Management of coagulopathy among patients with cirrhosis undergoing upper endoscopy and paracentesis: Persistent gaps and areas of consensus in a multispecialty Delphi.

Background and Aims Patients with cirrhosis have abnormal coagulation indices such as a high international normalized ratio (INR) and low platelet count, but these do not correlate well with peri-procedure bleeding risk. We sought to develop consensus among the multiple stakeholders in cirrhosis care to inform process measures that can help improve the quality of the peri-procedure management of coagulopathy in cirrhosis. Approach and Results We identified candidate process measures for peri-procedure coagulopathy management in multiple contexts relating to the performance of paracentesis and upper endoscopy. An 11-member panel with content expertise was convened. It included nominees from professional societies for interventional radiology, transfusion medicine, and anesthesia as well as representatives from hematology, emergency medicine, transplant surgery, and community practice. Each measure was evaluated for agreement using a modified Delphi approach (3 rounds of rating) to define the final set of measures. Out of 286 possible measures, 33 measures made the final set. INR testing was not required for diagnostic or therapeutic paracentesis as well as diagnostic endoscopy. Plasma transfusion should be avoided for all paracenteses and diagnostic endoscopy. No consensus was achieved for these items in therapeutic intent or emergent endoscopy. The risks of prophylactic platelet transfusions exceed their benefits for outpatient diagnostic paracentesis and when platelet counts >20,000/mm 3 . It is uncertain whether risks outweigh benefits below 20,000/mm 3 in other contexts. No consensus was achieved on whether it was permissible to continue or stop systemic anticoagulation. Continuous aspirin was permissible for each procedure. Clopidogrel was permissible for diagnostic and therapeutic paracentesis and diagnostic endoscopy. Conclusions We found many areas of consensus that may serve as a foundation for a common set of practice metrics for the peri-procedure management of coagulopathy in cirrhosis.

PAK1-dependent mechanotransduction enables myofibroblast nuclear adaptation and chromatin organization during fibrosis.

Myofibroblasts are responsible for scarring during fibrosis. The scar propagates mechanical signals inducing a radical transformation in myofibroblast cell state and increasing profibrotic phenotype. Here, we show mechanical stress from progressive scarring induces nuclear softening and de-repression of heterochromatin. The parallel loss of H3K9Me3 enables a permissive state for distinct chromatin accessibility and profibrotic gene regulation. Integrating chromatin accessibility profiles with RNA expression provides insight into the transcription network underlying the switch in profibrotic myofibroblast states, emphasizing mechanoadaptive regulation of PAK1 as key drivers. Through genetic manipulation in liver and lung fibrosis, loss of PAK1-dependent signaling impairs the mechanoadaptive response in vitro and dramatically improves fibrosis in vivo. Moreover, we provide human validation for mechanisms underpinning PAK1-mediated mechanotransduction in liver and lung fibrosis. Collectively, these observations provide insight into the nuclear mechanics driving the profibrotic chromatin landscape in fibrosis, highlighting actomyosin-dependent mechanisms as potential therapeutic targets in fibrosis.

Stability of executive function in children born at risk of neonatal hypoglycemia.

Executive function plays an important role in promoting learning and social-emotional development in children. Neonatal hypoglycemia associates with executive function difficulties at 4.5 years, but little is known about the development of executive function over time in children born at risk of neonatal hypoglycemia. We aimed to describe the stability of executive function from early to mid-childhood in children born at risk of neonatal hypoglycemia and its association with neonatal hypoglycemia. Participants in a prospective cohort study of infants born at risk for neonatal hypoglycemia were assessed at ages 2, 4.5, and 9-10 years. We assessed executive function with batteries of performance-based and questionnaire-based measures, and classified children into one of four stability groups (persistent typical, intermittent typical, intermittent difficulty, and persistent difficulty) based on dichotomized scores (typical versus low at each age). Multinomial logistic regression was used to determine the associations between neonatal hypoglycemia and executive function stability groups. Three hundred and nine children, of whom 197 (64%) experienced neonatal hypoglycemia were assessed. The majority of children had stable and typical performance-based (63%) and questionnaire-based (68%) executive function across all three ages. Around one-third (30-36%) of children had transient difficulties, and only a few (0.3-1.9%) showed persistent difficulties in executive function at all ages. There was no consistent evidence of an association between neonatal hypoglycemia and the stability of executive function. Neonatal hypoglycemia does not appear to predict a specific pattern of development of executive function in children born at risk.

