Assessing patient perception and preferences for outcomes in lung cancer resection surgery: a cross-sectional study.

Background: Surgical resection is the primary treatment for early-stage lung cancer, but little is known about the outcomes that truly matter to patients. This aim of our study was to identify the aspects of postoperative outcomes that matter most to patients undergoing lung cancer surgery and explore the influence of clinical and demographic factors on their importance ratings. Methods: We performed a cross-sectional study of patients undergoing lung resection for non-small cell lung cancer at our institution from November 2021 to May 2022. Patients were surveyed using a self-developed questionnaire and the European Organisation for Research and Treatment of Cancer core health-related quality of life questionnaire (EORTC QLQ-C30) prior to surgery. Ordinal logistic regression was performed to determine associations between individual patient factors and outcome importance ratings. Results: Forty patients completed the survey during the study period. Patients prioritized oncologic outcomes, with 95% rating R0 resection and cancer recurrence as "very important". Other important factors included overall survival (90%), postoperative complications (e.g., myocardial infarction: 92.5%, infection: 87.5%), and the need for reoperation (82.5%). Health-related quality of life factors, such as chronic pain (77.5%) and the ability to return to normal physical and exercise levels (75%), were also highly valued. Certain patient clinical and demographic factors demonstrated significant associations with importance placed on certain outcomes. Preoperative health-related quality of life scores did not influence outcome importance ratings. Conclusions: This study provides insights into the outcomes that matter most to patients undergoing lung cancer surgery. Oncologic outcomes and postoperative complications were prioritized, while scar-related factors were less important. Patient preferences varied based on demographic and clinical factors. Understanding these preferences can enhance shared decision-making and improve patient-centered care in thoracic surgical oncology.

Measuring activity-rest rhythms under different acclimation periods in a marine fish using automatic deep learning-based video tracking.

Most organisms synchronize to an approximately 24-hour (circadian) rhythm. This study introduces a novel deep learning-powered video tracking method to assess the stability, fragmentation, robustness and synchronization of activity rhythms in Xyrichtys novacula. Experimental X. novacula were distributed into three groups and monitored for synchronization to a 14/10 hours of light/dark to assess acclimation to laboratory conditions. Group GP7 acclimated for 1 week and was tested from days 7 to 14, GP14 acclimated for 14 days and was tested from days 14 to 21 and GP21 acclimated for 21 days and was tested from days 21 to 28. Telemetry data from individuals in the wild depicted their natural behavior. Wild fish displayed a robust and minimally fragmented rhythm, entrained to the natural photoperiod. Under laboratory conditions, differences in activity levels were observed between light and dark phases. However, no differences were observed in activity rhythm metrics among laboratory groups related to acclimation period. Notably, longer acclimation (GP14 and GP21) led to a larger proportion of individuals displaying rhythm synchronization with the imposed photoperiod. Our work introduces a novel approach for monitoring biological rhythms in laboratory conditions, employing a specifically engineered video tracking system based on deep learning, adaptable for other species.

Evaluation of different screening tools for detection of malnutrition in hospitalised patients.

AIMS AND OBJECTIVES: To assess the prevalence of malnutrition in hospitalised adult patients, and to evaluate the accuracy of the most commonly used nutritional screening tools for identifying individuals at risk of malnutrition. METHODS: A prospective cross-sectional study was conducted on a total of 248 hospitalised patients in internal medicine wards (mean age: 75.2 years; 39.5% females). Nutritional screening was performed within 48 h of admission using the following tools: Malnutrition Universal Screening Tool (MUST), Nutrition Risk Screening Tool (NRS-2002), Malnutrition Screening Tool (MST), Short Nutritional Assessment Questionnaire (SNAQ), and Mini Nutritional Assessment Short Form (MNA-SF). The criteria of the European Society for Clinical Nutrition and Metabolism (ESPEN) were used as the gold standard for defining malnutrition. Patients were also evaluated using the Subjective Global Assessment (SGA) and the Global Leadership Initiative on Malnutrition (GLIM) criteria. Accuracy was determined by examining sensitivity, specificity, and positive and negative predictive values, and diagnostic agreement was determined by calculation of Cohen's kappa (κ). The study is reported as per the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. RESULTS: The ESPEN criteria classified 20.2% of the hospitalised patients as malnourished. Overall, the MUST had the highest sensitivity (80.0%), specificity (74.7%) and positive predictive value (44.4%). For the subgroup of patients aged >65 years, the MNA-SF had high sensitivity (94.4%) but low specificity (39.0%). Based on Cohen's κ, the SGA and GLIM criteria showed low agreement with the ESPEN criteria. CONCLUSION: The MUST was the most accurate nutritional screening tool, through the MST is more easily applied in many clinical settings. A comprehensive assessment of malnutrition that considers muscle mass is crucial for the reliable diagnosis of malnutrition. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: The present findings underscore the importance of accurate assessment of the malnutrition status of hospitalised patients and the need for a reliable screening tool. No patient or public contribution.

