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Background Acute exacerbations of fibrosing interstitial lung diseases (ILDs) are associated with high mortality. We used prospective data from the INBUILD trial to investigate risk factors for acute exacerbations and the impact of these events in patients with progressive pulmonary fibrosis. Methods Patients with progressive fibrosing ILDs other than idiopathic pulmonary fibrosis (IPF) were randomised to receive nintedanib or placebo. Associations between baseline characteristics and time to first acute exacerbation were assessed using pooled data from both treatment groups using Cox proportional hazard models, firstly univariable models and then a multivariable model using forward stepwise selection. The risk of death was estimated based on the Kaplan−Meier method. Results Over a median follow-up of approximately 19 months, acute exacerbations were reported in 58 (8.7%) of 663 patients. In the risk factor analysis, the final model included diffusing capacity of the lung for carbon monoxide (DLCO) % predicted, treatment and age. Lower DLCO % predicted was associated with an increased risk of acute exacerbation with a hazard ratio (HR) of 1.56 (95% CI 1.21–2.02) per 10 units lower (p

Cryptogenic organizing pneumonia is a rare idiopathic interstitial lung disease, with a well-defined clinical-radiological and pathological entity. It may also be secondary to several causes. Rapid clinical and imaging improvement is usually obtained with corticosteroid therapy. We report here, to the best of our knowledge, a unique case of organizing pneumonia associated with Sertraline, a selective serotonin reuptake inhibitor, commonly used in antidepressant therapy.

Objectives. This study aimed to investigate the consistency between results of the American Conference for Governmental Occupational Hygienists (ACGIH) threshold limit value (TLV) for hand activity and proposed action levels of objective measurements in risk assessments of work-related musculoskeletal disorders. Methods. Wrist velocities and forearm muscular load were measured for 11 assemblers during one working day. Simultaneously, each assembler's hand activity level (HAL) during three sub-cycles was rated twice on two separate occasions by two experts, using a HAL scale. Arm/hand exertion was also rated by the assemblers themselves using a Borg scale. In total, 66 sub-cycles were assessed and assigned to three exposure categories: A) below ACGIH action limit (AL) (green); B) between AL and TLV (yellow); and C) above TLV (red). The median wrist velocity and the 90 th percentile of forearm muscular load obtained from the objective measurements corresponding to the sub-cycles were calculated and assigned to two exposure categories: A) below or C) above the proposed action level. Results. The agreement between ACGIH TLV for hand activity and the proposed action level for wrist velocity was 87%. Conclusions. The proposed action level for wrist velocity is highly consistent with the TLV. Additional studies are needed to confirm the results.

Background and Objective: Real-life data on suspected familial fibrosis, defined as the occurrence of the disease in a patient younger than 50 and/or having at least one relative affected by pulmonary fibrosis remain scarce., Methods: The Belgian and Luxembourg IPF registry (PROOF-Next) is a multicentric prospective longitudinal and observational study set in Belgium and Luxembourg. We compared characteristics and clinical course of patients with suspected familial pulmonary fibrosis (FPF) and sporadic IPF., Results: We included 618 patients in the analysis, of whom 76 (12%) fulfilled criteria for FPF. They were significantly younger than sIPF (median age (range) 65 (43-87), vs. 72 (51-98), p = 0.0001). Male gender proportion and smoking status did not differ between groups, but the number of pack-year among current and former smokers was lower in FPF (20 vs. 25, p = 0.02). Besides, 87% of FPF and 76% of sIPF were treated with antifibrotic (p = 0.047). Baseline pulmonary function tests were similar in both groups, as well as median time before progression and transplant-free survival. Finally, genetic testing, performed in a minority, led to the identification of 10 telomerase-related gene variants., Conclusion: Although younger and exposed to less tobacco, patients with FPF show an equally aggressive progression as observed in sporadic IPF patients. These results warrant early referral of FPF patients to expert centres for optimal management., (© 2023 Asian Pacific Society of Respirology.)

Background: Interstitial lung disease (ILD) is associated with a higher lung cancer (LC) risk and may impact cancer's clinical characteristics, treatment strategies, and outcomes. This impact's extent is unclear, particularly in Caucasians., Methods: In this retrospective observational study, we reviewed the files of all LC patients diagnosed in a 38-month period. Expert radiologists reviewed the computed tomography scans performed at diagnosis. Patients with LC and ILD ( n = 29, 7%) were compared to those without ILD ( n = 363, 93%) for population and cancer characteristics, treatments, and clinical outcomes., Results: Patients with LC and ILD were older (73 ± 8 vs. 65 ± 11 years; p < 0.001). There was no significant difference in LC histology, localization, stage, or treatment modalities. The respiratory complication rate after cancer treatment was significantly higher in the ILD group (39% vs. 6%; p < 0.01). Overall survival rates were similar at 12 (52% vs. 59%; p = 0.48) and 24 months (41% vs. 45%; p = 0.64) but poorer in the ILD group at 36 months, although not statistically significant (9% vs. 39%; p = 0.06). The ILD group had a higher probability of death (hazard ratio (HR) = 1.49 [0.96;2.27]), but this was not statistically significant ( p = 0.06). In a Cox regression model, patients with ILD treated surgically had a significantly higher mortality risk (HR = 2.37 [1.1;5.09]; p = 0.03)., Conclusions: Patients with combined LC and ILD have worse clinical outcomes even when similar treatment modalities are offered.