Safety of curative-intent lung cancer surgery in older patients (octogenarians): A contemporary multicentre cohort study.

INTRODUCTION: Despite octogenarians representing an ever-increasing proportion of patients with lung cancer, there is a paucity of evidence describing outcomes after lung resection for these patients. We aimed to evaluate short and mid-term outcomes for octogenarians after lung resection. MATERIALS AND METHODS: A total of 5,470 consecutive patients undergoing lung resection for primary lung cancer from 2012-2019 in two UK centres were included. Primary outcomes were perioperative, 90-day, and one-year mortality in the octogenarian vs. non-octogenarian cohort. Appropriate statistical tests were used to compare outcomes between octogenarian and non-octogenarian patients. Secondary outcomes were post-operative complications and to validate the performance of the Thoracoscore model in the octogenarian cohort. RESULTS: Overall, 9.4% (n=513) of patients were aged ≥80. The rates of 90-day mortality, one-year mortality, and post-operative atrial fibrillation were significantly higher for octogenarians. The one-year mortality rate for octogenarians fell significantly over time (2012-2015: 16.5% vs 2016-2019: 10.2%, p=0.034). Subgroup analysis (2016-2019 only) demonstrated no significant difference in peri-operative, 90-day, or one-year mortality between octogenarian and non-octogenarian patients. Validation of the Thoracoscore model demonstrated modest discrimination and acceptable calibration. DISCUSSION: Mortality for octogenarians fell significantly over time in this study. Indeed, when confined to the most recent time period, comparable rates of both 90-day and one-year mortality for octogenarian and non-octogenarian patients were seen. Whilst preventative strategies to reduce the incidence of post-operative atrial fibrillation in octogenarians should be considered, these findings demonstrate that following appropriate patient selection, octogenarians can safely undergo lung resection for lung cancer.

Functional and Radiological Outcome of Short Same Segment Instrumentation in Thoracolumbar Burst fracture.

BACKGROUND: Thoracolumbar region is important biomechanics transition zone in which rigid thoracic and flexible lumbar spine meet. This area is highly vulnerable to traumatic spinal fracture.Among all spine fracture, compression type is most common and managed conservatively. Thoracolumbar spine fracture can be associated with neurological deficit, spinal instability. The optimal treatment for these injuries is still controversy and subject for research. METHODS: This retrospective study included 30 patients with single level thoracolumbar fracture.All the patients clinical and radiological parameters were evaluated preoperative, post-operative and 1 year follow up. Clinical parameters were included Visual analogue score, Oswestry disability index. Radiologic measurement were regional kyphotic angle by cobb's method and anterior vertebral body height loss (Mumford' santerior body compression equation method) in X-ray. All the data were analysed in SPSS version 20. RESULTS: A total of 30 patients were included in this study,19 were male.The mean age of the patients were 40.8±13.The main cause of injury was fall from height,26 patients. The most common level of fracture vertebra was L1,11 patients.The mean difference of preop and postop kyphosis was 11.70±50 with P<0.05.The mean difference of preop Oswestry disability index and postop Oswestry disability index score was 30.7±7.6 with T score 22(P<0.05).The preop and postop Visual analogue score score also improved ,mean difference was 2.8±1(P<0.05). CONCLUSIONS: Short segment instrumentation with placement of pedicle screw at fracture vertebra is one option in the treatment of thoracolumbar burst fracture.

Performance of alternative manual and automated deep learning segmentation techniques for the prediction of benign and malignant lung nodules.

