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The COVID-19 pandemic identified an urgent need to re-evaluate the provision of spirometry for clinical monitoring. Home spirometry offers the opportunity for real-time disease evaluation without risk of nosocomial infection. To determine the utility of home spirometry in interstitial lung disease (ILD), interim data from the ongoing INJUSTIS study was evaluated. High correlation was observed between home and hospital spirometry at baseline(r=0.89) and three-months(r=0.82). Over 90% of home spirometry values were within Bland-Altman agreement limits at both time points, although frequently underestimated hospital values. Home spirometry is feasible in people with fibrotic ILD.

Background The adherence to and clinical efficacy of pulmonary rehabilitation in idiopathic pulmonary fibrosis (IPF), particularly in comparison to people with chronic obstructive pulmonary disease (COPD), remains uncertain. The objectives of this real-world study were to compare the responses of patients with IPF with a matched group of patients with COPD undergoing the same supervised, outpatient pulmonary rehabilitation program, and to determine whether pulmonary rehabilitation is associated with survival in IPF. Research question Do people with IPF improve to the same extent with pulmonary rehabilitation as a matched group of individuals with COPD, and are non-completion of and/or non-response to pulmonary rehabilitation associated with one-year all-cause mortality in IPF? Study design and methods Using propensity score matching, 163 patients with IPF were matched 1:1 with a control group of 163 patients with COPD referred to pulmonary rehabilitation. We compared between-group pulmonary rehabilitation completion rates and response. Survival status in the IPF cohort was recorded over one-year following pulmonary rehabilitation discharge. Cox proportional-hazards regression explored the association between pulmonary rehabilitation status and all-cause mortality. Results Similar pulmonary rehabilitation completion rates (IPF: 69%; COPD: 63%; p=0.24) and improvements in exercise response were observed in both groups with no significant mean (95% confidence interval (CI)) between-group differences in incremental shuttle walk (ISW) change (2 (-18 to 22) meters). Pulmonary rehabilitation non-completion (hazard ratio (HR) (95%CI) 5.62 (2.24 to 14.08)) and non-response (HR (95%CI) 3.91 (1.54 to 9.93)) were independently associated with increased one-year all-cause mortality in IPF. Interpretation Compared with a matched group of patients with COPD, this real-word study demonstrates that patients with IPF have similar completion rates and magnitude of response to pulmonary rehabilitation. In IPF, non-completion of and non-response to pulmonary rehabilitation were associated with increased all-cause mortality. These data reinforce the benefits of pulmonary rehabilitation in patients with IPF.

Background and aims: Computed tomography (CT), often more accessible than magnetic resonance imaging (MRI), remains widely used though radiation exposure is an obvious disadvantage. We previously showed that modern CT technology can achieve over 70% reduction in radiation-dose without loss of accuracy. Here, we compare low- versus conventional-dose CT in patients with known Crohn's disease to assess clinical confidence and accuracy of the low-dose procedure in the semi-acute setting.Methods: A comparative study of low-dose CT with full iterative reconstruction (IR) versus conventional-dose CT was conducted in 50 consecutive outpatients with Crohn's disease. Clinicians were provided with the low-dose images and reports, whereas conventional-dose images were reviewed after 4 weeks.Results: The clinical question was adequately addressed with low-dose IR imaging in all cases. Complications of Crohn's were detected in 37/50 (74%) with no disagreement between low- and conventional-dose imaging. The effective radiation dose reduction was 76.5% (low-dose mean 2.15 mSv versus conventional-dose CT 6.99 mSv).Conclusion: Low-dose IR CT is safe and accurate for evaluating distribution and complications of known Crohn's disease in the outpatient setting. We propose that low-dose radiation imaging should be adopted as standard-of-care for the evaluation of Crohn's disease and an acceptable alternative to MR particularly in the acute setting. ClinicalTrials.gov: NCT03140306.

BACKGROUND The diagnosis of glioblastoma (GBM) in infants aged ≤ 1 year is extremely rare, and its comparability to the more common adult diagnosis is underexplored. Correspondingly, the objective of this study was to interrogate a national cancer database to elucidate the typical survival and clinical profile of this demographic. METHODS All GBM patients aged ≤ 1 year in the U.S. National Cancer Database (NCDB) between 2005 and 2016 were retrospectively reviewed. Data were summarized, and overall survival (OS) was modeled using Kaplan-Meier and Cox regression analyses. RESULTS A total of 86 patients satisfied criteria for entry into study, making up 0.08% of all GBM diagnoses in the database. There were 32 (37%) females and 54 (63%) males. Irrespective of treatment, median OS was 67.3 months (95% CI, 46-91), which was distinct from all other ages and pediatric age groups. There were 74 (86%) treated by surgery, 51 (59%) treated by chemotherapy, and 17 (20%) treated by radiation therapy. Multivariable analysis demonstrated that Hispanic status (HR = 3.41, P = 0.02) and the presence of comorbidity (HR = 3.24, P = 0.01) independently predicted shorter OS, whereas treatment with chemotherapy (HR = 0.18, P

PURPOSE Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals. PATIENTS AND METHODS Data were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium. Tumor spectrum, efficacy of the surveillance protocol, and malignant transformation of low-grade lesions were examined for the entire cohort. Survival outcomes were analyzed for patients followed prospectively from the time of surveillance implementation. RESULTS A total of 193 malignant tumors in 110 patients were identified. Median age of first cancer diagnosis was 9.2 years (range: 1.7-39.5 years). For patients undergoing surveillance, all GI and other solid tumors, and 75% of brain cancers were detected asymptomatically. By contrast, only 16% of hematologic malignancies were detected asymptomatically ( P < .001). Eighty-nine patients were followed prospectively and used for survival analysis. Five-year overall survival (OS) was 90% (95% CI, 78.6 to 100) and 50% (95% CI, 39.2 to 63.7) when cancer was detected asymptomatically and symptomatically, respectively ( P = .001). Patient outcome measured by adherence to the surveillance protocol revealed 4-year OS of 79% (95% CI, 54.8 to 90.9) for patients undergoing full surveillance, 55% (95% CI, 28.5 to 74.5) for partial surveillance, and 15% (95% CI, 5.2 to 28.8) for those not under surveillance ( P < .0001). Of the 64 low-grade tumors detected, the cumulative likelihood of transformation from low-to high-grade was 81% for GI cancers within 8 years and 100% for gliomas in 6 years. CONCLUSION Surveillance and early cancer detection are associated with improved OS for individuals with CMMRD.

Background: In the past two decades, many advances have been made to our understanding of interstitial lung disease (ILD) and the way we approach its treatment. Despite this, many questions remain unanswered, particularly those related to how the disease and its therapies impact outcomes that are most important to patients. There is currently a lack of guidance on how to best define and incorporate these patient-centered outcomes in ILD research. Objectives: To summarize the current state of patient-centered outcomes research in ILD, identify gaps in knowledge and research, and highlight opportunities and methods for future patient-centered research agendas in ILD. Methods: An international interdisciplinary group of experts was assembled. The group identified top patient-centered outcomes in ILD, reviewed available literature for each outcome, highlighted important discoveries and knowledge gaps, and formulated research recommendations. Results: The committee identified seven themes around patient-centered outcomes as the focus of the statement. After a review of the literature and expert committee discussion, we developed 28 research recommendations. Conclusions: Patient-centered outcomes are key to ascertaining whether and how ILD and interventions used to treat it affect the way patients feel and function in their daily lives. Ample opportunities exist to conduct additional work dedicated to elevating and incorporating patient-centered outcomes in ILD research.