Background: Cleaning workers are exposed to chemicals and high physical workload, commonly resulting in airway problems and pain. In this study the response in the upper airways and the physical workload following airborne and ergonomic exposure of cleaning spray was investigated., Methods: A survey was answered by professional cleaning workers to investigate their use of cleaning sprays and the perceived effects on eyes, airways and musculoskeletal pain. A human chamber exposure study was then conducted with 11 professional cleaning workers and 8 non-professional cleaning workers to investigate the airborne exposure, acute effects on eyes and airways, and physical load during cleaning with sprays, foam application and microfiber cloths premoistened with water. All cleaning products used were bleach, chlorine, and ammonia free. The medical assessment included eye and airway parameters, inflammatory markers in blood and nasal lavage, as well as technical recordings of the physical workload., Results: A high frequency of spray use (77%) was found among the 225 professional cleaning workers that answered the survey. Based on the survey, there was an eight times higher risk (p < 0.001) of self-experienced symptoms (including symptoms in the nose, eyes and throat, coughing or difficulty breathing) when they used sprays compared to when they cleaned with other methods. During the chamber study, when switching from spray to foam, the airborne particle and volatile organic compound (VOC) concentrations showed a decrease by 7 and 2.5 times, respectively. For the whole group, the peak nasal inspiratory flow decreased (-10.9 L/min, p = 0.01) during spray use compared to using only water-premoistened microfiber cloths. These effects were lower during foam use (-4.7 L/min, p = 0.19). The technical recordings showed a high physical workload regardless of cleaning with spray or with water., Conclusion: Switching from a spraying to a foaming nozzle decreases the exposure of both airborne particles and VOCs, and thereby reduces eye and airway effects, and does not increase the ergonomic load. If the use of cleaning products tested in this study, i.e. bleach, chlorine, and ammonia free, cannot be avoided, foam application is preferable to spray application to improve the occupational environment., (© 2023. The Author(s).)

Introduction: The PROOF registry is a prospective, observational study that aimed to monitor disease progression in a real-world cohort of patients with idiopathic pulmonary fibrosis (IPF). Here, longitudinal quality-of-life (QoL) outcomes, healthcare resource use (HCRU), and the association between QoL and mortality in patients enrolled in the PROOF registry are presented., Methods: QoL outcomes (St. George's Respiratory Questionnaire [SGRQ], EuroQoL-5 dimensions-5 levels Health Questionnaire [EQ-5D-5L], EuroQoL-5 dimensions Health Questionnaire [EQ-5D] visual analogue scale [VAS] and cough VAS) and HCRU were collected for all patients. Associations between baseline QoL and mortality were assessed using univariate and multivariate analyses. During multivariate analyses, individual QoL measures were adjusted for the following covariates: age, sex, percent predicted forced vital capacity, percent predicted diffusing capacity of the lungs for carbon monoxide, smoking status, and supplementary oxygen use at registry inclusion., Results: In total, 277 patients were enrolled in the PROOF registry. During the follow-up period, worsening in cough VAS score, SGRQ symptom score, and SGRQ activity score was observed, while EQ-5D VAS, SGRQ total score, and SGRQ impact score remained stable. During univariate analyses, EQ-5D VAS and all SGRQ sub-scores and total score at baseline were associated with mortality; however, during multivariate analyses, only the SGRQ total score, SGRQ impact score, and SGRQ symptom score at baseline were associated with mortality. During the follow-up period, 261 (94.2%) patients required an outpatient consultation (IPF- or non-IPF-related) and there were 182 hospitalizations in total, most of which were respiratory related (66.5%)., Conclusions: The PROOF registry provided valuable, real-world data on the association between baseline QoL and mortality, and longitudinal HCRU and QoL outcomes in patients with IPF over 24 months and identified that SGRQ may be an independent prognostic factor in IPF., (© 2022. The Author(s).)

Serial crystallography of membrane proteins often employs high-viscosity injectors (HVIs) to deliver micrometre-sized crystals to the X-ray beam. Typically, the carrier medium is a lipidic cubic phase (LCP) media, which can also be used to nucleate and grow the crystals. However, despite the fact that the LCP is widely used with HVIs, the potential impact of the injection process on the LCP structure has not been reported and hence is not yet well understood. The self-assembled structure of the LCP can be affected by pressure, dehydration and temperature changes, all of which occur during continuous flow injection. These changes to the LCP structure may in turn impact the results of X-ray diffraction measurements from membrane protein crystals. To investigate the influence of HVIs on the structure of the LCP we conducted a study of the phase changes in monoolein/water and monoolein/buffer mixtures during continuous flow injection, at both atmospheric pressure and under vacuum. The reservoir pressure in the HVI was tracked to determine if there is any correlation with the phase behaviour of the LCP. The results indicated that, even though the reservoir pressure underwent (at times) significant variation, this did not appear to correlate with observed phase changes in the sample stream or correspond to shifts in the LCP lattice parameter. During vacuum injection, there was a three-way coexistence of the gyroid cubic phase, diamond cubic phase and lamellar phase. During injection at atmospheric pressure, the coexistence of a cubic phase and lamellar phase in the monoolein/water mixtures was also observed. The degree to which the lamellar phase is formed was found to be strongly dependent on the co-flowing gas conditions used to stabilize the LCP stream. A combination of laboratory-based optical polarization microscopy and simulation studies was used to investigate these observations., (open access.)

