From Inception to Malignancy: the Co-evolution of Pancreatic Cancer and Its Immunosuppressive Microenvironment.

Published in Cancer Research in 2007, Clark and colleagues first introduced the concept that the immune microenvironment evolves in lockstep with the progression of pancreatic cancer. Leveraging genetically engineered mouse models of the disease that were described a few years earlier, Clark and colleagues used a combination of approaches to describe the dynamics of immune evolution in precursor lesions all the way to overt malignancy. They discovered that immunosuppression is established at the earliest stages of carcinogenesis. Here, we discuss their findings, how they led to a wealth of functional work, and how they have been expanded upon since the advent of -omics technologies. See related article by Clark and colleagues, Cancer Res 2007;67:9518-27.

A phase II study of tepotinib in patients with advanced solid cancers harboring MET exon 14 skipping mutations or amplification (KCSG AL19-17).

BACKGROUND: We evaluated the efficacy and safety of tepotinib in patients with various solid cancers harboring MET exon 14 skipping mutation (METex14) or MET gene amplification. PATIENTS AND METHODS: A phase II, multicenter study was conducted in patients with advanced or metastatic solid cancers who progressed after standard treatment, harboring either METex14 or MET amplification detected in tissue-based next-generation sequencing (NGS). The primary endpoint was objective response rate (ORR). For exploratory analyses, we analyzed the gene profiles using plasma NGS test. RESULTS: Thirty-five patients were enrolled. The ORR was 57.6% for all patients, 52.2% for those with METex14, and 70% for those with MET amplification. Median progression-free survival (PFS) was 8 months [95% confidence interval (CI) 4.5-11.5 months] and median overall survival (OS) was 14 months (95% CI 7.8-20.2 months) in all patients. For patients with non-small-cell lung cancer with METex14, the median PFS was 9 months (95% CI 4.7-13.4 months) and the median OS was 17 months [95% CI not applicable (NA)-NA]. For patients with MET amplification, the median PFS was 7 months (95% CI 1.5-12.5 months) and the median OS was 10 months (95% CI 5.8-14.2 months). The ORR of patients with MET dysregulation detected by plasma NGS was 72.2%, whereas the ORR was 30% in those without detection. The most common adverse events were peripheral edema, asthenia, transaminase elevation, and anorexia, mostly grade 1 or 2. CONCLUSIONS: Tepotinib demonstrated consistent antitumor activity in patients with METex14, and promising antitumor activity in various cancers with MET amplification. Detection of MET dysregulation by plasma NGS may predict the response to tepotinib.

The Pneumothorax And Symptom Evaluation (PASE) study: Bendopnoea in patients with pneumothorax.

Background: Pneumothorax can cause distressing breathlessness, however the effect of the accumulated air in the pleural space and its association with diaphragmatic function and symptoms of breathlessness is not well understood. Bendopnoea is an evolving clinical symptom that has been demonstrated as clinically useful in some heart and lung conditions. Whether bendopnoea is present in patients with pneumothorax, and its potential clinical usefulness has not yet been investigated. The PASE study is a pilot study to explore the incidence and clinical relevance of bendopnoea in patients with pneumothorax and may provide better understanding of pneumothorax related dyspnoea. Methods: PASE is a prospective study. Eligible patients are assessed at baseline (pre air drainage/lung reinflation) and in patients whose pneumothorax resolves once the lung has re-expanded (post conservative management or air drainage procedure). Outcome measures include the incidence of bendopnoea, correlation of the associated symptoms (pain and breathlessness) to the severity of bendopnoea and the size of pneumothorax; and correlation with clinical outcome (i.e., response to air drainage/lung reinflation). The study will recruit 50 participants. Discussion: This is the first study to explore bendopnoea in patients with pneumothorax. The presence and significance of bendopnoea in relation to clinical and physiological parameters in patients with pneumothorax requires investigation. The findings of this study may further current understanding of dyspnoea related pneumothorax. Trial Registration: Name of the registry: Australia New Zealand Clinical Trial Registry Trial registration number : ACTRN12623001109695p. URL of the trial registry record for this trial : https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=386631&isReview=true Date of registration : Registered on 24 October 2023. Funding of the trial : This study has not received grant support. The study is sponsored by the Institute for Respiratory Health, a not-for-profit organisation. Name and contact information for the trial sponsor : Mr Bi Lam; Finance manager. Level 2, 6 Verdun Street, Nedlands, WA 6009. Role of sponsor : The funder is not involved in the planning of the study, gathering, analysing, and interpreting the data, or in preparing the manuscript. Protocol version : 1.