Rationale: There is an urgent need for simple, cost-effective prognostic biomarkers for idiopathic pulmonary fibrosis (IPF); biomarkers that show potential include monocyte count. Objectives: We used pooled data from pirfenidone and interferon gamma-1b trials to explore the association between monocyte count and prognosis in patients with IPF. Methods: This retrospective pooled analysis included patients (active and placebo arms) from four Phase III, randomized, placebo-controlled trials: ASCEND (NCT01366209), CAPACITY (NCT00287729 and NCT00287716), and INSPIRE (NCT00075998). Outcomes included IPF progression (≥10% absolute decline in percent predicted forced vital capacity, ≥50 m decline in 6-minute walk distance, or death), all-cause hospitalization, and all-cause mortality over 1 year. The relationship between monocyte count (defined as time-dependent) and outcomes was assessed using bivariate and multivariable models. Measurements and Main Results: This analysis included 2067 patients stratified by monocyte count (at baseline

Background Idiopathic pulmonary fibrosis (IPF) is a progressive debilitating lung disease with considerable morbidity. Heterogeneity in epidemiologic studies means the full impact of the disease is unclear. Methods A targeted literature search for population-based, observational studies reporting incidence and/or prevalence of IPF from January 2009 to April 2020 was conducted. Identified studies were aggregated by country. For countries with multiple publications, a weighted average was determined. Incidence and prevalence data were adjusted for between-study differences where possible. The final model included adjusted estimates of incidence and prevalence per 10,000 of the population with 95% confidence intervals. As prevalence estimates vary depending on the definitions used, estimates were based on a specific case definition of IPF. Results Overall, 22 studies covering 12 countries met the inclusion criteria, with 15 reporting incidence and 18 reporting prevalence estimates. The adjusted incidence estimates (per 10,000 of the population) ranged from 0.35 to 1.30 in Asia–Pacific countries, 0.09 to 0.49 in Europe, and 0.75 to 0.93 in North America. Unadjusted and adjusted incidence estimates were consistent. The adjusted prevalence estimates ranged from 0.57 to 4.51 in Asia–Pacific countries, 0.33 to 2.51 in Europe, and 2.40 to 2.98 in North America. South Korea had the highest incidence and prevalence estimates. When prevalence estimates were compared to country-specific rare disease thresholds, IPF met the definition of a rare disease in all countries except South Korea. There were notable geographic gaps for IPF epidemiologic data. Conclusions Due to differences in study methodologies, there is worldwide variability in the reported incidence and prevalence of IPF. Based on the countries included in our analysis, we estimated the adjusted incidence and prevalence of IPF to be in the range of 0.09–1.30 and 0.33–4.51 per 10,000 persons, respectively. According to these prevalence estimates, IPF remains a rare disease. For consistency, future epidemiologic studies of IPF should take age, sex, smoking status, and the specificity of case definitions into consideration.

Obstructive sleep apnea (OSA) is a prevalent disorder that has direct correlation to cardiovascular disease. Understanding the etiology and symptoms of this condition as it relates to cardiovascular disease can improve comprehensive health assessments and determine the use of appropriate screening tools. This case-based approach follows a patient through assessment, diagnosis, and treatment options. Although lifestyle behavior changes are recommended for all patients, other options, such as positive airway pressure therapy, oral appliances, implantable therapy, surgery, and pharmacological and oxygen therapies, exist and should be explored as treatment options. Yearly follow-up provides the best method for long-term treatment success. Treatment of OSA reduces the incidence of cardiac comorbidities and improves cardiovascular health.

Background The aim of this study was to examine the association between hypertensive disorders of pregnancy (HDP) and behavioural outcomes in offspring at five time-points. Methods We used maternal-reported data from the Millennium Cohort Study. Data on HDP were collected when children were 9-months. Data on behavioural outcomes were collected at age 3, 5, 7, 11 and 14years using the Strengths and Difficulties Questionnaire (SDQ). Multivariate logistic regression analysis examined a HDP-behavioural difficulties relationship, using validated SDQ cut-off points. Multilevel models with linear splines examined the association between HDP and repeated measures of SDQ. Results 18,274 singleton children were included in the study at baseline, Multivariate logistic regression suggested HDP was not significantly associated with SDQ domain cut-off points at ages 3, 7 and 11years. At age 5years, HDP was associated with a 40% increased odds of behavioural difficulties based on total SDQ(≥17) (OR:1.40, 95% CI:1.03,1.91). HDP was associated with a 43% increased odds of Peer Problem difficulties at age 5 (OR:1.43, 95% CI:1.10,1.86), and a 28% increased odds of Peer Problem difficulties(≥4) at age 14 (OR:1.28, 95% CI:1.02,1.61). In the linear spline model, mean SDQ score was higher at each time-point in those exposed to HDP, although did not always reach statistical significance. Limitations Data on different classifications of HDP were unavailable; therefore, we could not examine the effect of gestational hypertension and preeclampsia separately. Conclusions While we did not find strong evidence of associations between HDP and behavioural outcomes overall, some associations between HDP and behavioural difficulties did persist at age 5 and 14years.

Thoracic computed tomography (CT) is the imaging reference method in the diagnosis, assessment and management of lung disease. In the setting of cystic fibrosis (CF), CT demonstrates increased sensitivity compared with pulmonary function tests and chest radiography, and findings correlate with clinical outcomes. Better understanding of the aetiology of CF lung disease indicates that even asymptomatic infants with CF can have irreversible pulmonary pathology. Surveillance and early diagnosis of lung disease in CF are important to preserve lung parenchyma and to optimise long-term outcomes. CF is associated with increased cumulative radiation exposure due to the requirement for repeated imaging from a young age. Radiation dose optimisation, important for the safe use of CT in children with CF, is best achieved in a team environment where paediatric radiologists work closely with paediatric respiratory physicians, physicists and radiography technicians to achieve the best patient outcomes. Despite the radiation doses incurred, CT remains a vital imaging tool in children with CF. Radiologists with special interests in CT dose optimisation and respiratory disease are key to the appropriate use of CT in paediatric imaging. Paediatric radiologists strive to minimise radiation dose to children whilst providing the best possible assessment of lung disease.

In recent decades, aquaculture has played a significant role in fulfilling the vast demand for animal protein requirements and consequently in food security. However, environmental contamination and disease prevalence are considered essential challenges for the sector. In this regard, new approaches have been paved in technology to deal effectively with such challenges. Among these, nanotechnology-as a novel and innovative tool-has a broad spectrum of uses and a tremendous potential in aquaculture and seafood preservation. It can provide new technologies for management of drugs as liberation of vaccines and therefore hold the assurance for civilized protection of farmed fish against disease-causing pathogens. This article presents a review of nanotechnology and its applications in aquaculture. Additionally, it gives a brief idea about the fish disease and classical ways of controlling pathogens. On the other hand, this review sheds the light on nanotechnology as a potential novel tool which may possibly enhance the management and the control of disease prevalence. Therefore, the importance of this technology to promote sustainable aquaculture has also been highlighted. Focusing on the role of selenium nanoparticles as an efficient element is discussed also in this article.