There are several well-known risk factors for work-related musculoskeletal disorders (MSDs). Despite this knowledge, too many people still work in harmful conditions. The absence of occupational exposure limits (OELs) for physical workload impedes both supervision and preventive work. To prevent myalgia, tendon disorders, and nerve entrapments in the upper musculoskeletal system, we propose action levels concerning work postures, movement velocities and muscular loads recorded by wearable equipment. As an example, we propose that wrist velocity should not exceed 20°/s as a median over a working day. This has the potential to reduce the prevalence of carpal tunnel syndrome (CTS) in highly exposed male occupational groups by 93%. By reducing upper arm velocity in highly exposed female groups to the suggested action level 60°/s, the prevalence of pronounced neck/shoulder myalgia with clinical findings (tension neck syndrome) could be reduced by 22%. Furthermore, we propose several other action levels for the physical workload. Our ambition is to start a discussion concerning limits for physical workload, with the long-term goal that OELs shall be introduced in legislation. Obviously, the specific values of the proposed action levels can, and should, be discussed. We hope that quantitative measurements, combined with action levels, will become an integral part of systematic occupational health efforts, enabling reduction and prevention of work-related MSDs., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Purpose. This study aimed to investigate the effects of using hand grip or resisted wrist extension as the reference contraction, and two electrode positions, on field recordings of forearm extensor muscle activity. Materials and methods . Right forearm extensor muscle activity was recorded using two electrode pairs (over the most prominent part (position 2) and proximal to that (position 1)) during one working day in 13 female hotel housekeepers. Each subject performed the two maximal voluntary contractions (MVCs), and the electrical activity obtained during these (maximal voluntary electrical activity (MVE)) was used for normalization. Each set of recordings was analysed twice, once using hand grip as the MVC and once using resisted wrist extension. Results . Resisted wrist extension showed a higher group mean MVE than hand grip. Position 2 had higher correlation between MVE and force during the MVCs. The workload during cleaning was lower when using resisted wrist extension as reference than when using hand grip (24%MVE vs 46%MVE; p  = 0.002 at position 2) for the 90th percentile. The workload (99th percentile) was overestimated in two subjects when using hand grip as reference. Conclusions. Problems associated with poorly activated forearm extensors can be overcome by using resisted wrist extension as reference.

Background: Nintedanib (Ofev ® ) and pirfenidone (Esbriet ® ) are recommended by international guidelines as treatment options for idiopathic pulmonary fibrosis (IPF)., Objectives: To compare the cost-effectiveness of nintedanib with that of pirfenidone for the treatment of IPF from a Belgian healthcare payer perspective., Methods: The economic analysis used a Markov model that calculated outcomes over patient lifetime. Overall survival was assumed to be the same for the two comparators. Data from a network meta-analysis were used for loss of lung function, acute exacerbation events, safety and treatment discontinuation (for any reason). The health-state utility estimates in the model were calculated from EQ-5D scores collected in nintedanib studies. The assumed resource use for background care was also based on patient-level data that were categorised to fit the health states in the model and synthesised with costs and tariffs from Belgian national databases., Results: Treatment with nintedanib resulted in an estimated total cost of €102,315, which was less than the total cost of treatment with pirfenidone (€113,313). Given the similarities in the survival and progression outcomes obtained with nintedanib and pirfenidone, the model predicted near equivalence in total QALYs (3.353 QALYs for the nintedanib arm and 3.318 for the pirfenidone arm). Results were largely driven by model assumptions underlying mortality, acute exacerbations and treatment discontinuation., Conclusions: After performing a synthesis of the most recently published evidence for IPF patients and assuming a Belgian healthcare payer perspective, we found nintedanib to be more cost-saving than pirfenidone.

Introduction: Idiopathic chronic eosinophilic pneumonia (ICEP) is an orphan lung disease characterized by concomitant systemic and local eosinophilia, along with bilateral lung infiltrates. Symptoms include dyspnea of subacute/chronic onset, cough, and general systemic signs. Although all patients do respond to oral corticosteroids, relapse rate is very high, which highlights the need for alternative therapies in case of relapsing ICEP. Mepolizumab is a fully humanized antibody directed against interleukin 5, a key growth factor of eosinophils. In the present study, we retrospectively studied the effect of off-label use of mepolizumab for relapsing ICEP., Materials and Methods: All data from patients treated with mepolizumab for relapsing ICEP were included in our database and diagnoses were reviewed. We analyzed the effect of treatment on relapse rate, oral corticosteroids (OCS) use, and lung lesions on high-resolution computed tomography (HRCT)., Results: We included ten patients in the final analysis, with a median follow-up of 9 months after initiation of mepolizumab. Beside its expected effect on circulating eosinophils, treatment with mepolizumab was associated with a significant reduction of annual rate of exacerbations and a reduced consumption of corticosteroids. We also observed a remission of lung lesions on follow-up HRCT., Conclusions: In this open-label retrospective study, treatment of ICEP with mepolizumab was associated with a reduction of relapses, OCS use, and the disappearance of lung infiltrates.

Background: The PROOF registry is an observational study initiated in October 2013 with the aim to monitor disease progression in a real-world population of patients with idiopathic pulmonary fibrosis (IPF). Here, we present longitudinal clinical outcomes from the PROOF registry., Methods: Patients with IPF were enrolled across eight centers in Belgium and Luxembourg. For all patients, clinical outcomes data were collected, including mortality, lung transplant, acute exacerbations, and pulmonary hypertension. For patients treated with pirfenidone at any time during follow-up (2013-2017), for any duration of treatment (the pirfenidone-treated population): pirfenidone treatment patterns were collected; changes in pulmonary function (forced vital capacity [FVC] and carbon monoxide diffusing capacity [DLco]) were reviewed up to 24 months post-inclusion; and time-to-event analyses from the time of registry inclusion were performed., Results: The PROOF registry enrolled a total of 277 patients. During follow-up, 23.1% of patients died, 5.1% received a lung transplant, 5.4% experienced an acute exacerbation, and 6.1% had comorbid pulmonary hypertension. In the pirfenidone-treated population (N = 233, 84.1%), 12.9% of patients had a temporary dose discontinuation and 31.8% had a temporary dose reduction; 4.3% of patients permanently discontinued pirfenidone due to an adverse drug reaction. Mean percent predicted FVC was 81.2% (standard deviation [SD] 19.0) at Month 0 and 78.3% (SD 25.0) at Month 24, and mean percent predicted DLco was 47.0% (SD 13.2) and 45.0% (SD 16.5), respectively. Rates of ≥ 10% absolute decline in percent predicted FVC and ≥ 15% absolute decline in percent predicted DLco over 24 months were 31.0% and 23.2%, respectively. Mean times from registry inclusion to categorical absolute decline in percent predicted FVC and percent predicted DLco were 20.1 (standard error [SE] 0.6) months and 23.4 (SE 0.5) months, respectively; mean time from registry inclusion to death was 31.0 (SE 0.9) months., Conclusions: The PROOF registry is a source of European data characterizing longitudinal clinical outcomes of patients with IPF. Over 12 months of follow-up, pulmonary function remained largely stable in patients with IPF who received pirfenidone for any duration of treatment. Pulmonary function remained similar at 24 months of follow-up, although patient numbers were lower., Trial Registration: PROOF is registered with the relevant authorities in Belgium and Luxembourg, with registration to Comité National d'Éthique et de Recherche (CNER) N201309/03-12 September 2013 and a notification to Comité National de Protection des Données (CNDP) for Luxembourg.