Pulmonary thrombosis associated with COVID-19 pneumonia: Beyond classical pulmonary thromboembolism.

BACKGROUND: Classical pulmonary thromboembolism (TE) and local pulmonary thrombosis (PT) have been suggested as mechanisms of thrombosis in COVID-19. However, robust evidence is still lacking because this was mainly based on retrospective studies, in which patients were included when TE was suspected. METHODS: All patients with COVID-19 pneumonia underwent computed tomography and pulmonary angiography in a prospective study. The main objective was to determine the number and percentage of thrombi surrounded by lung opacification (TSO) in each patient, as well as their relationship with percentage of lung involvement (TLI), to distinguish classical TE (with a random location of thrombi that should correspond to a percentage of TSO equivalent to the TLI) from PT. We determined TLI by artificial intelligence. Analyses at patient level (TLI and percentage of TSO) and at thrombi level (TLI and TSO) were performed. RESULTS: We diagnosed TE in 70 out of 184 patients. Three (2-8) thrombi/patient were detected. The percentage of TSO was 100% (75-100) per patient, and TLI was 19.9% (4.6-35.2). Sixty-five patients (92.9%) were above the random scenario with higher percentage of TSO than TLI. Most thrombi were TSO (n = 299, 75.1%). When evaluating by TLI (<10%, 10%-20%, 20%-30% and >30%), percentage of TSO was higher in most groups. Thrombi were mainly in subsegmental/segmental arteries, and percentage of TSO was higher in all locations. CONCLUSIONS: Thrombi in COVID-19 were found within lung opacities in a higher percentage than lung involvement, regardless of TLI and clot location, supporting the hypothesis of local PT rather than "classic TE".

Improving Thoracic Surgery Ward Round Quality and Enhancing Patient Safety in a Referral Centre.

Introduction Ward rounds are vital clinical processes that facilitate an opportunity for daily review and management of thoracic surgery inpatients. The aim of this study was to compare thoracic surgery ward round documentation against locally agreed standards and design a template to improve the detail and uniformity of this process to enhance patient care. Materials and methods Data for this audit was collected retrospectively and prospectively. Data was collected during three auditing periods and managed on Microsoft Excel. Descriptive statistics were used for its analysis. Chi-square and Fisher's Exact tests were used to test for differences in reporting rates. Results and discussion Initially, a total of 199 ward round notes were reviewed. Imaging results (19%) and discharge planning (23%) were not reported. eCARE (electronic Clinical Assessment for Round Evaluation) was developed to ensure that all aspects of patient evaluation recommended by the guidelines were included. Reporting rates significantly improved after such changes. We analysed the effect of the new ward round note on discharge planning (23.3 vs 41%, p<0.001), complication rates (32.6 vs 21.9%, p=0.03), post-surgical length of stay (LOS) (7.0 vs 5.0, p<0.001). Conclusion Over a year, we audited the Thoracic Surgery Department's ward round documentation against locally agreed standards in line with national recommendations. Several important items were not regularly reported. Using closed-ended questions improved reporting rates, and patient care was optimised. Further research should explore the impact of this new documentation method on patient care and postoperative outcomes in our Trust as well as other cardiothoracic centres.

Outcomes of chest drain management using only air leak (without fluid) criteria for removal after general thoracic surgery-a drainology study.