Introduction This study investigates instances of elevated radiation dose on a radiation tracking system to determine their aetiologies. It aimed to investigate the impact of radiographer feedback on these alerts. Methods Over two six-month periods 11,298 CT examinations were assessed using DoseWatch. Red alerts (dose length products twice the median) were identified and two independent reviewers established whether alerts were true (unjustifiable) or false (justifiable). During the second time period radiographers used a feedback tool to state the cause of the alert. A Chi–Square test was used to assess whether red alert incidence decreased following the implementation of radiographer feedback. Results There were 206 and 357 alerts during the first and second time periods, respectively. These occurred commonly with CT pulmonary angiography, brain, and body examinations. Procedural documentation errors and patient size accounted for 57% and 43% of false alerts, respectively. Radiographer feedback was provided for 17% of studies; this was not associated with a significant change in the number of alerts, but the number of true alerts declined (from 7 to 3) (χ2 = 4.14; p = 0.04). Conclusion Procedural documentation errors as well as patient-related factors are associated with false alerts in DoseWatch. Implementation of a radiographer feedback tool reduced true alerts. Implications for practice The implementation of a radiographer feedback tool reduced the rate of true dose alerts. Low uptake with dose alert systems is an issue; the workflow needs to be considered to address this.

Diagnosing the aetiology of interstitial lung disease (ILD) may require histology via a surgical lung biopsy (SLB). SLB is associated with significant complications. Transbronchial lung cryobiopsy (TBLC) can provide large, adequate biopsies with fewer complications offering a potential alternative to SLB. This study evaluated the safety, diagnostic yield and impact of TBLC on diagnostic certainty in the multidisciplinary diagnosis (MDD) of ILD within routine clinical practice. A retrospective study of all TBLC performed in a tertiary institute from March 2014 to December 2016 was performed. Procedures were performed using a flexible bronchoscope and cryoprobe without fluoroscopic guidance. One hundred procedures were performed on 85 patients. A total of 272 cryobiopsies were obtained with a mean biopsy diameter of 5.9 ± 3.2 mm. Ninety-seven percent contained alveolated lung tissue. Diagnosis based against MDD gold standard was confirmed using TBLC in 67.1% of patients and in 72/100 procedures. Three patients proceeded to SLB. The addition of histological information changed the clinic-radiological diagnosis in twelve patients. The most common diagnosis based on clinical-radiologic-pathologic correlation at MDD was idiopathic pulmonary fibrosis (IPF) (51.2%) and hypersensitivity pneumonitis (15.9%). Moderate bleeding occurred in 18% of cases and five patients (5%) developed pneumothorax requiring intervention. Eleven patients required admission, with a mean length of stay of 1.3 ± 0.9 days. TBLC aids the diagnosis of ILD in the appropriate patient and may be an acceptable alternative to SLB with fewer complications. Further work on standardizing the procedure is required.

Background and objective The course of systemic sclerosis-associated interstitial lung disease (SSc-ILD) is highly variable, and accurate prognostic markers are needed. KL-6 is a mucin-like glycoprotein (MUC1) expressed by type II pneumocytes, while CYFRA 21-1 is expressed by alveolar and bronchiolar epithelial cells. Both are released into the blood from cell injury. Methods Serum KL-6 and CYFRA 21-1 levels were measured in a retrospective (n = 189) and a prospective (n = 118) cohort of SSc patients. Genotyping of MUC1 rs4072037 was performed. Linear mixed-effect models were used to evaluate the relationship with change in lung function parameters over time, while association with survival was evaluated with Cox proportional hazard analysis. Results In both cohorts, KL-6 and CYFRA 21-1 were highest in patients with lung involvement, and in patients with extensive rather than limited ILD. KL-6 was higher in patients carrying the MUC1 rs4072037 G allele in both cohorts. In patients with SSc-ILD, serum KL-6, but not CYFRA 21-1, was significantly associated with DLCO decline in both cohorts (P = 0.001 and P = 0.004, respectively), and with FVC decline in the retrospective cohort (P = 0.005), but not the prospective cohort. When combining the cohorts and subgrouping by severity (median CPI = 45.97), KL-6 remained predictive of decline in DLCO in both milder (P = 0.007) and more severe disease (P = 0.02) on multivariable analysis correcting for age, gender, ethnicity, smoking history and MUC1 allele carriage. Conclusion Our results suggest serum KL-6 predicts decline in lung function in SSc, suggesting its clinical utility in risk stratification for progressive SSc-ILD.

Atypical teratoid/rhabdoid tumor (ATRT) is a rare and largely pediatric diagnosis, with poor survival. Diagnosis below the age of 3 years is characteristically seen as a poor prognostic sign. However, elucidating if clinical differences exist within this niche age group has never been attempted before. Correspondingly, we sought to characterize clinical profile of ATRT diagnoses before the age of 3 years based on separate ages of diagnosis. All pediatric ATRT patients aged < 3 years in the US National Cancer Database (NCDB) between 2005 and 2016 were retrospectively reviewed. Age groups were divided based on diagnoses at ages 0–1 years in group 1, 1–2 years in group 2, and 2–3 years in group 3. Data were summarized, and overall survival (OS) was modeled using Kaplan–Meier and Cox regression analyses. A total of 354 ATRT diagnoses were made before the age of 3 years, with surgery used in 316 (89%) cases, chemotherapy in 242 (68%) cases, and radiation therapy in 118 (33%) cases. In terms of diagnosis age, there were 153 (43%) in group 1, 137 (39%) in group 2, and 64 (18%) in group 3. With respect to OS, median value was 9.9 months in group 1, 28.4 months in group 2, and 15.9 months in group 3. Upon multivariate analysis, receiving radiation therapy was the only parameter shared amongst all three groups as independently prognostic of longer OS (HR 0.53, P = 0.01 in group 1; HR 0.34, P < 0.01 in group 2; HR 0.31, P < 0.01 in group 3). In group 1, surgery (HR 0.47, P < 0.01) and chemotherapy (HR 0.44, P < 0.01) were also independently prognostic of longer OS. In group 3, multiple socioeconomic parameters were identified to independently predict longer OS. There were no additional predictive parameters identified in group 2. Although ATRT diagnosed before the age of 3 is typically viewed a poor prognostic age category, our findings demonstrate that the clinical profile of this pediatric niche is highly heterogeneous based on age of diagnosis. Survival of only those diagnosed between 0 and 1 years is independently prognosticated by all three treatment modalities; patients diagnosed between 1 and 2 years trend towards longest survival, and socioeconomic parameters are most influential in those diagnosed between 2 and 3 years.