Introduction: PROOF (a Prospective Observational Registry to Describe the Disease Course and Outcomes of Idiopathic Pulmonary Fibrosis) is an ongoing, observational registry initiated in 2013 with the aim of collecting real-world data from patients with idiopathic pulmonary fibrosis (IPF). Here, we present comprehensive baseline data, which were collected from patients on registry inclusion., Methods: Patients with IPF were enrolled across eight centres in Belgium and Luxembourg. Baseline data collected included demographics, diagnostic information and clinical characteristics, including lung function and health-related quality of life. Data on comorbidities and prescribed medication were also collected., Results: A total of 277 patients were enrolled in the PROOF registry. At inclusion, 92.8% and 6.5% of patients had a definite or probable diagnosis of IPF, respectively. Mean per cent predicted forced vital capacity and carbon monoxide diffusing capacity were 80.6% and 46.9%, respectively. Mean St. George's Respiratory Questionnaire total score was 47.0, and mean Cough-Visual Analogue Scale score was 30.5 mm. The most prevalent comorbidities reported at inclusion were gastrointestinal disorders (50.2%), including gastro-oesophageal reflux disease (47.3%) and metabolism and nutrition disorders (39.7%). At inclusion, 67.2% and 2.2% of patients were prescribed pirfenidone and nintedanib, respectively, with treatment initiated either prior to, or at the time of, inclusion. Medication prescribed concomitantly with pirfenidone included antihypertensives (54.8%), statins (37.1%) and prophylactic antithrombotics/anticoagulants (36.6%)., Conclusion: The PROOF registry provides valuable demographic and clinical data from a real-world population of patients with IPF in Belgium and Luxembourg, demonstrating the high burden of comorbidities and prescribed medication in these patients. Longitudinal data from this patient population will be investigated in future analyses., Trial Registration: PROOF is registered with the relevant authorities in Belgium and Luxembourg, with registration to Comité National d'Éthique et de Recherché (CNER) N201309/03 - 12 September 2013 and a notification to Comité National de Protection des Données (CNDP)., Competing Interests: Competing interests: WAW, BB, CD and HS have received consulting and/or lecture fees from F. Hoffman-La Roche, Ltd. and Boehringer Ingelheim. KUK and KB are employees of Roche-Genentech and hold shares.

Background: To reduce ergonomic risk factors in terms of awkward and constrained postures and high velocities, it is important to perform adequate risk assessments. Technical methods provide objective measures of physical workload. These methods have so far mainly been used by researchers. However, if written instructions how to apply the sensors and how to adopt the reference posture are provided, together with triaxial accelerometers, it may be possible for employees to record their own physical workload. The exposure in terms of e.g. upper arm elevations could then easily be assessed for all workers in a workplace. The main aims of this study were: 1) to compare analyses for self-recording of upper arm elevation during work using a simplified reference posture versus using a standard reference posture, and 2) to compare the two reference postures., Methods: Twenty-eight cleaners attached an accelerometer to their dominant upper arm and adopted a simplified reference according to a written instruction. They were thereafter instructed by a researcher to adopt a standard reference. Upper arm elevations were recorded for 2 or 3 days. Each recording was analysed twice; relative to the simplified reference posture and relative to the standard reference posture. The group means of the differences in recorded upper arm elevations between simplified and standard reference analyses were assessed using Wilcoxon signed ranks test. Furthermore, we calculated the group mean of the differences between the simplified reference posture and the standard reference posture., Results: For arm elevation during work (50 th percentile), the group mean of the differences between the two analyses was 0.2° (range -7 - 10°). The group mean of the differences between the two references was 9° (range 1 - 21°). The subjects were able to follow the instructions in the protocol and performed self-recording of upper arm elevation and velocity., Conclusions: The small difference between the two analyses indicates that recordings performed by employees themselves are comparable, on a group level, with those performed by researchers. Self-recordings in combination with action levels would provide employers with a method for risk assessment as a solid basis for prevention of work-related musculoskeletal disorders.

Background: Echocardiography involves strenuous postures of the upper limbs. This study explored the physical workload in the neck and upper limbs in sonographers performing echocardiography, and the extent to which the workload differs from than in other work tasks (other sonographic examinations, and nonsonographic tasks)., Methods: The physical load was assessed by inclinometry, goniometry, and electromyography methods in 33 female sonographers during authentic work using three different echocardiography techniques and other work tasks., Results: Echocardiography was characterized by low velocities of the head, arms, and wrists, and a low proportion of muscular resting time in the forearms, in the transducer limb, and the computer limb. The transducer limb was more elevated in one of the techniques, but this technique also involved a higher proportion of muscular resting time of the trapezius muscle. We also found a high proportion of awkward wrist postures in the transducer wrist in all three techniques; in one due to prolonged flexion, and in the others due to prolonged extension. Other work tasks were less static, and were performed with higher upper arm and wrist velocities., Conclusion: None of the three echocardiography techniques was optimal concerning physical workload. Thus, to achieve more variation in physical load we recommend that the equipment be arranged so that the sonographer can alternate between two different techniques during the workday. We also propose alternation between echocardiography and nonsonographic tasks, in order to introduce variation in the physical workload. Clinical expertise should be used to achieve further improvements.