An innovative model of delivering cancer care in the community: the experience of a tertiary cancer centre in Singapore.

BACKGROUND: Cancer care has evolved rapidly, increasing the demand on healthcare resources. While many non-oral cancer treatments are administered in the hospital, not all necessitate complex medical care. Treatments that can be administered subcutaneously, intramuscularly, or as short intravenous infusions with a low risk of extravasation can be safely administered in the community. PATIENTS AND METHODS: Since 2017, the National University Cancer Institute, Singapore (NCIS) has operated a program called NCIS on-the-go (NOTG) comprising a network of community cancer treatment clinics located within 20 km of the hospital. NOTG provides 17 low-risk treatments and nursing services run by oncology-trained nurses without on-site physicians. Patients who receive their first dose of cancer treatment uneventfully in the cancer centre can opt-in to receive subsequent doses at any NOTG clinic. RESULTS: Treatment at NOTG has become more mainstream over the years, with its workload increasing by over sevenfold since 2017, and is now responsible for ∼10% of the total main cancer centre workload. The program is sustainable and financially viable to operate. A survey of 155 patients revealed a 96.8% user satisfaction rate, with the majority reporting tangible savings in travelling time, waiting time, and travelling costs. The diversion of low-risk treatments to NOTG has indirectly increased capacity and reduced waiting times at the main cancer centre for patients requiring complex cancer treatments, resulting in a win-win situation. CONCLUSIONS: NOTG represents an innovative model of care to deliver low-risk cancer treatments safely in the community and can be easily replicated in other countries.

DUETS for Light's in separating exudate from transudate.

BACKGROUND: Fifty years since its inception, Light's criteria have aided in classifying pleural effusions (PEs) as exudates if 1 or more criteria are met. Thoracic ultrasound (US) emerges as a non-invasive technique for point of care use especially if pleural procedures are contemplated. OBJECTIVE: We aimed to develop a score based on radiological and US features that could separate exudates from transudates without serum and pleural fluid biochemical tests necessary for Light's criteria. METHODS: A prospective review of consecutive patients with PE who underwent thoracocentesis was performed. CXRs were evaluated for laterality followed by US for echogenicity, pleural nodularity, thickening and septations. PE was classified as exudate or transudate according to Light's criteria and corroborated with albumin gradient. A score combining radiological and US features was developed. RESULTS: We recruited 201 patients with PE requiring thoracocentesis. Mean age was 64 years, 51% were females, 164 (81.6%) were exudates, and 37 (18.4%) were transudates. Assigning 1-point for Diaphragmatic nodularity, Unilateral, Echogenicity, Pleural Thickening and Septations, DUETS ranged from 1 to 5. DUETS ≥2 indicated high likelihood for exudate (PPV 98.8%, NPV 100%) with 1% misclassification versus 6.9% using Light's criteria (p < 0.001). CONCLUSION: DUETS separated exudates from transudates with good accuracy, and could obviate paired serum and pleural fluid tests necessary for Light's criteria computation. Our study reflected real world practice where DUETS performed better than Light's criteria for PE that arose from more than one disease processes, and in the evaluation of patients with PE who have received diuretics.

The third PLeuralEffusion And Symptom Evaluation (PLEASE-3) study: Bendopnoea in patients with pleural effusion.