Background In cohort studies of pulmonary sarcoidosis, abnormal ventilatory patterns have generally been subdivided into restrictive and obstructive defects. Mixed ventilatory defects have largely been overlooked in pulmonary sarcoidosis, as total lung capacity has seldom been taken into account in historical series. Research Question This study evaluated the prevalence of mixed disease in pulmonary sarcoidosis and its clinical associations. Study Design and Methods In patients with pulmonary sarcoidosis (N = 1,110), mixed defects were defined according to American Thoracic Society/European Respiratory Society criteria. Clinical data, pulmonary function variables, and vital status were abstracted from clinical records. Chest radiographs were evaluated independently by two experienced radiologists. Results The prevalence of a mixed ventilatory defect was 10.4% in the whole cohort, rising to 25.9% in patients with airflow obstruction. Compared with isolated airflow obstruction, mixed defects were associated with lower diffusing lung capacity for carbon monoxide levels (50.7 ± 16.3 vs 70.8 ± 18.1; P Interpretation Mixed disease is present in approximately 25% of patients with pulmonary sarcoidosis and airflow obstruction and is associated with lower diffusing lung capacity for carbon monoxide levels, a higher prevalence of stage IV disease, and higher mortality than seen in a pure obstructive defect. These observations identify a distinct phenotype associated with a mixed ventilatory defect, justifying future studies of its clinical and pathogenetic significance.

Increasing integration of computed tomography (CT) into routine patient care has escalated concerns regarding associated radiation exposure. Specific patient cohorts, particularly those with cystic fibrosis (CF) and Crohn's disease, have repeat exposures and thus have an increased risk of high lifetime cumulative effective dose exposures. Thoracic CT is the gold standard imaging method in the diagnosis, assessment and management of pulmonary disease. In the setting of CF, CT demonstrates increased sensitivity compared with pulmonary function tests and chest radiography. Furthermore, in specific cases of Crohn's disease, CT demonstrates diagnostic superiority over magnetic resonance imaging (MRI) for radiological evaluation. Low dose CT protocols have proven beneficial in the evaluation of CF, Crohn's disease and renal calculi, and in the follow up of testicular cancer patients. For individuals with chronic conditions warranting frequent radiological follow up, the focus must continue to be the incorporation of appropriate CT use into patient care. This is of particular importance for the paediatric population who are most susceptible to potential radiation induced malignancy. CT technological developments continue to focus on radiation dose optimisation. This article aims to highlight these advancements, which prioritise the acquisition of diagnostically satisfactory images with the least amount of radiation possible.

The αvβ6 integrin plays a key role in the activation of transforming growth factor-β (TGFβ), a pro-fibrotic mediator that is pivotal to the development of idiopathic pulmonary fibrosis (IPF). We identified a selective small molecule αvβ6 RGD-mimetic, GSK3008348, and profiled it in a range of disease relevant pre-clinical systems. To understand the relationship between target engagement and inhibition of fibrosis, we measured pharmacodynamic and disease-related end points. Here, we report, GSK3008348 binds to αvβ6 with high affinity in human IPF lung and reduces downstream pro-fibrotic TGFβ signaling to normal levels. In human lung epithelial cells, GSK3008348 induces rapid internalization and lysosomal degradation of the αvβ6 integrin. In the murine bleomycin-induced lung fibrosis model, GSK3008348 engages αvβ6, induces prolonged inhibition of TGFβ signaling and reduces lung collagen deposition and serum C3M, a marker of IPF disease progression. These studies highlight the potential of inhaled GSK3008348 as an anti-fibrotic therapy., The αvβ6 integrin is key in activating the pro-fibrotic cytokine TGFβ in idiopathic pulmonary fibrosis. Here, the authors show an inhaled small molecule αvβ6 inhibitor GSK3008348 induces prolonged inhibition of TGFβ signaling pathways in human and murine models of lung fibrosis via αvβ6 degradation.

Background: Measurement of transverse diameter of the Common Bile Duct (CBD) was performed in several studies by Ultrasonography (US) and magnetic resonance imaging using Magnetic Resonance Cholangiopancreatography (MRCP). The size of the extrahepatic bile duct increases with age which should be taken into consideration by the surgeons during the surgery of the gallbladder, pancreas and duodenum. US plays a crucial role in the initial imaging work-up of a patient with jaundice. Because a dilated extrahepatic duct distinguishes obstructive from non-obstructive causes of jaundice. The size of the bile duct is considered to increase normally with age as proved by various studies especially MRCP which is more accurate than US. Aim of Study: The aim of the present work is to demon-strate anatomical variation concerning assessment of transverse diameter of CBD both in adult and geriatric age groups without biliary or hepatic manifestations and detection of age related changes in CBD as one of the causes of non obstructive biliiary dilatation. Material and Methods: The patients were divided into three groups according to their age: 1- Group I: 21-40 years. 2- Group II: 41-60 years, 3- Group III: Over 60 years. Ultra-sound and MRCP techniques were used in this study to assess the diameter of CBD in different age groups. Results: Group I: In US: In this age group the mean of the widest transverse diameter of extrahepatic bile duct was 0.25 with a range: 0.18-0.41. In males the mean was: 0.23 with a range: 0.19-0.26. In females: The mean was: 0.28 with a range: 0.18-0.41. In MRCP: In this age group the mean of the widest transverse diameter of extrahepatic bile duct was 37.5 with a range: 21-49. In males: The mean was: 36 with a range: 21-46. In females: The mean was: 40 with a range: 0.29-49. Group II: In US: The mean of the widest transverse diameter of extrahepatic bile duct was 0.32 with a range: 0.19-0.41. In males: The mean was: 0.31 with a range: 0.19- 0.39. In females: The mean was: 0.33 with a range: 0.27-0.41. In MRCP: The mean of the widest transverse diameter of extrahepatic bile duct was 46.5 with a range: 24-62. In males: The mean was: 52.6 with a range: 41-62. In females: The mean was: 40.4 with a range: 0.24-51. Group III: In US: The mean of the widest transverse diameter of extrahepatic bile duct was 0.40 with a range: 0.26-0.63. In males: The mean was: 0.39 with a range: 0.28-0.52. In females: The mean was: 0.42 with a range: 0.26-0.63. In MRCP: The mean of the widest transverse diameter of extrahepatic bile duct was 88.31 with a range: 49-180. In males: The mean was: 94.27 with a range: 69-170. In females: The mean was: 81.93 with a range: 49-180. Conclusion: Both US and MRCP modalities revealed that the widest transverse diameter of CBD increases with age.