Purpose: We aim to evaluate the performance of radiomic biopsy (RB), best-fit bounding box (BB), and a deep-learning-based segmentation method called no-new-U-Net (nnU-Net), compared to the standard full manual (FM) segmentation method for predicting benign and malignant lung nodules using a computed tomography (CT) radiomic machine learning model. Materials and Methods: A total of 188 CT scans of lung nodules from 2 institutions were used for our study. One radiologist identified and delineated all 188 lung nodules, whereas a second radiologist segmented a subset (n=20) of these nodules. Both radiologists employed FM and RB segmentation methods. BB segmentations were generated computationally from the FM segmentations. The nnU-Net, a deep-learning-based segmentation method, performed automatic nodule detection and segmentation. The time radiologists took to perform segmentations was recorded. Radiomic features were extracted from each segmentation method, and models to predict benign and malignant lung nodules were developed. The Kruskal-Wallis and DeLong tests were used to compare segmentation times and areas under the curve (AUC), respectively. Results: For the delineation of the FM, RB, and BB segmentations, the two radiologists required a median time (IQR) of 113 (54 to 251.5), 21 (9.25 to 38), and 16 (12 to 64.25) s, respectively (p=0.04). In dataset 1, the mean AUC (95% CI) of the FM, RB, BB, and nnU-Net model were 0.964 (0.96 to 0.968), 0.985 (0.983 to 0.987), 0.961 (0.956 to 0.965), and 0.878 (0.869 to 0.888). In dataset 2, the mean AUC (95% CI) of the FM, RB, BB, and nnU-Net model were 0.717 (0.705 to 0.729), 0.919 (0.913 to 0.924), 0.699 (0.687 to 0.711), and 0.644 (0.632 to 0.657). Conclusion: Radiomic biopsy-based models outperformed FM and BB models in prediction of benign and malignant lung nodules in two independent datasets while deep-learning segmentation-based models performed similarly to FM and BB. RB could be a more efficient segmentation method, but further validation is needed.

A Systematic Review of Sacral Insufficiency Fractures: Treatment Modalities and Outcomes.

Sacral insufficiency fractures can be managed conservatively, by surgical fixation or by sacroplasty. This systematic review compared the outcomes of different treatment modalities to ascertain the best. Studies included in this systematic review were those with sacral insufficiency fracture in elderly patients with some measure of outcomes reported. Fractures due to high-energy trauma or malignancy or in non-elderly patients were excluded. The review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE and Embase databases were searched from inception to January 6, 2022, yielding a total of 4299 papers of which 35 were eligible for inclusion. Pain reduction following sacroplasty (Visual Analogue Scale (VAS) difference 5.83, SD 1.14, n = 901) was superior compared with conservative management (VAS difference 3.7, SD 2.71, n = 65) (p <0.0001) and surgical fixation (with screws/rods +/- cement augmentation; VAS difference 4.1, SD 1.106, n = 154) (p< 0.001). There was no significant difference between pain relief following screw fixation and after conservative management (p = 0.1216). Hospital stay duration was shorter following sacroplasty (4.1 days )SD 3.9)) versus fixation (10.3 days (SD 5.59)) (p= 0.0001). Available evidence points to sacroplasty resulting in better pain relief and shorter hospital stay than other treatment options.

Challenges, Barriers, and Successes of Standardized Report Templates: Results of a Society of Interventional Radiology Survey.

Registry data are being increasingly used to establish treatment guidelines, set benchmarks, allocate resources, and make payment decisions. Although many registries rely on manual data entry, the Society of Interventional Radiology (SIR) is using automated data extraction for its VIRTEX registry. This process relies on participants using consistent terminology with highly structured data in physician-developed standardized reports (SR). To better understand barriers to adoption, a survey was sent to 3,178 SIR members. Responses were obtained from 451 interventional radiology practitioners (14.2%) from 92 unique academic and 151 unique private practices. Of these, 75% used structured reports and 32% used the SIR SR. The most common barriers to the use of these reports include SR length (35% of respondents), lack of awareness about the SR (31%), and lack of agreement on adoption within practices (27%). The results demonstrated insights regarding barriers in the use and/or adoption of SR and potential solutions.

