applicability and to find factors for patient selection, larger trials are urgently warranted.

Microsurgical lymphatic vascular grafting and secondary liposuction: Results of combination treatment in secondary lymphedema.

Surgical treatment of lymphedema with liposuction typically requires subsequent compression therapy. Here we describe an approach where secondary arm lymphedemas are initially treated by autologous lymphatic grafting to bypass the axilla and restore lymphatic flow. In the presence of excess adipose tissue, liposuction is then performed in a second procedure. To assess outcomes, the authors evaluated 28 consecutive adult patients who had undergone secondary liposuction following lymphatic grafting. Arm volumes were measured prior to lymphatic grafting and after the secondary liposuction. The necessity for additional treatment by compression garment and manual lymphatic drainage was assessed prior to lymphatic grafting and after the secondary liposuction following the direct postoperative regimen. The mean arm volumes were reduced significantly (p<0.001) from a mean of 3417± 171 (SEM) cm3 prior to lymphatic grafting to 3020±125 cm3 after reconstruction of the lymphatic vascular system and finally to 2516±104 cm3 after the secondary liposuction (SLS). All 28 adult patients underwent continuous compression and manual lymph-drainage (MLD) prior to the reconstructive surgery. All 28 patients were evaluated regarding necessity of any additional therapy more than 6 months after SLS with a median follow up period of 37 months (range, 7-160 months). 18 of 28 patients did not require any supportive therapy beyond 6 months after SLS to maintain the results. Three patients continued to utilize manual lymphatic drainage, 4 used a combination of MLD and compression therapy and 3 used elastic compression therapy (one patient only while at work). These results indicate that microsurgical restoration of lymphatic outflow followed by SLS eliminates the need for additional treatment in more than two thirds of patients.

Perioperative outcomes and long-term quality of life after total pancreatectomy.

BACKGROUND: Total pancreatectomy is required to treat diseases involving the entire pancreas, and is characterized by high morbidity rates and impaired long-term quality of life (QoL). To date, risk factors associated with perioperative and long-term outcomes have not been determined fully. METHODS: Data from patients undergoing total pancreatectomy between 2000 and 2014 at two high-volume centres were analysed retrospectively to assess risk factors for major surgical complications. Short Form (SF) 36, European Organisation for Research and Treatment of Cancer QLQ-PAN26 and Audit of Diabetes Dependent questionnaires, as well as an original survey were used to investigate factors influencing QoL. RESULTS: A total of 329 consecutive patients underwent total pancreatectomy in the two centres. Overall, total pancreatectomy was associated with a morbidity rate of 59·3 per cent and a 30-day mortality rate of 2·1 per cent. Age over 65 years and long duration of surgery (more than 420 min) were independently associated with major complications (at least Clavien-Dindo grade III). QoL analysis was available for 94 patients (28·6 per cent) with a median follow-up of 63 (i.q.r. 20-109) months; the most common indication for total pancreatectomy in these patients was intraductal papillary mucinous neoplasms (46 per cent). Both physical (PCS) and mental (MCS) component summary scores of SF-36® were lower after total pancreatectomy compared with scores for a normative population (P = 0·020 and P < 0·001 respectively). Linear regression analysis showed that young age, abdominal pain and worse perception of body image were negatively associated with the PCS, whereas diabetes, sexual satisfaction and perception of body image affected MCS. CONCLUSION: Total pancreatectomy can be performed with acceptable morbidity and mortality rates. Older patients had a higher risk of postoperative complications but reported better QoL than younger patients.