Background: Type 2 diabetes mellitus is an expanding health problem. Binary antidiabetic combinations of Metformin Hydrochloride (MET) with either Saxagliptin Hydrochloride (SAX), or Dapagliflozin (DAP) are widely used. Review of the literature revealed that no single HPTLC method has been reported for the simultaneous determination of MET, SAX, and DAP allowing the determination of binary mixtures of any two of the three cited drugs in their tablets using the same experimental conditions, an important advantage for quality control. The advantages of HPTLC method relies on the simultaneous analysis of a large number of samples in a shorter analysis time, less solvent consumption, and less expenses, compared with HPLC. Objective: The objective of the proposed method is to develop and validate a single and simple HPTLC densitometric method for the simultaneous determination of MET, SAX, and DAP. Methods: Separation was performed using aluminum HPTLC sheets coated with silica gel 60 F254 with a mobile phase consisting of a mixture of acetonitrile: 1% w/v ammonium acetate in methanol (9: 1, v/v). Scanning was performed at 210 nm. Results and Discussion: Linearity of the method was assessed in the concentration range of 0.25-10 μg/band for SAX and DAP and 0.25-25 μg/band for MET. The method was fully validated as per the ICH guidelines. The proposed method provided error and deviation values of less than 2% assessing good accuracy and precision. Conclusion: The method was successfully applied to the analysis of pharmaceutical tablets of MET/SAX, MET/DAP, and SAX/DAP with high specificity.

Systemic sclerosis (SSc) is a multi-organ autoimmune disease with complex interactions between immune-mediated inflammatory processes and vascular pathology leading to small vessel obliteration, promoting uncontrolled fibrosis of skin and internal organs. Interstitial lung disease (ILD) is a common but highly variable manifestation of SSc and is associated with high morbidity and mortality. Treatment approaches have focused on immunosuppressive therapies, which have shown some efficacy on lung function. Recently, a large phase 3 trial showed that treatment with nintedanib was associated with a reduction in lung function decline. None of the conducted randomized clinical trials have so far shown convincing efficacy on other outcome measures including quality of life determined by patient reported outcomes. Little evidence is available for non-pharmacological treatment and supportive care specifically for SSc-ILD patients, including pulmonary rehabilitation, supplemental oxygen, symptom relief and adequate information. Improved management of SSc-ILD patients based on a holistic approach is necessary to support patients in maintaining as much quality of life as possible throughout the disease course and to improve long-term outcomes.

Objectives To assess the diagnostic accuracy of fast acquisition MRI in suspected cases of paediatric appendicitis presenting to a tertiary referral hospital. Materials and methods A prospective study was undertaken between May and October 2017 of 52 children who presented with suspected appendicitis and were referred for an abdominal ultrasound. All patients included in this study received both an abdominal ultrasound and five-sequence MRI consisting of axial and coronal gradient echo T2 scans, fat-saturated SSFSE and a diffusion-weighted scan. Participants were randomised into groups of MRI with breath-holds or MRI with free breathing. A patient satisfaction survey was also carried out. Histopathology findings, where available, were used as a gold standard for the purposes of data analysis. Statistical analysis was performed, and p values < 0.05 were considered statistically significant. Results Ultrasound had a sensitivity and specificity of 25% and 92.9%, respectively. MRI with breath-hold had a sensitivity and specificity of 81.8% and 66.7%, respectively, whilst MRI with free breathing was superior with sensitivity and specificity of 92.3% and 84.2%, respectively. MRI with free breathing was also more time efficient (p < 0.0001). Group statistics were comparable (p < 0.05). Conclusions The use of fast acquisition MRI protocols, particularly free breathing sequences, for patients admitted with suspected appendicitis can result in faster diagnosis, treatment and discharge. It also has a statistically significant diagnostic advantage over ultrasound. Additionally, the higher specificity of MR can reduce the number of negative appendectomies performed in tertiary centres.

Background: Patient centred healthcare is the corner stone to many healthcare strategies. Patient specific health needs should be at the fore of healthcare improvements and quality measurements. Patient reported outcome measures (PROM) that support real world clinical effectiveness assessments are increasingly being used to highlight domains where there is the greatest scope for change. Objectives: This systematic review aims to identify and evaluate existing patient reported assessment measures/tool(s) that can be used in developing a PROM for postpartum women. We will assess and evaluate their measurement properties in a transparent and structured way in accordance with the COSMIN guidelines. Methods: Methodological guidelines for systematic reviews of PROMs have been developed by the COSMIN initiative and will be followed for this systematic review. A systematic literature review will be performed using PubMed, CINAHL and EMBASE from inception to the present day. Two reviewers independently will judge eligibility, conduct data extraction and assess the methodological quality of each study as per COSMIN guidelines. Inclusion criteria: studies should concern PROM with an aim to evaluate measurement properties in the development or the evaluation of a PROM of interest. Included PROM will focus upon postpartum women assessing morbidity and quality of care. All peer reviewed studies with an assessment tool designed for patient completion will be considered. Exclusion criteria; abstract, letters and non-peer reviewed publications. Studies will be graded on measurement properties and quality of evidence as laid out by COSMIN. All studies and characteristics eligible for inclusion will be summarised and a recommendation to the most suitable measurement tool(s) will be given. Discussion: We will provide a comprehensive description of all available patient reported assessment tools available for childbirth and postpartum quality of life and recommend based on COSMIN guidelines the most suitable instrument(s) available for use.

Objective: Limited evidence exists on the role that the cause of chronic kidney disease plays in determining pregnancy outcomes. The aim of this systematic review and meta-analysis was to examine the association between chronic kidney disease and adverse pregnancy outcomes by the cause and severity of chronic kidney disease where reported. The protocol was registered under the International Prospective Register of Systematic Reviews (CRD42020211925). Data Sources: PubMed, Embase, and Web of Science were searched until May 24, 2021, supplemented with reference list checking. Study Eligibility Criteria: Studies that compared the pregnancy outcomes in women with or without chronic kidney disease were included. Two reviewers independently screened titles, abstracts, and full-text articles according to a priori defined inclusion criteria. Methods: Data extraction and quality appraisal were performed independently by 3 reviewers. The grading of recommendations, assessment, development, and evaluation approach was used to assess the overall certainty of the evidence. Random-effects meta-analyses were used to calculate the pooled estimates using the generic inverse variance method. The primary outcomes included preeclampsia, cesarean delivery, preterm birth (

PURPOSE OF REVIEW: Radiological imaging has a crucial role in pulmonary evaluation in cystic fibrosis (CF), having been shown to be more sensitive than pulmonary function testing at detecting structural lung changes. The present review summarizes the latest published information on established and evolving pulmonary imaging techniques for assessing people with this potentially life-limiting disorder. RECENT FINDINGS: Chest computed tomography (CT) has taken over the predominant role of chest radiography in many centres for the initial assessment and surveillance of CF lung disease. However, several emerging techniques offer a promising means of pulmonary imaging using less ionizing radiation. This is of particular importance given these patients tend to require repeated imaging throughout their lives from a young age. Such techniques include ultra-low-dose CT, tomosynthesis, dynamic radiography and magnetic resonance imaging. In addition, deep-learning algorithms are anticipated to improve diagnostic accuracy. SUMMARY: The recent introduction of triple-combination CF transmembrane regulator therapy has put further emphasis on the need for sensitive methods of monitoring treatment response to allow for early adaptation of treatment regimens in order to limit irreversible lung damage. Further research is needed to establish how emerging imaging techniques can contribute to this safely and effectively.