Background: Chest drain management is a variable aspect of postoperative care in thoracic surgery, with different opinion for air and drain volume output. We aim to study if acceptable safety was maintained using air leak criteria alone. Methods: A 9-year retrospective analysis of protocolised chest drain management using digital drain air leak cut off less than 20 mL/min for more than 6 h for drain removal in patients undergoing general thoracic surgery. We excluded patients if a chest drain was not required nor removed during admission or if patients underwent volume reduction or pneumonectomy. Withdrawal criteria were suspected bleeding or chylothorax. Postoperative films were reviewed to document post-drain removal pneumothorax, pleural effusion, and reintervention (drain re-insertion). Results: Between 2012 and 2021, 1,187 patients had thoracic surgery under a single surgeon. Following exclusion and withdrawal criteria, 797 patients were left for analysis. The mean age [standard deviation (SD)] was 61 [16] years and 383 (48%) were male. Median [interquartile range (IQR)] duration of drain insertion was 1 [1-2] day with a median length of hospital stay of 4 [2-6] days. Post-drain removal pneumothorax was observed in 141 (17.7%), post-drain removal pleural effusion was observed in 75 (9.4%) and re-intervention (reinsertion of chest drain) required in 17 (2.1%). Conclusions: Our results demonstrate acceptable levels of safety using digital assessment of air leak as the sole criteria for drain removal in selected patients after general thoracic surgery.

Disparate behavioral types in wild and reared juveniles of gilthead seabream.

Fish differ consistently in behavior within the same species and population, reflecting distinct behavioral types (BTs). Comparing the behavior of wild and reared individuals provides an excellent opportunity to delve into the ecological and evolutionary consequences of BTs. In this work, we evaluated the behavioral variation of wild and reared juvenile gilthead seabreams, Sparus aurata, a highly relevant species for aquaculture and fisheries. We quantified behavioral variation along the five major axes of fish behavioral traits (exploration-avoidance, aggressiveness, sociability, shyness-boldness, and activity) using standardized behavioral tests and a deep learning tracking algorithm for behavioral annotation. Results revealed significant repeatability in all five behavior traits, suggesting high consistency of individual behavioral variation across the different axes in this species. We found reared fish to be more aggressive, social and active compared to their wild conspecifics. Reared individuals also presented less variance in their aggressiveness, lacking very aggressive and very tame individuals. Phenotypic correlation decomposition between behavioral types revealed two different behavioral syndromes: exploration-sociability and exploration-activity. Our work establishes the first baseline of repeatability scores in wild and reared gilthead seabreams, providing novel insight into the behavior of this important commercial species with implications for fisheries and aquaculture.

Food determines ephemerous and non-stable gut microbiome communities in juvenile wild and farmed Mediterranean fish.

Novel insights were provided by contrasting the composition of wild and farmed fish gut microbiomes because the latter had essentially different environmental conditions from those in the wild. This was reflected in the gut microbiome of the wild Sparus aurata and Xyrichtys novacula studied here, which showed highly diverse microbial community structures, dominated by Proteobacteria, mostly related to an aerobic or microaerophilic metabolism, but with some common shared major species, such as Ralstonia sp. On the other hand, farmed non-fasted S. aurata individuals had a microbial structure that mirrored the microbial composition of their food source, which was most likely anaerobic, since several members of the genus Lactobacillus, probably revived from the feed and enriched in the gut, dominated the communities. The most striking observation was that after a short fasting period (86 h), farmed gilthead seabream almost lost their whole gut microbiome, and the resident community associated with the mucosa had a very much reduced diversity that was highly dominated by a single potentially aerobic species Micrococcus sp., closely related to M. flavus. The results pointed to the fact that, at least for the juvenile S. aurata studied, most of the microbes in the gut were transient and highly dependent on the feed source, and that only after fasting for at least 2 days could the resident microbiome in the intestinal mucosa be determined. Since an important role of this transient microbiome in relation to fish metabolism could not be discarded, the methodological approach needs to be well designed in order not to bias the results. The results have important implications for fish gut studies that could explain the diversity and occasional contradictory results published in relation to the stability of marine fish gut microbiomes, and might provide important information for feed formulation in the aquaculture industry.