Background: Pleural effusions often cause disabling breathlessness, however the mechanism is unknown. Patients with pleural effusions are subjected to pleural fluid drainage on a 'trial and error' basis, as symptom relief varies. This population commonly complain of bendopnoea (breathlessness on bending forward) which has not been investigated. Our pilot data found bendopnoea was significantly associated with presence of pleural effusion. The PLEASE-3 study will evaluate bendopnoea as a screening test for effusion-related breathlessness, its predictive value of symptomatic benefits from fluid drainage and explore its underlying physiological mechanism. Methods: PLEASE-3 is a multi-centre prospective study. Eligible patients are assessed at baseline (pre-drainage) and for patients undergoing drainage, up to 72 h post-procedure. Outcome measures include the prevalence of bendopnoea, its correlation with size of effusion and its predictive value of breathlessness relief after drainage. The relationship of bendopnoea with breathlessness, physiological parameters, functional capacity and diaphragmatic characteristics will be assessed. The study will recruit 200 participants. Discussion: This is the first study to investigate bendopnoea in patients with pleural effusion. It has minimal exclusion criteria to ensure that the results are generalisable. The presence and clinical significance of bendopnoea in the context of pleural effusion requires thorough investigation. The post assessment of patients undergoing pleural fluid drainage will provide insight into whether the presence of bendopnoea is able to predict clinical outcomes. Trial Registration: Name of the registry: Australia New Zealand Clinical Trial Registry Trial registration number: ACTRN12622000465752. URL of the trial registry record for this trial: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=383639&isReview=true Date of registration: Registered on 24 March 2022. Funding of the trial: This study has received funding from the Sir Charles Gairdner Research Advisory Council research project grant. The study is sponsored by the Institute for Respiratory Health, a not-for-profit organisation. Name and contact information for the trial sponsor: Mr Bi Lam; Finance manager. Level 2, 6 Verdun Street, Nedlands WA 6009. t‖ + 61 8 6151 0877 e‖ bi.lam@resphealth.uwa.edu.au Role of sponsor : The funder is not involved in the planning of the study, gathering, analysing, and interpreting the data, or in preparing the manuscript.

Economic outcomes among microfinance group members receiving community-based chronic disease care: Cluster randomized trial evidence from Kenya.

BACKGROUND: Poverty can be a robust barrier to HIV care engagement. We assessed the extent to which delivering care for HIV, diabetes and hypertension within community-based microfinance groups increased savings and reduced loan defaults among microfinance members living with HIV. METHODS: We analyzed cluster randomized trial data ascertained during November 2020-May 2023 from 57 self-formed microfinance groups in western Kenya. Groups were randomized 1:1 to receive care for HIV and non-communicable diseases in the community during regular microfinance meetings (intervention) or at a health facility during routine appointments (standard care). Community and facility care provided clinical evaluations, medications, and point-of-care testing. The trial enrolled 900 microfinance members, with data collected quarterly for 18-months. We used a two-part model to estimate intervention effects on microfinance shares purchased, and a negative binomial regression model to estimate differences in loan default rates between trial arms. We estimated effects overall and by participant characteristics. RESULTS: Participants' median age and distance from a health facility was 52 years and 5.6 km, respectively, and 50% reported earning less than $50 per month. The probability of saving any amount (>$0) through purchasing microfinance shares was 2.7 percentage points higher among microfinance group members receiving community vs. facility care. Community care recipients and facility care patients saved $44.90 and $25.24 over 18-months, respectively, and the additional amount saved by community care recipients was statistically significant (p = 0.036). Overall and in stratified analyses, loan defaults rates were not statistically significantly different between community and facility care patients. CONCLUSIONS: Receiving integrated care in the community was significantly associated with modest increases in savings. We did not find any significant association between community-delivered care and reductions in loan defaults among HIV-positive microfinance group members. Longer follow up examination and formal mediation analyses are warranted.

Exploring patterns in mental health treatment and interests of single adults in the United States: a secondary data analysis.