Objective Chronic kidney disease (CKD) has been linked with adverse pregnancy outcomes, but few studies have examined the influence of cause and severity. The aim of this meta-analysis was to synthesize the evidence on CKD and adverse pregnancy outcome, by cause and severity of CKD where reported. Data sources We searched PubMed, Embase, and Web of Science from inception to May 2021. Study selection and Data Extraction: Studies reporting associations between CKD and adverse pregnancy outcomes were included according to pre-defined eligibility criteria (PROSPERO protocol registration: CRD42020211925). Two reviewers independently screened titles, abstracts, and full-text articles and performed data extraction. The certainty of the evidence was assessed using the GRADE approach. Main Outcomes and Measures: We used random-effects meta-analyses to calculate pooled estimates. Primary outcomes included pre-eclampsia, Caesarean section (CS), preterm birth (PTB Results In total, 31 studies were included. The certainty of the evidence was deemed to be ‘very low' for all outcomes using the GRADE approach as expected given the observational study design. Pre-pregnancy CKD was associated with pre-eclampsia [pooled adjusted odds ratio (aOR)=2.58 (1.33-5.01)], CS [aOR=1.65 (1.21-2.25)], PTB [aOR=1.73 (1.31-2.27)] and SGA [aOR= 1.93 (1.06-3.52)]. Subgroup analyses suggested that different causes of CKD had differing risks for adverse pregnancy outcomes, and later stages of CKD, compared to earlier stages, were associated with higher odds of pre-eclampsia [crude OR = 2.77 (1.73-4.44)], PTB [4.21 (2.99-5.92)], and SGA [2.43 (1.33-4.46)]. Conclusions CKD was associated with a higher risk of adverse pregnancy outcomes, and the degree of risk varied by cause and severity. These findings highlight the need for further studies of a more robust quality evaluating the effects of cause and severity of kidney disease on adverse pregnancy outcomes. Key messages Pre-pregnancy CKD was associated with higher risk of adverse pregnancy outcomes. The risk of adverse pregnancy outcomes varied by CKD cause and severity.

Summary Background Systemic sclerosis-associated interstitial lung disease (ILD) carries a high mortality risk; expert guidance is required to aid early recognition and treatment. We aimed to develop the first expert consensus and define an algorithm for the identification and management of the condition through application of well established methods. Methods Evidence-based consensus statements for systemic sclerosis-associated ILD management were established for six domains (ie, risk factors, screening, diagnosis and severity assessment, treatment initiation and options, disease progression, and treatment escalation) using a modified Delphi process based on a systematic literature analysis. A panel of 27 Europe-based pulmonologists, rheumatologists, and internists with expertise in systemic sclerosis-associated ILD participated in three rounds of online surveys, a face-to-face discussion, and a WebEx meeting, followed by two supplemental Delphi rounds, to establish consensus and define a management algorithm. Consensus was considered achieved if at least 80% of panellists indicated agreement or disagreement. Findings Between July 1, 2018, and Aug 27, 2019, consensus agreement was reached for 52 primary statements and six supplemental statements across six domains of management, and an algorithm was defined for clinical practice use. The agreed statements most important for clinical use included: all patients with systemic sclerosis should be screened for systemic sclerosis-associated ILD using high-resolution CT; high-resolution CT is the primary tool for diagnosing ILD in systemic sclerosis; pulmonary function tests support screening and diagnosis; systemic sclerosis-associated ILD severity should be measured with more than one indicator; it is appropriate to treat all severe cases; no pharmacological treatment is an option for some patients; follow-up assessments enable identification of disease progression; progression pace, alongside disease severity, drives decisions to escalate treatment. Interpretation Through a robust modified Delphi process developed by a diverse panel of experts, the first evidence-based consensus statements were established on guidance for the identification and medical management of systemic sclerosis-associated ILD. Funding An unrestricted grant from Boehringer Ingelheim International.

Although several genetic associations with scleroderma (SSc) are defined, very little is known on genetic susceptibility to SSc-associated interstitial lung disease (SSc-ILD). A number of common polymorphisms have been associated with SSc-ILD, but most have not been replicated in separate populations. Four SNPs in IRF5, and one in each of STAT4, CD226 and IRAK1, selected as having been previously the most consistently associated with SSc-ILD, were genotyped in 612 SSc patients, of European descent, of whom 394 had ILD. The control population (n = 503) comprised individuals of European descent from the 1000 Genomes Project. After Bonferroni correction, two of the IRF5 SNPs, rs2004640 (OR (95% CI)1.30 (1.10–1.54), pcorr = 0.015) and rs10488631 (OR 1.48 (1.14–1.92), pcorr = 0.022), and the STAT4 SNP rs7574865 (OR 1.43 (1.18–1.73), pcorr = 0.0015) were significantly associated with SSc compared with controls. However, none of the SNPs were significantly different between patients with SSc-ILD and controls. Two SNPs in IRF5, rs10488631 (OR 1.72 (1.24–2.39), pcorr = 0.0098), and rs2004640 (OR 1.39 (1.11–1.75), pcorr = 0.03), showed a significant difference in allele frequency between controls and patients without ILD, as did STAT4 rs7574865 (OR 1.86 (1.45–2.38), pcorr = 6.6 × 10−6). A significant difference between SSc with and without ILD was only observed for STAT4 rs7574865, being less frequent in patients with ILD (OR 0.66 (0.51–0.85), pcorr = 0.0084). In conclusion, IRF5 rs2004640 and rs10488631, and STAT4 rs7574865 were significantly associated with SSc as a whole. Only STAT4 rs7574865 showed a significant difference in allele frequency in SSc-ILD, with the T allele being protective against ILD.Key points• We confirm the associations of the IRF5 SNPs rs2004640 and rs10488631, and the STAT4 SNP rs7574865, with SSc as a whole.• None of the tested SNPs were risk factors for SSc-ILD specifically.• The STAT4 rs7574865 T allele was protective against the development of lung fibrosis in SSc patients.• Further work is required to understand the genetic basis of lung fibrosis in association with scleroderma.

Rationale: Interstitial lung abnormalities (ILAs) are associated with the highest genetic risk locus for idiopathic pulmonary fibrosis (IPF); however, the extent to which there are unique associations among individuals with ILAs or additional overlap with IPF is not known. Objectives: To perform a genome-wide association study (GWAS) of ILAs. Methods: ILAs and a subpleural-predominant subtype were assessed on chest computed tomography (CT) scans in the AGES (Age Gene/Environment Susceptibility), COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease [COPD]), Framingham Heart, ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points), MESA (Multi-Ethnic Study of Atherosclerosis), and SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) studies. We performed a GWAS of ILAs in each cohort and combined the results using a meta-analysis. We assessed for overlapping associations in independent GWASs of IPF. Measurements and Main Results: Genome-wide genotyping data were available for 1,699 individuals with ILAs and 10,274 control subjects. The MUC5B (mucin 5B) promoter variant rs35705950 was significantly associated with both ILAs (P = 2.6 × 10(−27)) and subpleural ILAs (P = 1.6 × 10(−29)). We discovered novel genome-wide associations near IPO11 (rs6886640, P = 3.8 × 10(−8)) and FCF1P3 (rs73199442, P = 4.8 × 10(−8)) with ILAs, and near HTRE1 (rs7744971, P = 4.2 × 10(−8)) with subpleural-predominant ILAs. These novel associations were not associated with IPF. Among 12 previously reported IPF GWAS loci, five (DPP9, DSP, FAM13A, IVD, and MUC5B) were significantly associated (P