Determining the optimal time to report mortality after lobectomy for lung cancer: An analysis of the time-varying risk of death.

Objective: Surgical mortality has traditionally been assessed at arbitrary intervals out to 1 year, without an agreed optimum time point. The aim of our study was to investigate the time-varying risk of death after lobectomy to determine the optimum period to evaluate surgical mortality rate after lobectomy for lung cancer. Methods: We performed a retrospective study of patients undergoing lobectomy for lung cancer at our institution from 2015 to 2022. Parametric survival models were assessed and compared with a nonparametric kernel estimate. The hazard function was plotted over time according to the best-fit statistical distribution. The time points at which instantaneous hazard rate peaked and stabilized in the 1-year period after surgery were then determined. Results: During the study period, 2284 patients underwent lobectomy for lung cancer. Cumulative mortality at 30, 90, and 180 days was 1.3%, 2.9%, and 4.9%, respectively. Log-logistic distribution showed the best fit compared with other statistical distribution, indicated by the lowest Akaike information criteria value. The instantaneous hazard rate was greatest during the immediate postoperative period (0.129; 95% confidence interval, 0.087-0.183) and diminishes rapidly within the first 30 days after surgery. Instantaneous hazard rate continued to decrease past 90 days and stabilized only at approximately 180 days. Conclusions: In-hospital mortality is the optimal follow-up period that captures the early-phase hazard during the immediate postoperative period after lobectomy. Thirty-day mortality is not synonymous to "early mortality," as instantaneous hazard rate remains elevated well past the 90-day time point and only stabilizes at approximately 180 days after lobectomy.

Are chest drains routinely required after thoracic surgery? A drainology study of on-table chest-drain removals.

Objectives: Advances in perioperative management for thoracic surgery have accelerated the postoperative recovery of patients by decreasing postoperative pain and the incidence of complications. We aimed to study whether it's safe to remove chest drains on table in selected cases. Methods: This was a 5-year retrospective analysis of protocolized chest-drain removal on the operating table. The chest drain was removed in patients undergoing sublobar/wedge lung resection and other minor thoracic procedure (pleural biopsy, mediastinal mass biopsy/resection) via a thoracoscopic approach (video-assisted thoracoscopic surgery). Chest drains were removed at the end of the operation if air leak as documented by the digital drain was less than 20 mL/min. Outcome data on postdrain removal pneumothorax, effusion, and need for further intervention were obtained by reviewing the postoperative chest films, all reported by a radiologist. Results: Between 2016 and 2021, 107 patients underwent drain removal in theater. Mean age (standard deviation) was 58 (17) years and 54 (50.5%) were male. Postdrain removal pneumothorax occurred in 22 patients (21%), pleural effusion in 6 (5.6%), and 21 of 22 postoperative pneumothoraces were managed conservatively without reinsertion of chest drain. As it is our standard policy to leave no pneumothorax in patients undergoing surgical management of primary spontaneous pneumothorax, only 1 such patient (0.9%) had a drain reinserted as a result. The median (interquartile) length of hospital stay was 1 day (1-2), and 14 patients (13%) were discharged on surgery day. Conclusions: Our results demonstrate that on table chest-drain removal in selected cases is safe and repeatable using a digital drain, challenging the practice of routine drain insertion after thoracic surgery.

The effects of ischaemic conditioning on lung ischaemia-reperfusion injury.