ANTECEDENTES: La pancreatectomía total es una cirugía necesaria para tratar enfermedades que afectan a la totalidad el páncreas y se caracteriza por una alta morbilidad y una disminución de la calidad de vida (QoL) a largo plazo. Hasta la fecha, los factores de riesgo asociados a los resultados perioperatorios y a largo plazo no han sido completamente determinados. MÉTODOS: Los datos de los pacientes que se sometieron a una pancreatectomía total desde el año 2000 al 2015 en dos centros de alto volumen se analizaron retrospectivamente para evaluar los factores de riesgo de las complicaciones quirúrgicas mayores. Se utilizaron el SF-36, el EORTC-PAN-26, los cuestionarios ADD-QoL y una encuesta original para investigar los factores que afectan la QoL. RESULTADOS: Un total de 329 pacientes consecutivos se sometieron a una pancreatectomía total en los dos centros. En general, la pancreatectomía total se asoció a un 59,3% de morbilidad y un 2,1% de mortalidad a los 30 días. La edad > 65 años y el tiempo operatorio prolongado (> 420 minutos) se asociaron de forma independiente a las complicaciones Clavien-Dindo ≥ III. El análisis de QoL estuvo disponible en 94 (28,6%) de los pacientes con una mediana de seguimiento de 63 meses (rango intercuartílico 20-109) y la indicación más común fue una neoplasia papilar mucinosa intraductal (IPMN) (45,7%). Las puntuaciones del SF-36 fueron más bajas en ambos componentes sumatorios físico (PCS) y mental (MCS) (P = 0,002; P < 0,001) en comparación con una población normal. El modelo de regresión lineal mostró que la edad joven, el dolor abdominal y la peor percepción de la imagen corporal se asociaron negativamente con el PCS; mientras que la diabetes, la satisfacción sexual y la percepción de la imagen corporal afectaron al MCS. CONCLUSIÓN: Se puede realizar una pancreatectomía total con morbilidad y mortalidad aceptables. Los pacientes de mayor edad tienen un riesgo más elevado de complicaciones postoperatorias, pero presentaron mejor QoL que los pacientes más jóvenes.

Thermal effects of a novel electrosurgical device for focused preparation in breast surgery tested in a specified porcine tissue ex vivo breast model using infrared measurement.

PURPOSE: This article investigates the qualities and thermal effects of a novel electrosurgical device (PT) which has been designed by ERBE Elektromedizin GmbH, Germany, for the preparation of critical locations such as in skin-sparing or nipple-sparing techniques and compares it to a standard device (SD) in a porcine ex vivo breast model using an heat map generated by infrared thermography. METHODS: In total, 42 abdominal wall specimens of porcine tissue consisting of the skin and the underlying subcutaneous and muscle layer were alternately dissected using one of the devices and pre-settings. During the preparation with the two devices, the epicutaneous temperature was measured by an infrared camera (VarioCam, Jenoptik, Germany) and the maximum temperature as well as the slope of the temperature rise was analysed. RESULTS: The use of PT shows significantly lower values for [Formula: see text] compared to SD. This effect was independent from the chosen mode. Using the same instrument in different modes, the use of AutoCut mode showed a significant reduction of [Formula: see text] at all indicated time points (SD: p < 0.0001 and PT: p < 0.0001). In summary, the combination of AutoCut + PT showed the lowest rise in temperature, whereas the combination of DryCut + SD led to the highest rise in temperature. The temperature difference between these two settings was 13.84 °C, which means a possible temperature reduction of 67% can be achieved by the right choice of device and its tailored mode. CONCLUSIONS: The novel PT shows a significant reduction in epicutaneous temperature and a significant reduction of the slope of temperature rise most probably by a more focused application of energy compared to SD.

Liberal fluid fasting: impact on gastric pH and residual volume in healthy children undergoing general anaesthesia for elective surgery.

BACKGROUND: The paediatric preoperative fasting time of 2 h for clear fluids, as suggested by guidelines, is often exceeded. Shorter preoperative fasting has been proposed to avoid potential outcomes such as dehydration, ketoacidosis, reduced arterial blood pressure, and patient discomfort. The aim of this study was to investigate whether liberal clear fluid intake until premedication significantly reduces actual fasting time and impacts gastric pH and residual volume. METHODS: Children (1-16 yr old, ASA I or II) undergoing elective procedures with general anaesthesia requiring tracheal intubation were randomised for clear fluid intake until premedication with midazolam (liberal) or 2 h fluid fasting (standard). Actual fasting times were recorded. Gastric content was sampled after tracheal intubation with an orogastric tube to determine gastric pH and residual volume. Data are presented as median [interquartile range]. RESULTS: We included 162 children aged 1.1-16 yr; gastric pH was determined in 138 patients. Patients' characteristics were similar in the two groups. The liberal fasting group had significantly shorter fasting times (48 [18.5-77.5] vs 234 [223.5-458.5] min; P<0.001). No significant difference was observed regarding gastric pH (1.6 [1.5-1.8] vs 1.6 [1.4-1.7]; P=0.237) or residual volume (0.38 [0.1-1.1] vs 0.43 [0.13-0.73] ml kg-1; P=0.535). Twelve patients (15%) in the liberal group (median fluid fasting 32 min) vs one patient (1%) had gastric residual volumes >2 ml kg-1 (P=0.001). CONCLUSION: Fluid intake until premedication allows for significantly shorter fasting times. Elevated gastric residual volumes may occur more often in patients with fasting times of 30 min or shorter. CLINICAL TRIAL REGISTRATION: NCT02603094.

Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial.

Background: Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor shown to improve survival in advanced solid cancers. We evaluated the role of adjuvant bevacizumab in melanoma patients at high risk of recurrence. Patients and methods: Patients with resected AJCC stage IIB, IIC and III cutaneous melanoma were randomised to receive either adjuvant bevacizumab (7.5 mg/kg i.v. 3 weekly for 1 year) or standard observation. The primary end point was detection of an 8% difference in 5-year overall survival (OS) rate; secondary end points included disease-free interval (DFI) and distant metastasis-free interval (DMFI). Tumour and blood were analysed for prognostic and predictive markers. Results: Patients (n=1343) recruited between 2007 and 2012 were predominantly stage III (73%), with median age 56 years (range 18-88 years). With 6.4-year median follow-up, 515 (38%) patients had died [254 (38%) bevacizumab; 261 (39%) observation]; 707 (53%) patients had disease recurrence [336 (50%) bevacizumab, 371 (55%) observation]. OS at 5 years was 64% for both groups [hazard ratio (HR) 0.98; 95% confidence interval (CI) 0.82-1.16, P = 0.78). At 5 years, 51% were disease free on bevacizumab versus 45% on observation (HR 0.85; 95% CI 0.74-0.99, P = 0.03), 58% were distant metastasis free on bevacizumab versus 54% on observation (HR 0.91; 95% CI 0.78-1.07, P = 0.25). Forty four percent of 682 melanomas assessed had a BRAFV600 mutation. In the observation arm, BRAF mutant patients had a trend towards poorer OS compared with BRAF wild-type patients (P = 0.06). BRAF mutation positivity trended towards better OS with bevacizumab (P = 0.21). Conclusions: Adjuvant bevacizumab after resection of high-risk melanoma improves DFI, but not OS. BRAF mutation status may predict for poorer OS untreated and potential benefit from bevacizumab. Clinical Trial Information: ISRCTN 81261306; EudraCT Number: 2006-005505-64.

Tube tip and cuff position using different strategies for placement of currently available paediatric tracheal tubes.

BACKGROUND: Tracheal tube tip and cuff positions of different cuffed paediatric tracheal tube brands in the trachea can vary with design. METHODS: Data from three clinical studies with measured tracheal lengths were pooled in a database including 422 children aged from birth to 16 yr. Dimensional data of seven cuffed paediatric tracheal tube brands (ID 3.0-7.0 mm) were recorded. Positions of tracheal tube tip and upper cuff border were calculated for each of the 422 tracheas using depth mark based tracheal tube placement, placement of the tracheal tube tip at a calculated safety distance above the carina, and mid-tracheal tube placement. Percentage of accidental bronchial intubations and tracheal tube cuff positions in the subglottic or supraglottic region were calculated. RESULTS: Depth mark based tracheal tube placement resulted in accidental bronchial intubation of up to 18% of cases and tracheal tube cuffs being placed in the subglottic region in up to 91%. Tracheal tube tip placement at a calculated safety distance resulted in up to 54% of tube cuffs placed too high. Mid-tracheal tube placement led to 100% subglottic or supraglottic tracheal tube cuff positions. CONCLUSIONS: All studied cuffed paediatric tracheal tubes have major design flaws potentially leading to airway complications. Tracheal tube manufacturers are urgently asked to improve the design of cuffed paediatric tracheal tubes. Alternative strategies for tracheal tube placement can allow safe tracheal tube placement of uncuffed but not of cuffed tracheal tubes.

Genetic And Morphological Evaluation (GAME) score for patients with colorectal liver metastases.

BACKGROUND: This study sought to develop a clinical risk score for resectable colorectal liver metastasis (CRLM) by combining clinicopathological and clinically available biological indicators, including KRAS. METHODS: A cohort of patients who underwent resection for CRLM at the Johns Hopkins Hospital (JHH) was analysed to identify independent predictors of overall survival (OS) that can be assessed before operation; these factors were combined into the Genetic And Morphological Evaluation (GAME) score. The score was compared with the current standard (Fong score) and validated in an external cohort of patients from the Memorial Sloan Kettering Cancer Center (MSKCC). RESULTS: Six preoperative predictors of worse OS were identified on multivariable Cox regression analysis in the JHH cohort (502 patients). The GAME score was calculated by allocating points to each patient according to the presence of these predictive factors: KRAS-mutated tumours (1 point); carcinoembryonic antigen level 20 ng/ml or more (1 point), primary tumour lymph node metastasis (1 point); Tumour Burden Score between 3 and 8 (1 point) or 9 and over (2 points); and extrahepatic disease (2 points). The high-risk group in the JHH cohort (GAME score at least 4 points) had a 5-year OS rate of 11 per cent, compared with 73·4 per cent for those in the low-risk group (score 0-1 point). Importantly, in cohorts from both the JHH and MSKCC (747 patients), the discriminatory capacity of the GAME score was superior to that of the Fong score, as demonstrated by the C-index and the Akaike information criterion. CONCLUSION: The GAME score is a preoperative prognostic tool that can be used to inform treatment selection.