Objective: The objective of this study is to examine mental health treatment utilization and interest among the large and growing demographic of single adults in the United States, who face unique societal stressors and pressures that may contribute to their heightened need for mental healthcare. Method: We analyzed data from 3,453 single adults, focusing on those with possible mental health treatment needs by excluding those with positive self-assessments. We assessed prevalence and sociodemographic correlates of mental health treatment, including psychotherapy and psychiatric medication use, and interest in attending psychotherapy among participants who had never attended. Results: 26% were in mental health treatment; 17% were attending psychotherapy, 16% were taking psychiatric medications, and 7% were doing both. Further, 64% had never attended psychotherapy, of which 35% expressed interest in future attendance. There were differences in current psychotherapy attendance and psychiatric medication use by gender and sexual orientation, with women and gay/lesbian individuals more likely to engage in both forms of mental health treatment. Additionally, interest in future psychotherapy among those who had never attended varied significantly by age, gender, and race. Younger individuals, women, and Black/African-American participants showed higher likelihoods of interest in psychotherapy. Conclusion: Our research highlights a critical gap in mental health treatment utilization among single adults who may be experiencing a need for those services. Despite a seemingly higher likelihood of engagement in mental health treatment compared to the general population, only a minority of single adults in our sample were utilizing mental health treatment. This underutilization and the observed demographic disparities in mental health treatment underscore the need for targeted outreach, personalized treatment plans, enhanced provider training, and policy advocacy to ensure equitable access to mental healthcare for single adults across sociodemographic backgrounds.

Joint ERS/EACTS/ESTS clinical practice guidelines on adults with spontaneous pneumothorax.

OBJECTIVES: The optimal management for spontaneous pneumothorax (SP) remains contentious, with various proposed approaches. This joint clinical practice guideline from the ERS, EACTS and ESTS societies provides evidence-based recommendations for the management of SP. METHODS: This multidisciplinary Task Force addressed 12 key clinical questions on the management of pneumothorax, using ERS methodology for guideline development. Systematic searches were performed in MEDLINE and Embase. Evidence was synthesised by conducting meta-analyses, if possible, or narratively. Certainty of evidence was rated with GRADE (Grading, Recommendation, Assessment, Development and Evaluation). The Evidence to Decision framework was used to decide on the direction and strength of the recommendations. RESULTS: The panel makes a conditional recommendation for conservative care of minimally symptomatic patients with primary spontaneous pneumothorax (PSP) who are clinically stable. We make a strong recommendation for needle aspiration over chest tube drain for initial PSP treatment. We make a conditional recommendation for ambulatory management for initial PSP treatment. We make a conditional recommendation for early surgical intervention for the initial treatment of PSP in patients who prioritise recurrence prevention. The panel makes a conditional recommendation for autologous blood patch in secondary SP patients with persistent air leak (PAL). The panel could not make recommendations for other interventions, including bronchial valves, suction, pleurodesis in addition to surgical resection or type of surgical pleurodesis. CONCLUSIONS: With this international guideline, the ERS, EACTS and ESTS societies provide clinical practice recommendations for SP management. We highlight evidence gaps for the management of PAL and recurrence prevention, with research recommendations made. SHAREABLE ABSTRACT: This update of an ERS Task Force statement from 2015 provides a concise comprehensive update of the literature base. 24 evidence-based recommendations were made for management of pneumothorax, balancing clinical priorities and patient views.https://bit.ly/3TKGp9e.

Association between long working hours and metabolic dysfunction-associated steatotic liver disease: a nationwide population-based study in Korea.