Ischaemia-reperfusion injury (IRI) encompasses the deleterious effects on cellular function and survival that result from the restoration of organ perfusion. Despite their unique tolerance to ischaemia and hypoxia, afforded by their dual (pulmonary and bronchial) circulation as well as direct oxygen diffusion from the airways, lungs are particularly susceptible to IRI (LIRI). LIRI may be observed in a variety of clinical settings, including lung transplantation, lung resections, cardiopulmonary bypass during cardiac surgery, aortic cross-clamping for abdominal aortic aneurysm repair, as well as tourniquet application for orthopaedic operations. It is a diagnosis of exclusion, manifesting clinically as acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Ischaemic conditioning (IC) signifies the original paradigm of treating IRI. It entails the application of short, non-lethal ischemia and reperfusion manoeuvres to an organ, tissue, or arterial territory, which activates mechanisms that reduce IRI. Interestingly, there is accumulating experimental and preliminary clinical evidence that IC may ameliorate LIRI in various pathophysiological contexts. Considering the detrimental effects of LIRI, ranging from ALI following lung resections to primary graft dysfunction (PGD) after lung transplantation, the association of these entities with adverse outcomes, as well as the paucity of protective or therapeutic interventions, IC holds promise as a safe and effective strategy to protect the lung. This article aims to provide a narrative review of the existing experimental and clinical evidence regarding the effects of IC on LIRI and prompt further investigation to refine its clinical application.

Impact of society and national guidelines on patient selection for lung cancer surgery in the United Kingdom.

OBJECTIVES: We sought to evaluate the impact of different national clinical guidelines (with consistent and conflicting recommendations) on clinician's practice in the UK. METHODS: In this cohort study, we analysed data from National Lung Cancer Audit comprising all patients diagnosed with lung cancer between 2008 and 2013 within England and Wales for consistent (British Thoracic Society and National Institute of Clinical Excellence) recommendations for lower/more permissive lung function but opposing stage (N2) selection parameters for surgery. RESULTS: From 2008 to 2013, data from 167 192 patients with primary lung cancers were included. The proportion of patients undergoing surgery for lung cancer increased from 9.5% to 20.5% in 2013 (P < 0.001) as the number of general thoracic surgeons in the UK increased from 40 to 81 in the corresponding timeframe. Mean forced expiratory volume in 1 s of surgical patients increased from 76% (22) to 81% (22) in 2013 (P < 0.001). Of the patients undergoing surgery, the proportion of patients with N2 disease across the 6-year interval was broadly consistent between 8% and 11% without any evidence of trend (P = 0.125). CONCLUSIONS: Within 3 years of new clinical guideline recommendations, we did not observe any overall change suggesting greater selection for surgery on lower levels of lung function. When presented with conflicting recommendation, no observable change in selection was noted on surgery for N2 disease. The observed increase in surgical resection rates is more likely due to greater access to surgery (by increasing number of surgeons) rather than any impact of guideline recommendations.

National evaluation of risk factors for unplanned readmission after lung resection.

OBJECTIVES: Unplanned readmission is defined as the return to inpatient hospitalization within 30 days after discharge. Worldwide, its incidence after lung resection ranges between 8% and 50%, and it has been shown to impact both patient recovery and healthcare resources. Our goal was to identify the risk factors to prioritize early follow-ups. METHODS: We analysed data from the database of the Grupo Español de Cirugía Torácica Video-Asistida from 33 thoracic surgery departments over 15 months. Standard tests were used to compare the different risk groups. Our goal was to present the most relevant explanatory variables for readmission. RESULTS: A total of 174 of 2808 patients (6%) underwent unplanned readmission after a lobectomy. Of all the preoperative individual characteristics, only lung function was found to be a risk factor for readmission [forced expiratory volume in 1 s < 80%, risk ratio (RR) 1.78, P < 0.001; diffusing capacity of carbon monoxide <60%, RR 1.6, P = 0.02; and VO2 < 20 ml/kg/min, RR 1.59, P = 0.02]. The tumour's characteristics and the stage of the disease did not have an influence on the readmission rates. In the readmitted cohort, an open approach or thoracotomy was associated with more frequent readmissions (RR 1.77; P < 0.001). Strong adhesions (RR 1.81; P < 0.001) or adhesions occupying more than half of the hemithorax (RR 1.73, P < 0.001) were also found to be risk factors for readmission and for longer operative times. A length of stay of >10 days after a lobectomy was found to be a risk factor for readmission (RR 1.9). CONCLUSIONS: We identified preoperative, intraoperative and postoperative risk factors for readmission. This information can be a useful tool to help with the prioritization of early follow-ups, especially in centres with high workloads.

How to optimize your set-up for a VATS right upper lobectomy.