[This corrects the article DOI: 10.1155/2016/8085216.].

Background: Wrist disorders are common in force demanding industrial repetitive work. Visual assessment of force demands have a low reliability, instead surface electromyography (EMG) may be used as part of a risk assessment for work-related wrist disorders. For normalization of EMG recordings, a power grip (hand grip) is often used as maximal voluntary contraction (MVC) of the forearm extensor muscles. However, the test-retest reproducibility is poor and EMG amplitudes exceeding 100% have occasionally been recorded during work. An alternative MVC is resisted wrist extension, which may be more reliable., Objective: To compare hand grip and resisted wrist extension MVCs, in terms of amplitude and reproducibility, and to examine the effect of electrode positioning., Methods: Twelve subjects participated. EMG from right forearm extensors, from four electrode pairs, was recorded during MVCs, on three separate occasions., Results: The group mean EMG amplitudes for resisted wrist extension were 1.2-1.7 times greater than those for hand grip. Resisted wrist extension showed better reproducibility than hand grip., Conclusions: The results indicate that the use of resisted wrist extension is a more accurate measurement of maximal effort of wrist extensor contractions than using hand grip and should increase the precision in EMG recordings from forearm extensor muscles, which in turn will increase the quality of risk assessments that are based on these.

Repetitive work and work in constrained postures are risk factors for developing musculoskeletal disorders. Low-cost, user-friendly technical methods to quantify these risks are needed. The aims were to validate inclination angles and velocities of one model of the new generation of accelerometers with integrated data loggers against a previously validated one, and to compare meaurements when using a plain reference posture with that of a standardized one. All mean (n = 12 subjects) angular RMS-differences in 4 work tasks and 4 body parts were <2.5° and all mean median angular velocity differences <5.0 °/s. The mean correlation between the inclination signal-pairs was 0.996. This model of the new generation of triaxial accelerometers proved to be comparable to the validated accelerometer using a data logger. This makes it well-suited, for both researchers and practitioners, to measure postures and movements during work. Further work is needed for validation of the plain reference posture for upper arms., (Copyright © 2016 Elsevier Ltd and The Ergonomics Society. All rights reserved.)

Purpose: To compare the diagnostic accuracy and safety of a 14-gauge core needle versus a 22-gauge fine needle in the evaluation of thoracic lesions by CT-guided percutaneous transthoracic needle biopsy (TTNB)., Materials and Methods: Medical charts of all patients who underwent CT-guided percutaneous transthoracic core-needle biopsies (CNBs) with a 14-gauge Spirotome device (99 patients, 102 procedures) and fine-needle biopsies (FNBs) with a 22-gauge Rotex needle (92 patients, 102 procedures) between 2007 and 2013 at a single academic institution were retrospectively reviewed. Variables that could influence diagnostic accuracy and safety were collected., Results: The overall and cancer-specific diagnostic accuracy rates were 90% and 94%, respectively, with CNB, versus 82% and 89% with FNB. Precise cancer type/subtype was provided by 97% of CNBs versus 65% of FNBs (P < .001). In patients with lung cancer considered for targeted therapy, biomarker analyses were feasible in 80% of CNBs versus 0% of FNBs (P < .001). The rate of pneumothorax was significantly higher with CNB versus FNB (31% vs 19%; P = .004), but chest tube insertion rates were similar (10% vs 11%, respectively). Major bleeding complications occurred in 1% of CNBs versus 2% of FNBs and were associated with one death in the CNB group., Conclusions: Percutaneous transthoracic CNB with a 14-gauge Spirotome needle provided better characterization of cancer lesions and allowed biomarker analyses without a significant increase in major procedural complications., (Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.)

Background: It is usually assumed that musculoskeletal pain is associated with both the physical workload and the psychosocial work environment, as well as with personal and lifestyle factors. This study aims to ascertain the prevalence of musculoskeletal pain in women with varying or different occupational exposures, and to explore the associations between musculoskeletal pain and the occupational and personal factors., Methods: A questionnaire on physical, psychosocial and individual factors was answered by 1591 women in five occupational groups with contrasting occupational exposures (teachers, anaesthetic, theatre, and assistant nurses, and sonographers). The outcome measure was musculoskeletal pain (in a new model based on frequency and intensity of complaints the preceding year) from the neck, shoulders, hands, lower back and feet., Results: Neck pain was equally frequent among teachers, assistant nurses and sonographers, and less frequent in anaesthetic and theatre nurses. The sonographers experienced the highest prevalence of shoulder pain, while the assistant nurses were the most affected in the wrists and hands, lower back, and feet. The teachers reported the highest scores in most of the psychosocial dimensions. The theatre nurses scored highest in strenuous work postures and movements (mechanical exposure index, MEI), and the assistant nurses in physical activity and lifting (physical exposure index, PHYI). Multivariable models in the total population showed that both the physical workload and the psychosocial work environment were associated with pain in all body regions, though different factors affected different regions. Pain in the neck, shoulders, hands and lower back was strongly associated with a high MEI and high job demands, while pain in the feet was associated with a high PHYI and a high BMI. A young age was associated with pain in the neck, and an older age was associated with pain in the hands and feet. Lack of time for personal recovery was associated with pain in the shoulders and lower back., Conclusions: The occupational groups were affected differently and need different protective measures. For the teachers, the psychosocial work environment should be improved. The surgical staff and sonographers require measures to mitigate lifting and constrained postures.