A History and Modern Framework for Quality Improvement in Interventional Radiology.

Quality improvement (QI) initiatives have benefited patients as well as the broader practice of medicine. Large-scale QI has been facilitated by multi-institutional data registries, many of which were formed out of national or international medical society initiatives. With broad participation, QI registries have provided benefits that include but are not limited to establishing treatment guidelines, facilitating research related to uncommon procedures and conditions, and demonstrating the fiscal and clinical value of procedures for both medical providers and health systems. Because of the benefits offered by these databases, Society of Interventional Radiology (SIR) and SIR Foundation have committed to the development of an interventional radiology (IR) clinical data registry known as VIRTEX. A large IR database with participation from a multitude of practice environments has the potential to have a significant positive impact on the specialty through data-driven advances in patient safety and outcomes, clinical research, and reimbursement. This article reviews the current landscape of societal QI programs, presents a vision for a large-scale IR clinical data registry supported by SIR, and discusses the anticipated results that such a framework can produce.

Associations Between Autism Spectrum Quotient and Integration of Visual Stimuli in 9-year-old Children: Preliminary Evidence of Sex Differences.

PURPOSE: The dorsal stream vulnerability hypothesis posits that the dorsal stream, responsible for visual motion and visuo-motor processing, may be particularly vulnerable during neurodevelopment. Consistent with this, autism spectrum disorder (ASD) has been associated with deficits in global motion integration, though deficits in ventral stream tasks, such as form identification, have also been reported. In the current study, we examined whether a similar pattern of results is found in a cohort of 381 children born with neurodevelopmental risk factors and exhibiting a wide spectrum of caregiver-reported autistic traits. METHODS: We examined the associations between global motion perception, global form perception, fine motor function, visual-motor integration, and autistic traits (autism spectrum quotient, AQ) using linear regression, accounting for possible interactions with sex and other factors relevant to neurodevelopment. RESULTS: All assessments of dorsal stream function were significantly associated with AQ such that worse performance predicted higher AQ scores. We also observed a significant sex interaction, with worse global form perception associated with higher AQ in boys (n = 202) but not girls (n = 179). CONCLUSION: We found widespread associations between dorsal stream functions and autistic traits. These associations were observed in a large group of children with a range of AQ scores, demonstrating a range of visual function across the full spectrum of autistic traits. In addition, ventral function was associated with AQ in boys but not girls. Sex differences in the associations between visual processing and neurodevelopment should be considered in the designs of future studies.

Rapid Generation of Pulmonary Organoids from Induced Pluripotent Stem Cells by Co-Culturing Endodermal and Mesodermal Progenitors for Pulmonary Disease Modelling.

Differentiation of induced pluripotent stem cells to a range of target cell types is ubiquitous in monolayer culture. To further improve the phenotype of the cells produced, 3D organoid culture is becoming increasingly prevalent. Mature organoids typically require the involvement of cells from multiple germ layers. The aim of this study was to produce pulmonary organoids from defined endodermal and mesodermal progenitors. Endodermal and mesodermal progenitors were differentiated from iPSCs and then combined in 3D Matrigel hydrogels and differentiated for a further 14 days to produce pulmonary organoids. The organoids expressed a range of pulmonary cell markers such as SPA, SPB, SPC, AQP5 and T1α. Furthermore, the organoids expressed ACE2 capable of binding SARS-CoV-2 spike proteins, demonstrating the physiological relevance of the organoids produced. This study presented a rapid production of pulmonary organoids using a multi-germ-layer approach that could be used for studying respiratory-related human conditions.

Medical and social determinants of health as predictors of adverse outcomes in patients with inflammatory bowel disease.