OBJECTIVES: Long working hour is a known risk factor for metabolic diseases. We explored the association between working hours and metabolic dysfunction-associated steatotic liver disease (MASLD). STUDY DESIGN: Data on working hours among 22,818 workers (11,999 females) from the Korea National Health and Nutrition Examination Survey (2013-2021) were used for this study. METHODS: MASLD was defined as a combination of hepatic steatosis combined with one or more of cardiometabolic risk factors (overweight/obesity, prediabetes/diabetes, raised blood pressure, hypertriglyceridemia, low high-density lipoprotein cholesterol). Hepatic steatosis was assessed using the hepatic steatosis index. Logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The overall prevalence of MASLD was 30.4% in men and 18.1% in women. Among male workers, 20.2% worked ≥55 h/week, whereas among female workers, 10.1% worked ≥55 h/week. Compared with working 35-40 h/week, working ≥55 h/week was positively associated with overweight/obesity (OR: 1.21; 95% CI: 1.05-1.40), pre-diabetes mellitus (pre-DM)/DM (OR: 1.20; 95% CI: 1.04-1.38), raised blood pressure (OR: 1.17; 95% CI: 1.02-1.35), and presence of any cardiometabolic risk factors (OR: 1.56; 95% CI: 1.21-2.02). The adjusted OR (95% CI) of the association between working hours and MASLD was 1.27 (1.09-1.47) for ≥55 h/week compared with working 35-40 h/week in male workers. In female workers, long working hours were not clearly associated with cardiometabolic risk factors and MASLD. CONCLUSION: Long working hours are positively associated with MASLD among Korean male workers. Policy interventions are needed to mitigate the adverse metabolic effects of prolonged working hours.

Joint ERS/EACTS/ESTS clinical practice guidelines on adults with spontaneous pneumothorax.

BACKGROUND: The optimal management for spontaneous pneumothorax (SP) remains contentious, with various proposed approaches. This joint clinical practice guideline from the ERS, EACTS and ESTS societies provides evidence-based recommendations for the management of SP. METHODS: This multidisciplinary Task Force addressed 12 key clinical questions on the management of pneumothorax, using ERS methodology for guideline development. Systematic searches were performed in MEDLINE and Embase. Evidence was synthesised by conducting meta-analyses, if possible, or narratively. Certainty of evidence was rated with GRADE (Grading of Recommendations, Assessment, Development and Evaluations). The Evidence to Decision framework was used to decide on the direction and strength of the recommendations. RESULTS: The panel makes a conditional recommendation for conservative care of minimally symptomatic patients with primary spontaneous pneumothorax (PSP) who are clinically stable. We make a strong recommendation for needle aspiration over chest tube drain for initial PSP treatment. We make a conditional recommendation for ambulatory management for initial PSP treatment. We make a conditional recommendation for early surgical intervention for the initial treatment of PSP in patients who prioritise recurrence prevention. The panel makes a conditional recommendation for autologous blood patch in secondary SP patients with persistent air leak (PAL). The panel could not make recommendations for other interventions, including bronchial valves, suction, pleurodesis in addition to surgical resection or type of surgical pleurodesis. CONCLUSIONS: With this international guideline, the ERS, EACTS and ESTS societies provide clinical practice recommendations for SP management. We highlight evidence gaps for the management of PAL and recurrence prevention, with research recommendations made.

Three-Dimensional Computed Tomography Image Reformation for Comparison of Foraminal Cross-Sectional Dimension in Patients Who Have Undergone Laminoplasty and Laminectomy with Fusion.

PURPOSE OF THE STUDY: Laminectomy with fusion (LF) is commonly performed with laminoplasty (LP) for cervical myelopathy. Foraminal stenosis is important in the surgical treatment of cervical myelopathy. LF and LP can affect foraminal size in different ways. This study aimed to compare foraminal dimensions after LF and LP using a medical computer-assisted design (CAD) program. MATERIAL AND METHODS: Computed tomography (CT) scans of the cervical vertebrae of 16 patients with cervical myelopathy were retrospectively viewed in the Digital Imaging and Communications in Medicine format on a CAD program. CT images were reformatted in an oblique plane perpendicular to the long axis of each foramen from C2-C3 to C6-C7. The narrowest foraminal crosssectional dimension (FCD) was measured and compared between the LF and LP groups at the operated, non-operated, and C4-C5 levels. The difference between the preoperative and postoperative FCDs was also calculated and compared between the operated and C4-C5 levels. Intra- and interobserver reliabilities for FCD measurements were evaluated using intraclass correlation coefficients. RESULTS AND DISCUSSION: At the operated spinal levels, the LF and LP groups showed decreased and increased mean FCDs, respectively. At the adjacent non-operated levels, the mean FCD slightly increased in both the groups. In the LF group, the difference between the preoperative and postoperative FCDs in the C4-C5 levels was larger than that in the other operated levels, but this difference was insignificant. CONCLUSIONS: LF and LP showed contrary results for FCD. Therefore, FCD and kyphosis should be considered for LF and LP. KEY WORDS: three-dimensional, foraminal cross-sectional dimension, laminoplasty, laminectomy fusion, computer-aided design, drafting system, preoperative-postoperative comparison.