Introduction. We herein report our experience with new fully covered self-expanding metallic stents in the setting of inoperable recurrent benign tracheobronchial stenosis. Methods. Between May 2010 and July 2014, 21 Micro-Tech® FC-SEMS (Nanjing Co., China). were placed in our hospital in 16 patients for inoperable, recurrent (after dilatation), and symptomatic benign airway stenosis. Their medical files were retrospectively reviewed in December 2014, with focus on stent's tolerance and durability data. Results. Twenty-one stents were inserted: 13 for posttransplant left main bronchus anastomotic stricture, seven for postintubation tracheal stenosis, and one for postlobectomy anastomotic stricture. Positioning was easy for all of them. Stents were in place for a mean duration of 282 days. The most common complications were granulation tissue development (35%), migration (30%), and sputum retention (15%). Fifty-five % of the stents (11/20) had to be removed because of various complications, without difficulty for all of them. None of the patients had life-threatening complications. Conclusion. Micro-Tech FC-SEMS were easy to position and to remove. While the rate of complications requiring stent removal was significant, no life-threatening complication occurred. Further studies are needed to better define their efficacy and safety in the treatment of benign airway disease.

Objectives: Endoscopic ultrasonography (EUS) and endobronchial ultrasound-fine-needle aspiration (EBUS-FNA), is an accurate technique for evaluation of mediastinal lymph nodes (MLN) and stadification of lung cancer. The aims of the study are to evaluate the feasibility and the efficacy of the combined technique compared with mediastinoscopy for the diagnosis of MLN., Design and Methods: All patients with suspected malignant MLN and/or lung lesion identified by positron emission tomography-computed tomography underwent combined EUS-EBUS-FNA. The combined procedure was performed in outpatients under general anesthesia for EUS and sedation by intravenous midazolam for EBUS when performed separately, using linear-array echoendoscopes. The MLN were punctured during the EUS and EBUS-FNA procedures with a 22 gauge needle., Results: Thirty-four patients underwent consecutively EUS and EBUS-FNA between September 2011 and November 2013 (8 women, 26 men, mean age of 65.9 year, range: 51-83). Combined EUS-EBUS-FNA was performed in a single time procedure in 26 patients (mean time 50 min) and in two different times in eight patients (mean delay 3 days). Twenty-five malignant and 9 inflammatory lesions were diagnosed. Mediastinoscopy was performed in nine patients and confirmed in eight patients the initial combined EUS-EBUS-FNA diagnosis. The diagnosis was obtained in 91.2% with EUS-FNA, 70.6% with EBUS-FNA and 97% when combined procedure was performed. The overall sensitivity, specificity, positive and negative predictive values of EUS-EBUS-FNA for diagnosing malignancy were 96.5%, 100%, 100% and 90% respectively. No complications related to the procedure were observed., Conclusion: Combined EUS-EBUS-FNA represents an accurate technique in the diagnosis of MLN, can be done in a single time procedure and has the advantage of being less invasive than mediastinoscopy.

Background: Sorting mail into racks for postmen is visually demanding work. This can result in backward inclination of their heads, especially more pronounced for those who use progressive addition lenses., Objective: To evaluate the effects of customized working spectacles on the physical workload of postmen., Methods: Twelve male postmen sorted mail on two occasions: once using their private progressive spectacles and once using customized sorting spectacles with inverted progressive lenses. Postures and movements of the head, upper back, neck, and upper arms were measured by inclinometry. The muscular load of the trapezius was measured by surface electromyography., Results: With the customized sorting spectacles, both the backward inclination of the head and backward flexion of the neck were reduced (3°), as well as the muscular load of the right upper trapezius, compared to sorting with private spectacles. However, with the sorting spectacles, there was a tendency for increased neck forward flexion, and increased sorting time., Conclusion: The reduction in work load may reduce the risk for developing work-related musculoskeletal disorders due to the positive reduction of the backward inclination of the head. But the tendency for increased neck forward flexion may reduce the positive effects. However, the magnitude of the possible reduction is difficult to predict, especially since quantitative data on exposure-response relationships are unknown. Alternative working spectacles with inverted near progressive lenses ought to be evaluated. They should still result in a positive reduced backward inclination of the head and may not cause any increased forward flexion.

Rigid bronchoscopy under general anesthesia enables performing diagnostic and/or therapeutic procedures in the tracheobronchial tree. This technique is characterized by specific technical problems, insofar as the anesthesiologist and the operators share the same space, namely the airway. Several potential complications (hemorrhage inside the airway, threat to ventilation ...) may arise. These challenges render the ability to use the variable available techniques essential, as well as knowledge of the complications they could entail, and the ability to rapidly solve them. General anesthesia is usually total intravenous anesthesia, using short acting agents. Ventilation can be spontaneous, but more often insured using high-frequency jet ventilation. The hospital infrastructure and staff must have the expertise to perform this particular procedure, in order to limit the complication rate.