PurposeThe RGD-integrin, αvβ6, plays a role in the pathogenesis of pulmonary fibrosis through activation of transforming growth factor beta (TGFβ). This study sought to quantify expression of αvβ6 in the lungs of healthy humans and subjects with pulmonary fibrosis using the αvβ6-selective [18F]FB-A20FMDV2 PET ligand.Methods[18F]FB-A20FMDV2 PET/CT scans were performed in healthy subjects and those with fibrotic lung disease. Standard uptake values (SUV) and volume of distribution (VT) were used to quantify αvβ6 expression. In subjects with fibrotic lung disease, qualitative assessment of the relationship between αvβ6 expression and the distribution of fibrosis on high resolution computed tomography was conducted.ResultsA total of 15 participants (6 healthy, 7 with idiopathic pulmonary fibrosis (IPF) and 2 with connective tissue disease (CTD) associated PF) were enrolled.VTand SUV of [18F]FB-A20FMDV2 were increased in the lungs of subjects with pulmonary fibrosis (PF) compared with healthy subjects. Geometric meanVT(95% CI) was 0.88 (0.60, 1.29) mL/cm3for healthy subjects, and 1.40 (1.22, 1.61) mL/cm3for subjects with IPF; and SUV was 0.54 (0.36, 0.81) g/mL for healthy subjects and 1.03 (0.86, 1.22) g/mL for subjects with IPF. The IPF/healthyVTratio (geometric mean, (95% CI of ratio)) was 1.59 (1.09, 2.32) (probability ratio > 1 = 0.988)) and the SUV ratio was 1.91 (1.27, 2.87) (probability ratio > 1 = 0.996). Increased uptake of [18F]FB-A20FMDV2 in PF was predominantly confined to fibrotic areas. [18F]FB-A20FMDV2 measurements were reproducible at an interval of 2 weeks. [18F]FB-A20FMDV2 was safe and well tolerated.ConclusionsLung uptake of [18F]FB-A20FMDV2, a measure of expression of the integrin αvβ6, was markedly increased in subjects with PF compared with healthy subjects.

Aims The management of cranial chordomas is controversial. We provide a comprehensive review of the evolving patterns of care of cranial chordomas in the USA. Materials and methods We analysed the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2014 for clinical characteristics and long-term survival, and the National Surgical Quality Improvement Program (NSQIP) dataset between 2005 and 2016 for perioperative characteristics and surgical morbidity. Results In total, 936 patients were identified from the NCDB, 405 patients from SEER and 64 patients from the NSQIP. Most patients were men (56.2, 54.8 and 57.8% in NCDB, SEER and NSQIP, respectively) and White (80.9 and 83.2% in NCDB and SEER, respectively). Surgery was the preferred treatment modality (87.3% in NCDB and 86.2% in SEER). Surgery was carried out alone (41.8% in NCDB and 40.7% in SEER) or in combination with radiation (42.1% in NCDB and 45.4% in SEER). Proton therapy was the most common type of radiation (32.2% in NCDB), particularly after 2011. The median operative time, median hospital length and postoperative morbidity were significantly higher in chordoma patients compared with patients who underwent other skull-base procedures. The 5-year survival rate was 79.8% in NCDB and 76.9% in SEER. There was a trend towards longer survival in patients receiving surgery and radiation, which has been increasingly used since 2004. Patients younger than 60 years had a decreased risk of mortality. Conclusions Our analysis reflects patterns of care in the USA. The use of surgery and radiation is increasing, with a trend towards longer survival. Surgery is complicated with long operative time, hospital stay and a higher rate of complications.

Background Cervical cancer (CxCa) ranks as the fourth most prevalent women-related cancer worldwide. Therefore, there is a crucial need to develop newer treatment modalities. Ormeloxifene (ORM) is a non-steroidal, selective estrogen receptor modulator (SERM) that is used as an oral contraceptive in humans. Recent investigations suggest that ORM exhibits potent anti-cancer activity against various types of cancers. Nanoparticulates offer targeted delivery of anti-cancer drugs with minimal toxicity and promise newer approaches for cancer diagnosis and treatment. Therefore, the nanotherapy approach is superior compared to traditional chemotherapy, which is not site-specific and is often associated with various side effects. Methods Pursuing this novel nanotherapy approach, our lab has recently developed ORM-loaded poly [lactic-co-glycolic acid] (PLGA), an FDA-approved biodegradable polymer, nanoparticles to achieve targeted drug delivery and improved bioavailability. Our optimized PLGA-ORM nanoformulation showed improved internalization in both dose- and energy-dependent manners, through endocytosis-mediated pathways in both Caski and SiHa cell lines. Additionally, we employed MTS and colony forming assays to determine the short- and long-term effects of PLGA-ORM on these cells. Results Our results showed that this formulation demonstrated improved inhibition of cellular proliferation and clonogenic potential compared to free ORM. Furthermore, the PLGA-ORM nanoformulation exhibited superior anti-tumor activities in an orthotopic cervical cancer mouse model than free ORM. Conclusion Collectively, our findings suggest that our novel nanoformulation has great potential for repurposing the drug and becoming a novel modality for CxCa management.

Selective estrogen receptor modulator drug molecules of triphenylethylene family have gained considerable attention as anti-cancer agents. Despite recent advances in screening and development of HPV vaccines, cervical cancer remains one of the deadliest malignancies as advanced stage metastatic disease is mostly untreatable, thus warrants newer therapeutic strategies. Ormeloxifene (ORM) is a well-known SERM of triphenylethylene family that has been approved for human use, thus represents an ideal molecule for repurposing. In this study, we for the first time have demonstrated the anti-cancerous properties of ormeloxifene in cervical cancer. Ormeloxifene efficiently attenuated tumorigenic and metastatic properties of cervical cancer cells via arresting cell cycle at G1-S transition, inducing apoptosis, decreasing PI3K and Akt phosphorylation, mitochondrial membrane potential, and modulating G1-S transition related proteins (p21, cyclin E and Cdk2). Moreover, ORM repressed the expression of HPV E6/ E7 oncoproteins and restored the expression of their downstream target tumor suppressor proteins (p53, Rb and PTPN 13). As a result, ormeloxifene induces radio-sensitization in cervical cancer cells and caused potent tumor growth inhibition in orthotopic mouse model. Taken together, ormeloxifene represents an alternative therapeutic modality for cervical cancer which may have rapid clinical translation as it is already proven safe for human use.