Comparison of in-shoe plantar pressure between Korean combat boots and running shoes.

INTRODUCTION: Combat boots are special shoes designed for soldiers to wear during activities in rough terrain, such as long marches or military training. Combat boots have been known to cause high plantar pressure and increase the injury rate of the lower extremities. Therefore, this study aimed to compare the difference in in-shoe plantar pressure between Korean combat boots and running shoes. We hypothesised that the newest Korean combat boots would have comparable plantar pressure distribution with running shoes. METHODS: We prospectively recruited 30 asymptomatic male participants, who are candidates for military services, from the local area. Two types of shoes (the newly developed Korean combat boots and running shoes) were examined. Pedobarographic measurements were collected using the pedar-X in-shoe pressure measurement system. Peak pressure (PP), pressure time integral (PTI), contact area and contact time were analysed. RESULTS: Both PP and PTI at the region of central and lateral forefeet (FF) were significantly higher in combat boots. The contact area of combat boots was significantly lower at the region of the hallux, second-fifth toes, medial FF, central FF and midfoot. Contact time at the region of central FF and medial heel was significantly higher in combat boots. CONCLUSIONS: Understanding the plantar pressure distribution of combat boots can be helpful for developing combat boots and preventing injury. Based on the results of our study, the next-generation Korean combat boots should be developed to increase contact area and distribute impulse under the head of the metatarsal bone.

Low Temperature Dynamic Polaron Liquid in a Manganite Exhibiting Colossal Magnetoresistance.

Polarons-fermionic charge carriers bearing a strong companion lattice deformation-exhibit a natural tendency for self-localization due to the recursive interaction between electrons and the lattice. While polarons are ubiquitous in insulators, how they evolve in transitions to metallic and superconducting states in quantum materials remains an open question. Here, we use resonant inelastic x-ray scattering to track the electron-lattice coupling in the colossal magneto-resistive bi-layer manganite La_{1.2}Sr_{1.8}Mn_{2}O_{7} across its metal-to-insulator transition. The response in the insulating high-temperature state features harmonic emissions of a dispersionless oxygen phonon at small energy transfer. Upon cooling into the metallic state, we observe a drastic redistribution of spectral weight from the region of these harmonic emissions to a broad high energy continuum. In concert with theoretical calculations, we show that this evolution implies a shift in electron-lattice coupling from static to dynamic lattice distortions that leads to a distinct polaronic ground state in the low temperature metallic phase-a dynamic polaron liquid.

Leveraging the pleural space for anticancer therapies in pleural mesothelioma.

Most patients with pleural mesothelioma (PM) present with symptomatic pleural effusion. In some patients, PM is only detectable on the pleural surfaces, providing a strong rationale for intrapleural anticancer therapy. In modern prospective studies involving expert radiological staging and specialist multidisciplinary teams, the population incidence of stage I PM (an approximate surrogate of pleura-only PM) is higher than in historical retrospective series. In this Viewpoint, we advocate for the expansion of intrapleural trials to serve these patients, given the paucity of data supporting licensed systemic therapies in this setting and the uncertainties involved in surgical therapy. We begin by reviewing the unique anatomical and physiological features of the PM-bearing pleural space, before critically appraising the evidence for systemic therapies in stage I PM and previous intrapleural PM trials. We conclude with a summary of key challenges and potential solutions, including optimal trial designs, repurposing of indwelling pleural catheters, and new technologies.

Impact of the host immune response on the development of equine herpesvirus myeloencephalopathy in horses.