Introduction: Idiopathic pulmonary fibrosis (IPF) is one of the most frequent interstitial lung disease. Emphysema can be associated with IPF as described in the «Combined pulmonary fibrosis and emphysema» syndrome., Aim: The primary endpoint of this retrospective cohort study was to evaluate the impact of the association of IPF and emphysema on lung function tests parameters (FVC, TLC, FEV1, FEV1/FVC and DLCO). The secondary endpoint was to assess the impact of the associated radiological emphysema on lung function parameters used in the du Bois prognostic score recently developed by Ron du Bois et al., Method: We retrospectively reviewed the medical files of 98 patients with lung fibrosis who were followed in our University Hospital with access to pharmacological studies and lung transplantation from 1981 to 2011. Fifty six patients were considered for analysis. The collected data included gender, age, smoking history and respiratory hospitalizations. We also analysed their pulmonary functional parameters along with radiological characteristics, in particular the presence of emphysema which was assessed on thoracic high resolution CT scan. The du Bois score was retrospectively calculated from these data., Results: TLC and FVC at diagnosis were significantly higher in the IPF-E group compared to the IPF group (respectively 86.6 ± 17.2% pv versus 72.0 ± 15.0% pv; p: 0.004 and 86.8 ± 18.4% pv versus 72.6 ± 20.6% pv; p: 0.020). The [Formula: see text] used in the calculation of the du Bois prognostic score was significantly higher in the IPF-E group. By cons, [Formula: see text] was not statistically different between the two groups., Conclusion: Radiological emphysema associated with IPF had an impact on pulmonary function tests. Despite this difference, the du Bois score was not statistically different between these two groups. Nevertheless, after one year of follow up, the patients with emphysema were in a subclass with a lower mortality rate than those without emphysema., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Disorders in the musculoskeletal system have been associated with a high physical workload as well as psychosocial and individual factors. It is however not obvious which of these factors that is most important to prevent. Musculoskeletal disorders in neck and upper extremity was assessed by interview and clinical examination in 79 teachers and 93 assisting nurses, all females. Psychosocial work environment was assessed by questionnaire. The physical workload was recorded by technical measurements of postures, movements and muscular load, in 9 teachers and 12 nurses. The physical workload was lower among the teachers, but they had a more demanding psychosocial work environment. Among the nurses, but not in the teachers, the neck-shoulder disorders were associated with a high body mass index (BMI). The teachers reported neck-shoulder complaints to a higher extent than the nurses, but had much lower prevalence of diagnoses in the clinical examination (12% vs. 25%; POR 0.3 CI 0.1 - 1.2; adjusted for age and BMI). The results suggest that adverse psychosocial conditions among the teachers give rise to a different kind of pain in the neck-shoulder region than from physical overload, troublesome but not as severe as the one afflicting the nurses.

This study was performed between 2004 and 2011 at mail sorting facilities in Sweden. During this time, different interventions were performed. The first was a lighting intervention that had a positive impact on the postal workers, especially those with eyestrain. A new lighting system also improved the illuminance and gave better light distribution. The second intervention involved new personal spectacles for the postal workers who needed them and this had a positive effect on eyestrain. The third intervention involved a specific type of sorting spectacles for the postal workers who already used progressive lenses privately. The reading distances that the postal workers had while sorting the mail was inverted to the distances in their regular progressive lenses. The new sorting spectacles had a positive effect on head postures and on muscular activity.

beta-Secretase (BACE) is an aspartyl protease, which proteolytically processes amyloid precursor protein, making BACE an interesting pharmacological target in Alzheimer's disease. To study the enzymatic function of BACE, we mutated either of the two aspartic acid residues in the active site of BACE. This rendered BACE functionally inactive without affecting the degree of glycosylation or endosomal localization. In contrast, substituting both active site aspartic acid residues produced a functionally inactive, endoplasmic reticulum-retained and partially glycosylated BACE. Interestingly, co-expression of the two single active site mutants partially restored beta-site cleavage of amyloid precursor protein, and the restored activity was inhibited with similar dose-dependency and potency as wildtype BACE by a small molecule inhibitor raised against BACE. In sum, our data suggest that two different active site mutants can complement each other in a partially functional BACE dimer and mediate APP processing., (Copyright 2010 Elsevier Inc. All rights reserved.)

Introduction: FOLFOX 4 chemotherapy (5-fluorouracil, leucovorin and oxaliplatin) is the standard adjuvant treatment for stage III colon cancer. The principal secondary effects described are haematological, gastro-intestinal or neurological. A single case of obliterative bronchiolitis with organising pneumonia has been described recently., Case Report: We report the case of a female patient aged 74 years who, after 12 courses of FOLFOX 4 chemotherapy, developed acute onset of severe shortness of breath and a dry cough but remained afebrile. A thoracic CT-scan showed symmetrical bilateral interstitial infiltration that was reticular in appearance, and predominantly basal and peripheral in distribution. Broncho-alveolar lavage revealed an alveolitis with 9% eosinophils and 4% neutrophils. Transbronchial biopsies showed the appearances of obliterative bronchiolitis with organising pneumonia. Systemic corticosteroid treatment led to a remarkable clinical and functional improvement., Conclusion: To our knowledge, this is the second case of obliterative bronchiolitis with organising pneumonia that has been described following adjuvant treatment based on FOLFOX 4.

We describe the case of a 76-year-old male presenting a thrombocytopenia at the diagnosis of Hodgkin disease. Basing on bone marrow biopsy and evolution, we diagnosed an immune thrombocytopenia and treated with intravenous gammaglobulins. The platelet count normalized in a few days under this therapy. Immune thrombocytopenia purpura (ITP) is a rare complication of Hodgkin disease (HD). It seems to be due to the production of antibodies directed against platelet membrane proteins. The patient's and the lymphoma's characteristics are not predictive for it to happen. The evolution of HD is also not influenced by its occurrence. Various treatments (including corticoids and immunomodulating agents) have been tried with different efficiencies.

Inhibition of Notch signaling by Numb is critical for many cell fate decisions. In this study, we demonstrate a more complex relationship between Notch and the two vertebrate Numb homologues Numb and Numblike. Although Numb and Numblike at low levels of Notch signaling negatively regulated Notch, high levels of Notch signaling conversely led to a reduction of Numb and Numblike protein levels in cultured cells and in the developing chick central nervous system. The Notch intracellular domain but not the canonical Notch downstream proteins Hes 1 and Hey 1 caused a reduction of Numb and Numblike. The Notch-mediated reduction of Numblike required the PEST domain in the Numblike protein and was blocked by the proteasome inhibitor MG132. Collectively, these observations reveal a reciprocal negative regulation between Notch and Numb/Numblike, which may be of relevance for stabilizing asymmetric cell fate switches and for tumor development.