A proportion of patients with interstitial lung diseases (ILDs), including the ILDs that are commonly associated with autoimmune diseases, develop a progressive fibrosing phenotype characterised by worsening of lung function, dyspnoea and quality of life, and early mortality. No drugs are approved for the treatment of ILDs other than idiopathic pulmonary fibrosis (IPF). At present, immunomodulatory medications are the mainstay of treatment for non-IPF ILDs. However, with the exception of systemic sclerosis-associated ILD, the evidence to suggest that immunosuppression may preserve lung function in patients with these ILDs comes only from retrospective, observational, or uncontrolled studies. In this article, we review the evidence for the treatments currently used to treat ILDs associated with autoimmune diseases and other ILDs and the ongoing trials of immunosuppressant and antifibrotic therapies in patients with these ILDs.Funding: Boehringer Ingelheim. ispartof: ADVANCES IN THERAPY vol:36 issue:7 pages:1518-1531 ispartof: location:United States status: published

Background: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a severe complication associated with a high mortality. However, evidence and guidance on management is sparse. The aim of this international survey was to assess differences in prevention, diagnostic and treatment strategies for AE-IPF in specialised and non-specialised ILD centres worldwide.Material and Methods: Pulmonologists working in specialised and non-specialised ILD centres were invited to participate in a survey designed by an international expert panel. Responses were evaluated in respect to the physicians' institutions.Results: Three hundred and two (65%) of the respondents worked in a specialised ILD centre, 134 (29%) in a non-specialised pulmonology centre. Similarities were frequent with regards to diagnostic methods including radiology and screening for infection, treatment with corticosteroids, use of high-flow oxygen and non-invasive ventilation in critical ill patients and palliative strategies. However, differences were significant in terms of the use of KL-6 and pathogen testing in urine, treatments with cyclosporine and recombinant thrombomodulin, extracorporeal membrane oxygenation in critical ill patients as well as antacid medication and anaesthesia measures as preventive methods.Conclusion: Despite the absence of recommendations, approaches to the prevention, diagnosis and treatment of AE-IPF are comparable in specialised and non-specialised ILD centres, yet certain differences in the managements of AE-IPF exist. Clinical trials and guidelines are needed to improve patient care and prognosis in AE-IPF.

The COVID-19 pandemic identified an urgent need to re-evaluate the provision of spirometry for clinical monitoring. Home spirometry offers the opportunity for real-time disease evaluation without risk of nosocomial infection. To determine the utility of home spirometry in interstitial lung disease (ILD), interim data from the ongoing INJUSTIS study was evaluated. High correlation was observed between home and hospital spirometry at baseline(r=0.89) and three-months(r=0.82). Over 90% of home spirometry values were within Bland-Altman agreement limits at both time points, although frequently underestimated hospital values. Home spirometry is feasible in people with fibrotic ILD.

Key Points Question Are underlying inflammatory pathways and body composition profiles associated with less favorable 5-year colon cancer outcomes? Findings In this cohort study including 28 patients with nonmetastatic colon cancer, high visceral fat and low muscle mass were associated with increased inflammatory activity and poor 5-year cancer outcomes, including recurrence and disease-specific mortality. Low skeletal muscle area and high visceral to total fat ratio were associated with increased expression of proinflammatory cytokines and vascular endothelial growth factor and inhibition of protective inhibitory cytokines in patients with less favorable 5-year cancer outcomes. Meaning These findings suggest that less favorable colon cancer outcomes associated with low skeletal muscle area and high visceral to total fat ratio were also associated with increased expression of proinflammatory cytokines and vascular endothelial growth factor and lower levels of protective inhibitory cytokines., This cohort study examines associations among body composition profiles, inflammatory marker expressions, and 5-year colon cancer outcomes., Importance Obesity, particularly visceral obesity and sarcopenia, are poor prognostic indicators in colon cancer. Objectives To explore the association between body composition profiles and 5-year colon cancer outcomes and delineate the associated underlying inflammatory processes. Design, Setting, and Participants This multicenter translational cohort study included patients with nonmetastatic colon cancer who did not have underlying chronic inflammatory disorders and were not receiving anti-inflammatory drugs referred to tertiary cancer centers from 2009 to 2015. Preoperative acute phase proteins (white cell count, C-reactive protein, and albumin), cytokines (interleukin [IL]-1b, IL-2, IL-6, IL-10, interferon γ, and tumor necrosis factor α), vascular endothelial growth factor (VEGF), and cell surface receptor expression levels (CD11b and CD14) were measured. All patients underwent follow-up for at least 5 years. Data were analyzed in December 2020. Exposure Nonmetastatic colon cancer. Main Outcomes and Measures The associations of body composition profiles with 5-year cancer recurrence and disease-specific mortality were analyzed using Mantel Cox log-rank test and Kaplan-Meier curves. Results A total of 28 patients were included (median [interquartile range] age, 67 [58-72] years; 22 [78.6%] men). Low skeletal muscle area (SMA) and high visceral to total fat ratio were associated with poor clinical and oncological outcomes, including increased 5-year recurrence (low SMA: hazard ratio [HR], 2.30 [95% CI, 1.41-2.89]; P = .04; high visceral to total fat ratio: HR, 5.78 [95% CI, 3.66-7.95]; P = .02). High visceral to total fat ratio was associated with increased 5-year disease-specific mortality (HR, 5.92 [95% CI, 4.04-8.00]; P = .02). Patients with low SMA who developed a cancer recurrence, compared with those who did not, had higher C-reactive protein (mean [SD], 31.24 [6.95] mg/dL vs 8.11 [0.58] mg/dL; P = .003), IL-6 (mean [SD], 1.93 [1.16] ng/mL vs 0.88 [0.14] ng/mL; P = .004), VEGF (mean [SD], 310.03 [122.66] ng/mL vs 176.12 [22.94] ng/mL; P = .007), and CD14 (mean [SD], 521.23 [302.02] ng/mL vs 322.07 [98.35] ng/mL; P = .03) expression and lower albumin (mean [SD], 3.8 [0.6] g/dL vs 43.50 [3.69] g/dL; P = .01), IL-2 (mean [SD], 0.45 [0.25] ng/mL vs 0.94 [0.43] ng/mL; P

BackgroundFibrotic interstitial lung disease (fILD) has previously been associated with the presence of autoantibody. While studies have focused on systemic autoimmunity, the role of local autoantibodies in the airway remains unknown. We therefore extensively characterised the airway and peripheral autoantibody profiles in patients with fILD and assessed association with disease severity and outcome.MethodsBronchoalveolar lavage (BAL) was collected from a cohort of fILD patients and total airway antibody concentrations were quantified. An autoantigen microarray was used to measure IgG and IgA autoantibodies against 124 autoantigens in BAL from 40 idiopathic pulmonary fibrosis (IPF), 20 chronic hypersensitivity pneumonitis (CHP), 20 connective tissue disease-associated ILD (CTD-ILD) patients and 20 controls.ResultsA subset of patients with fILD but not healthy controls had a local autoimmune signature in their airways that was not present systemically, regardless of disease. The proportion of patients with IPF with a local autoantibody signature was comparable to that of CTD-ILD, which has a known autoimmune pathology, identifying a potentially novel subset of patients. The presence of an airway autoimmune signature was not associated with reduced survival probability or changes in lung function in the cohort as a whole. Patients with IPF had increased airway total IgA and IgG1 while subjects with CHP had increased airway IgA, IgG1 and IgG4. In patients with CHP, increased airway total IgA was associated with reduced survival probability.ConclusionThe presence of airway autoantibodies identifies a unique subset of patients with fILD and the mechanisms by which these autoantibodies contribute to disease requires further investigation.