Trends in use of lymphadenectomy in surgery with curative intent for intrahepatic cholangiocarcinoma.

BACKGROUND: The role of routine lymph node dissection (LND) in the surgical treatment of intrahepatic cholangiocarcinoma (ICC) remains controversial. The objective of this study was to investigate the trends of LND use in the surgical treatment of ICC. METHODS: Patients undergoing curative intent resection for ICC in 2000-2015 were identified from an international multi-institutional database. Use of lymphadenectomy was evaluated over time and by geographical region (West versus East); LND use and final nodal status were analysed relative to AJCC T categories. RESULTS: Among the 1084 patients identified, half (535, 49·4 per cent) underwent concomitant hepatic resection and LND. Between 2000 and 2015, the proportion of patients undergoing LND for ICC nearly doubled: 44·4 per cent in 2000 versus 81·5 per cent in 2015 (P < 0·001). Use of LND increased over time among both Eastern and Western centres. The odds of LND was associated with the time period of surgery and the extent of the tumour/T status (referent T1a: OR 2·43 for T2, P = 0·001; OR 2·13 for T3, P = 0·016). Among the 535 patients who had LND, lymph node metastasis (LNM) was noted in 209 (39·1 per cent). Specifically, the incidence of LNM was 24 per cent in T1a disease, 22 per cent in T1b, 42·9 per cent in T2, 48 per cent in T3 and 66 per cent in T4 (P < 0·001). AJCC T3 and T4 categories, harvesting of six or more lymph nodes, and presence of satellite lesions were independently associated with LNM. CONCLUSION: The rate of LNM was high across all T categories, with one in five patients with T1 disease having nodal metastasis. The trend in increased use of LND suggests a growing adoption of AJCC recommendations in the treatment of ICC.

Early versus late recurrence of intrahepatic cholangiocarcinoma after resection with curative intent.

BACKGROUND: The objective of this study was to investigate the characteristics, treatment and prognosis of early versus late recurrence of intrahepatic cholangiocarcinoma (ICC) after hepatic resection. METHODS: Patients who underwent resection with curative intent for ICC were identified from a multi-institutional database. Data on clinicopathological characteristics, initial operative details, timing and sites of recurrence, recurrence management and long-term outcomes were analysed. RESULTS: A total of 933 patients were included. With a median follow-up of 22 months, 685 patients (73·4 per cent) experienced recurrence of ICC; 406 of these (59·3 per cent) developed only intrahepatic disease recurrence. The optimal cutoff value to differentiate early (540 patients, 78·8 per cent) versus late (145, 21·2 per cent) recurrence was defined as 24 months. Patients with early recurrence had extrahepatic disease more often (44·1 per cent versus 28·3 per cent in those with late recurrence; P < 0·001), whereas late recurrence was more often only intrahepatic (71·7 per cent versus 55·9 per cent for early recurrence; P < 0·001). From time of recurrence, overall survival was worse among patients who had early versus late recurrence (median 10 versus 18 months respectively; P = 0·029). In multivariable analysis, tumour characteristics including tumour size, number of lesions and satellite lesions were associated with an increased risk of early intrahepatic recurrence. In contrast, only the presence of liver cirrhosis was independently associated with an increased likelihood of late intrahepatic recurrence (hazard ratio 1·99, 95 per cent c.i. 1·11 to 3·56; P = 0·019). CONCLUSION: Early and late recurrence after curative resection for ICC are associated with different risk factors and prognosis. Data on the timing of recurrence may inform decisions about the degree of postoperative surveillance, as well as help counsel patients with regard to their risk of recurrence.

Effectiveness of tip rotation in fibreoptic bronchoscopy under different experimental conditions: an in vitro crossover study.