Background: Prolonged labour is associated with greater morbidity and mortality for mother and child. Connexin 43 is a major myometrial gap junction protein found in human myometrium. Syndecan 3 seems to prevail in the human uterus among heparan sulphate proteoglycans, showing the most significant increase during labour. The aims of the present study were to investigate syndecan 3 and connexin 43 mRNA expressions and protein distributions in human uterine tissue during normal and prolonged labour., Methods: Uterine isthmic biopsies were collected from non-pregnant (n = 7), term pregnant women not in labour (n = 14), in normal labour (n = 7) and in prolonged labour (n = 7). mRNA levels of syndecan 3 and connexin 43 were determined by real time RT-PCR. The localization and expression were demonstrated by immunohistochemistry and confocal microscopy., Results: In women with prolonged labour, the mRNA expressions of syndecan 3 and Connexin 43 were considerably lower than the expression level at normal labour (p < 0.05). In term-pregnant tissue, the expression of syndecan 3 and connexin 43 did not differ significantly compared to non-pregnant and normal labour. The immunoreactivity of syndecan 3 was strong at normal labour, in contrast to prolonged labour, where both a weaker expression and an irregular distribution were detected. The immunoreactivity of connexin 43 increased until term and further stronger staining occurred at normal labour. At prolonged labour, the immunoreactivity was weaker and more unevenly distributed. At labour, a co-localization of syndecan 3 and connexin 43 could be demonstrated in the smooth muscle by confocal microscopy., Conclusion: The high expression of syndecan 3 and connexin 43 and their co-localization to the smooth muscle bundles during normal labour, together with the significant reduction in prolonged labour, may indicate a role for these proteins in the co-ordination of myometrial contractility.

Background: Activated fibroblasts, which have previously been obtained from bronchoalveolar lavage fluid (BALF), are proposed to be important cells in the fibrotic processes of asthma and scleroderma (SSc). We have studied the motility for BALF derived fibroblasts in patients with SSc that may explain the presence of these cells in the airway lumen. Furthermore, we have compared phenotypic alterations in activated fibroblasts from BALF and bronchial biopsies from patients with mild asthma and SSc that may account for the distinct fibrotic responses., Methods: Fibroblasts were cultured from BALF and bronchial biopsies from patients with mild asthma and SSc. The motility was studied using a cell migration assay. Western Blotting was used to study the expression of alpha-smooth muscle actin (alpha-SMA), ED-A fibronectin, and serine arginine splicing factor 20 (SRp20). The protein expression pattern was analyzed to reveal potential biomarkers using two-dimensional electrophoresis (2-DE) and sequencing dual matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-TOF). The Mann-Whitney method was used to calculate statistical significance., Results: Increased migration and levels of ED-A fibronectin were observed in BALF fibroblasts from both groups of patients, supported by increased expression of RhoA, Rac1, and the splicing factor SRp20. However, these observations were exclusively accompanied by increased expression of alpha-SMA in patients with mild asthma. Compared to BALF fibroblasts in mild asthma, fibroblasts in SSc displayed a differential protein expression pattern of cytoskeletal- and scavenger proteins. These identified proteins facilitate cell migration, oxidative stress, and the excessive deposition of extracellular matrix observed in patients with SSc., Conclusion: This study demonstrates a possible origin for fibroblasts in the airway lumen in patients with SSc and important differences between fibroblast phenotypes in mild asthma and SSc. The findings may explain the distinct fibrotic processes and highlight the motile BALF fibroblast as a potential target cell in these disorders.

Deposition of amyloid beta-peptide (Abeta) into amyloid plaques is one of the invariant neuropathological features of Alzheimer's disease. Proteins that codeposit with Abeta are potentially important for the pathogenesis, and a recently discovered plaque-associated protein is the collagenous Alzheimer amyloid plaque component (CLAC). In this study, we investigated the molecular interactions between Abeta aggregates and CLAC using surface plasmon resonance spectroscopy and a solid-phase binding immunoassay. We found that CLAC binds to Abeta with high affinity, that the central region of Abeta is necessary and sufficient for CLAC interaction, and that the aggregation state of Abeta as well as the presence of negatively charged residues is important. We also show that this binding results in a reduced rate of fibril elongation. Taken together, we suggest that CLAC becomes involved at an intermediate stage in the pathogenesis by binding to Abeta fibrils, including fibrils formed from peptides with truncated N- or C-termini, and thereby slows their growth.

Recently, a novel plaque-associated protein, collagenous Alzheimer amyloid plaque component (CLAC), was identified in brains from patients with Alzheimer's disease. CLAC is derived from a type II transmembrane collagen precursor protein, termed CLAC-P (collagen XXV). The biological function and the contribution of CLAC to the pathogenesis of Alzheimer's disease and plaque formation are unknown. In vitro studies indicate that CLAC binds to fibrillar, but not to monomeric, amyloid beta-peptide (Abeta). Here, we examined the effects of CLAC on Abeta fibrils using assays based on turbidity, thioflavin T binding, sedimentation analysis, and electron microscopy. The incubation of CLAC with preformed Abeta fibrils led to increased turbidity, indicating that larger aggregates were formed. In support of this contention, more Abeta was sedimented in the presence of CLAC, as determined by gel electrophoresis. Moreover, electron microscopy revealed an increased amount of Abeta fibril bundles in samples incubated with CLAC. Importantly, the frequently used thioflavin T-binding assay failed to reveal these effects of CLAC. Digestion with proteinase K or trypsin showed that Abeta fibrils, incubated together with CLAC, were more resistant to proteolytic degradation. Therefore, CLAC assembles Abeta fibrils into fibril bundles that have an increased resistance to proteases. We suggest that CLAC may act in a similar way in vivo.