Herpesviruses establish a well-adapted balance with their host's immune system. Despite this co-evolutionary balance, infections can lead to severe disease including neurological disorders in their natural host. In horses, equine herpesvirus 1 (EHV-1) causes respiratory disease, abortions, neonatal foal death and myeloencephalopathy (EHM) in ~10 % of acute infections worldwide. Many aspects of EHM pathogenesis and protection from EHM are still poorly understood. However, it has been shown that the incidence of EHM increases to >70 % in female horses >20 years of age. In this study we used old mares as an experimental equine EHV-1 model of EHM to identify host-specific factors contributing to EHM. Following experimental infection with the neuropathogenic strain EHV-1 Ab4, old mares and yearling horses were studied for 21 days post-infection. Nasal viral shedding and cell-associated viremia were assessed by quantitative PCR. Cytokine/chemokine responses were evaluated in nasal secretions and cerebrospinal fluid (CSF) by Luminex assay and in whole blood by quantitative real-time PCR. EHV-1-specific IgG sub-isotype responses were measured by ELISA. All young horses developed respiratory disease and a bi-phasic fever post-infection, but only 1/9 horses exhibited ataxia. In contrast, respiratory disease was absent in old mares, but all old mares developed EHM that resulted in euthanasia in 6/9 old mares. Old mares also presented significantly decreased nasal viral shedding but higher viremia coinciding with a single fever peak at the onset of viremia. According to clinical disease manifestation, horses were sorted into an EHM group (nine old horses and one young horse) and a non-EHM group (eight young horses) for assessment of host immune responses. Non-EHM horses showed an early upregulation of IFN-α (nasal secretions), IRF7/IRF9, IL-1ß, CXCL10 and TBET (blood) in addition to an IFN-γ upregulation during viremia (blood). In contrast, IFN-α levels in nasal secretions of EHM horses were low and peak levels of IRF7, IRF9, CXCL10 and TGF-ß (blood) coincided with viremia. Moreover, EHM horses showed significantly higher IL-10 levels in nasal secretions, peripheral blood mononuclear cells and CSF and higher serum IgG3/5 antibody titres compared to non-EHM horses. These results suggest that protection from EHM depends on timely induction of type 1 IFN and upregulation cytokines and chemokines that are representative of cellular immunity. In contrast, induction of regulatory or TH-2 type immunity appeared to correlate with an increased risk for EHM. It is likely that future vaccine development for protection from EHM must target shifting this 'at-risk' immunophenotype.

Joint ERS/EACTS/ESTS clinical practice guidelines on adults with spontaneous pneumothorax

The optimal management for spontaneous pneumothorax (SP) remains contentious, with various proposed approaches. This joint clinical practice guideline from the ERS, EACTS and ESTS societies provides evidence-based recommendations for the management of SP. This multidisciplinary Task Force addressed 12 key clinical questions on the management of pneumothorax, using ERS methodology for guideline development. Systematic searches were performed in MEDLINE and Embase. Evidence was synthesised by conducting meta-analyses, if possible, or narratively. Certainty of evidence was rated with GRADE (Grading of Recommendations, Assessment, Development and Evaluations). The Evidence to Decision framework was used to decide on the direction and strength of the recommendations. The panel makes a conditional recommendation for conservative care of minimally symptomatic patients with primary spontaneous pneumothorax (PSP) who are clinically stable. We make a strong recommendation for needle aspiration over chest tube drain for initial PSP treatment. We make a conditional recommendation for ambulatory management for initial PSP treatment. We make a conditional recommendation for early surgical intervention for the initial treatment of PSP in patients who prioritise recurrence prevention. The panel makes a conditional recommendation for autologous blood patch in secondary SP patients with persistent air leak (PAL). The panel could not make recommendations for other interventions, including bronchial valves, suction, pleurodesis in addition to surgical resection or type of surgical pleurodesis. With this international guideline, the ERS, EACTS and ESTS societies provide clinical practice recommendations for SP management. We highlight evidence gaps for the management of PAL and recurrence prevention, with research recommendations made.