Background: Proper manipulation of fibreoptic bronchoscopes is essential for successful tracheal intubation or diagnostic bronchoscopy. Failure of proper navigation and rotation of the fibrescope may lead to difficulties in advancing the fibrescope and might also be responsible for (unnecessary) difficulties and delays in fibreoptic tracheal intubation, with subsequent hypoxaemia. The present study, therefore, aimed to assess the effectiveness of tip rotation in flexible bronchoscopes in different experimental conditions. Methods: Five differently sized pairs of fibrescopes (outer diameters of 2.2, 2.4, 3.5, 4.2, and 5.2 mm) were inserted into paediatric airway manikins via an appropriately sized laryngeal mask and were turned clockwise or anticlockwise at the fibrescope body or cord to 45, 90, and 180°, with the cord held either straight or bent. The primary outcome measure was the ratio of rotation measured at the tip over the rotation performed with the fibrescope body or cord. Results: Overall, the 'body' turn was significantly less effective when a bent cord was present (mean difference ranging from 29.8% (95% confidence interval 8.8-50.9) to 117.4% (93.6-141.2). This difference was diminished when the 'cord' turn was performed. Smaller fibrescopes, with outer diameters of 2.2 and 2.4 mm, were inferior with respect to the transmission of 'body' rotation to the tip. Conclusions: 'Cord' turning of the fibrescope appears to be more effective in rotating the tip than a turn of the fibrescope 'body' only. Straightening the fibrescope cord and combined 'body' and 'cord' turning are recommended.

Complement C5a-Induced Changes in Neutrophil Morphology During Inflammation.

The complement and neutrophil defence systems, as major components of innate immunity, are activated during inflammation and infection. For neutrophil migration to the inflamed region, we hypothesized that the complement activation product C5a induces significant changes in cellular morphology before chemotaxis. Exposure of human neutrophils to C5a dose- and time-dependently resulted in a rapid C5a receptor-1 (C5aR1)-dependent shape change, indicated by enhanced flow cytometric forward-scatter area values. Similar changes were observed after incubation with zymosan-activated serum and in blood neutrophils during murine sepsis, but not in mice lacking the C5aR1. In human neutrophils, Amnis high-resolution digital imaging revealed a C5a-induced decrease in circularity and increase in the cellular length/width ratio. Biomechanically, microfluidic optical stretching experiments indicated significantly increased neutrophil deformability early after C5a stimulation. The C5a-induced shape changes were inhibited by pharmacological blockade of either the Cl-/HCO3--exchanger or the Cl- -channel. Furthermore, actin polymerization assays revealed that C5a exposure resulted in a significant polarization of the neutrophils. The functional polarization process triggered by ATP-P2X/Y-purinoceptor interaction was also involved in the C5a-induced shape changes, because pretreatment with suramin blocked not only the shape changes but also the subsequent C5a-dependent chemotactic activity. In conclusion, the data suggest that the anaphylatoxin C5a regulates basic neutrophil cell processes by increasing the membrane elasticity and cell size as a consequence of actin-cytoskeleton polymerization and reorganization, transforming the neutrophil into a migratory cell able to invade the inflammatory site and subsequently clear pathogens and molecular debris.

Intraoperative music application in children and adolescents - a pilot study.

BACKGROUND: Hospitalization, surgery and anaesthesia may lead to new-onset maladaptive behaviour, emotional distress and trauma. This pilot study aims to investigate the influence of intraoperatively applied music on post-operative behaviour in children and adolescents. METHODS: Children with an ASA physical state classification of I or II, aged from 4 to 16 years and scheduled for elective circumcision or inguinal hernia repair under combined general and caudal anaesthesia were included. The children were randomized into two groups. They wore headphones during surgery, and were either exposed to music or not. All involved staff were blinded. Post-operative behaviour was documented by parents on day 7, 14 and 28 after surgery, using a questionnaire adapted from the "Post Hospitalization Behavioural Questionnaire" (PHBQ). Overall occurrence of at least one item indicating maladaptive behaviour was the primary outcome. Data are presented as median (interquartile range). RESULTS: In total, 135 children aged 6.6 (5.3-8.5) years, weighing 22 (19-29) kg, were included, with 112 completed questionnaires returned. Overall occurrence of at least one maladaptive item was lower in the music group, with a significantly lower incidence on day 7 (51% vs. 77% in controls; P < 0.01). CONCLUSION: Intraoperative music application in children undergoing minor surgical procedures may reduce the incidence of post-operative maladaptive behaviour within the first week.