A 77-year-old woman with multiple ground-glass opacities, the largest of which measured 21 mm, has a biopsy-proven primary lung adenocarcinoma in her right upper lobe. We performed a 3-port right-sided VATS using the Copenhagen approach. There was no pleural effusion or evidence of pleural metastatic spread. A tumor was identified in the upper lobe. The surrounding lung tissue appeared normal.  We performed a multilevel intercostal block using 0.25% levobupivacaine. The inferior pulmonary ligament was divided. The superior pulmonary vein and 2 branches of the pulmonary artery to the right upper lobe were dissected, encircled, and divided using tan reloads of the Endo GIA stapler. The right upper lobe bronchus was dissected, encircled, and divided in a similar fashion using a purple reload of the Endo GIA stapler following a successful test inflation of the lower and middle lobes. The horizontal fissure was completed with further firings of the stapler. Lymph nodes from stations 2, 4, 7, 8, 9, 10, and 11 were sampled and sent separately for histological analysis. There was no parenchymal or stump leak to 20 cm H20 on the test inflation. Hemostasis and pneumostasis were checked and ensured. A single 24 Fr drain was placed in the apex. Hemostasis was complete. The incision was closed in layers.

The Impact of the SARS-CoV-2 Pandemic on the Emergency Department and Management of the Pediatric Asthmatic Patient.

INTRODUCTION: Asthma exacerbation is among the commonest causes for pediatric emergency room visits, and respiratory viruses are frequent triggers of such exacerbations. Few studies have evaluated the consequences of the novel human coronavirus that causes the illness currently known as COVID-19, in the pediatric population. PURPOSE: The objective of this study was to analyze the impact of the COVID-19 pandemic and lockdown measures on the emergency department in the pediatric asthmatic patient. PATIENTS AND METHODS: This retrospective observational study evaluated pediatric patients treated at the Pediatric Emergency Service for wheezing episodes. Changes in the number and characteristics of these patients over the same period of 2019 as compared to 2020 during the month following the alarm declaration (March 14 to April 15) were evaluated. RESULTS: In total, data of 30 asthma patients managed in the period after the declaration of the coronavirus pandemic and of 158 asthma patients managed in the pre-COVID-19 period were included. In 2020, patient visits decreased by 82% in 2019. No statistically significant differences among age, sex, oxygen saturation, fever status, or number of severe bronchospasm episodes were found. Nebulized medication usage was reduced significantly since the alarm declaration. No significant increase in requests for complementary testing in the COVID-19 period was found. No patient requiring hospital admission was found to be PCR SARS-CoV-2 positive. Median time spent in the emergency department decreased from 180 minutes in 2019 to 85 minutes in the COVID-19 era. CONCLUSION: The COVID-19 pandemic and ensuing lockdown measures have led to an extraordinary reduction in emergency visits to the pediatric service. The ongoing pandemic has also led to improvements in the approach to asthma exacerbations and wheezing, to reduce the risk of exposure to the virus, such as increased use of pressurized metered dose inhaler and decreased time in the Emergency Department.

MicroRNAs 142-3p, miR-155 and miR-203 Are Deregulated in Gastric MALT Lymphomas Compared to Chronic Gastritis.

BACKGROUND: Over the last years, our knowledge on pathogenesis of gastric MALT lymphoma has greatly improved, but its morphological diagnosis is still hampered by overlapping histological features with advanced chronic gastritis. MicroRNAs are deregulated in lymphomas, but their role and usefulness in gastric MALT lymphoma has not been extensively investigated. MATERIALS AND METHODS: We analyzed the expression of 384 miRNAs using TaqMan microRNA assay in a training series of 10 gastric MALT lymphomas, 3 chronic gastritis and 2 reactive lymph nodes. Then, significantly deregulated miRNAs were individually assessed by real-time PCR in a validation series of 16 gastric MALT lymphomas and 12 chronic gastritis. RESULTS: Gastric MALT lymphoma is characterized by a specific miRNA expression profile. Among the differentially expressed miRNAs, a significant overexpression of miR-142-3p and miR-155 and down-regulation of miR-203 was observed in gastric MALT lymphoma when compared to chronic gastritis. CONCLUSION: miR-142-3p, miR-155 and miR-203 expression levels might be helpful biomarkers for the differential diagnosis between gastric MALT lymphomas and chronic gastritis.

Hematopoiesis-related microRNA expression in myelodysplastic syndromes.

MicroRNAs (miRNAs) are negative regulators of expression of genes involved in hematopoiesis. The present study sought to link hematopoiesis-relevant miRNAs with myelodysplastic syndromes (MDS) and MDS progression to acute myeloid leukemia (AML). We assessed 25 mature miRNAs in total RNA from bone marrow (BM) and peripheral blood (PB) of 25 newly diagnosed patients with MDS and 12 controls. Twelve miRNAs in BM and six in PB were differentially expressed between patients with MDS and controls. Three of these miRNAs, belonging to the cluster 17-92, were overexpressed in both BM and PB. miR-15a in BM ( p = 0.034) and miR-16 in PB ( p = 0.005) were differentially expressed between low-risk and high-risk groups. miR-222 ( p = 0.0023) and miR-181a ( p = 0.014) expression was higher in AML than in MDS in both BM and PB. This study adds further evidence to the role of miRNAs in the pathogenesis of MDS and their transformation into AML.

Regulation of JAK2 by miR-135a: prognostic impact in classic Hodgkin lymphoma.

The behavior of classic Hodgkin lymphoma (cHL) is determined by both the intrinsic features of the tumor cells and the characteristics of the microenvironment, making the analysis of entire lymph nodes an effective approach to understanding the disease. We examined the influence of our previously reported 25-microRNA signature for cHL on clinical outcome in 89 homogeneously treated cHL patients with a median follow-up of 80 months. Patients with low miR-135a expression had a higher probability of relapse (P = .04) and a shorter disease-free survival (P = .02). Functional analysis of cHL cell lines showed that mature miR-135a levels increased after pre-miR-135a transfection, causing apoptosis and decreased cell growth. Target analysis showed a direct regulation by miR-135a of JAK2, a cytoplasmic tyrosine kinase involved in a specific subset of cytokine receptor signaling pathways. miR-135a-mediated JAK2 down-regulation led to decreased mRNA and protein levels of the antiapoptotic gene Bcl-xL, suggesting a role for Bcl-xL in miR-135a/JAK2-mediated apoptosis. Our findings confirm the critical role of miR-135a in the survival of cHL cells and in the prognosis of cHL patients, indicating that novel treatment approaches targeting miR-135a may potentially benefit these patients.

Common variants in NLRP2 and NLRP3 genes are strong prognostic factors for the outcome of HLA-identical sibling allogeneic stem cell transplantation.

The inflammasomes are macromolecular cytosolic complexes involved in the production of interleukin-1beta (IL-1beta) and IL-18 in response to several pathogen-derived stimuli. Such interleukins have been implicated in the origin of severe allogeneic stem cell transplant (allo-SCT) complications. We analyzed the relationship between the interindividual variability in inflammasome protein-encoding genes in donors and patients and clinical outcome after allo-SCT. Fourteen common genetic variants in 5 genes of the inflammasome, namely, NLRP1, NLRP2, NLRP3, CARD8, and CASP5, were genotyped in 133 human leukocyte antigen-identical sibling pairs undergoing allo-SCT. In the multivariate analysis, donor variants in NLRP2 and NLRP3 were the most important prognostic factors for the clinical outcome after allo-SCT. Thus, donor TT genotype at rs10925027 in NLRP3 was associated with disease relapse (odds ratio (OR) = 6.3, P = 1 x 10(-7)), and donor GG genotype at rs1043684 in NLRP2 was associated with nonrelapse mortality (OR = 4.4, P = 6 x 10(-4)) and overall survival (OR = 3.1, P = .001). In addition, patient AA genotype at rs5862 in NLRP1 was associated with nonrelapse mortality (OR = 2.8, P = .005) and overall survival (OR = 2.0, P = .009). These results suggest that inflammasome genetic variants are important prognostic factors for the outcome of allo-SCT. If validated in larger studies, including unrelated allo-SCT, NLRPs genotype would become an important factor in donor selection.