There is a growing recognition that social determinants of health (SDOH) influence outcomes in patients with chronic diseases. This study aimed to investigate the influence of SDOH on outcomes in patients with inflammatory bowel disease (IBD). We conducted a retrospective cohort study of adult patients with IBD from 1996 to 2019. Patients were identified using ICD-10 codes for ulcerative colitis and Crohn's disease, and chart review was performed to validate the diagnosis and extract clinical information. SDOH factors including food security, financial resources, and transportation were self-reported by the patient. Random forest models were trained and tested in R to predict either IBD-related hospitalization or surgery. A total of 175 patients were studied, and the majority reported no financial resource, food security, or transportation concerns. For the model using clinical predictors, the sensitivity was 0.68 and specificity was 0.77 with an area under the receiver operating characteristic curve (AUROC) of 0.77. The model's performance did not significantly improve with the addition of SDOH information (AUROC of 0.78); however, model performance did vary by phenotype (AUROC of 0.86 for patients with Crohn's disease and AUROC of 0.68 for patients with ulcerative colitis). Further research is needed to understand the role of SDOH factors and IBD-related outcomes.

Executive function and behaviour problems in school-age children born at risk of neonatal hypoglycaemia.

AIM: To examine the relationship between neonatal hypoglycaemia and specific areas of executive function and behaviour in mid-childhood. METHOD: Participants in a prospective cohort study of infants born late preterm or at term at risk of neonatal hypoglycaemia were assessed at 9 to 10 years. We assessed executive function using performance-based (Cambridge Neuropsychological Tests Automated Battery) and questionnaire-based (Behavior Rating Inventory of Executive Function) measures and behaviour problems with the Strengths and Difficulties Questionnaire. Data are reported as adjusted odds ratio (aOR) with 95% confidence intervals, and standardized regression coefficients. RESULTS: We assessed 480 (230 females, 250 males; mean age 9 years 5 months [SD 4 months, range 8 years 8 months-11 years 0 months]) of 587 eligible children (82%). There were no differences in performance-based executive function between children who did and did not experience neonatal hypoglycaemia (blood glucose <2.6 mmoL/L). However, children who experienced hypoglycaemia, especially if severe or recurrent, were at greater risk of parent-reported metacognition difficulties (aOR 2.37-3.71), parent-reported peer (aOR 1.62-1.89) and teacher-reported conduct (aOR 2.14 for severe hypoglycaemia) problems. Both performance- and questionnaire-based executive functions were associated with behaviour problems. INTERPRETATION: Neonatal hypoglycaemia may be associated with difficulties in specific aspects of parent-reported executive functions and behaviour problems in mid-childhood.

Topological data analysis of thoracic radiographic images shows improved radiomics-based lung tumor histology prediction.

Topological data analysis provides tools to capture wide-scale structural shape information in data. Its main method, persistent homology, has found successful applications to various machine-learning problems. Despite its recent gain in popularity, much of its potential for medical image analysis remains undiscovered. We explore the prominent learning problems on thoracic radiographic images of lung tumors for which persistent homology improves radiomic-based learning. It turns out that our topological features well capture complementary information important for benign versus malignant and adenocarcinoma versus squamous cell carcinoma tumor prediction while contributing less consistently to small cell versus non-small cell-an interesting result in its own right. Furthermore, while radiomic features are better for predicting malignancy scores assigned by expert radiologists through visual inspection, we find that topological features are better for predicting more accurate histology assessed through long-term radiology review, biopsy, surgical resection, progression, or response.

Mid-Childhood Outcomes after Dextrose Gel Treatment of Neonatal Hypoglycaemia: Follow-Up of the Sugar Babies Randomized Trial.

INTRODUCTION: Dextrose gel is widely used as first-line treatment for neonatal hypoglycaemia given its cost-effectiveness and ease of use. The Sugar Babies randomized trial first showed that 40% dextrose gel was more effective in reversing hypoglycaemia than feeding alone. Follow-up of the Sugar Babies Trial cohort at 2 and 4.5 years of age reported that dextrose gel appeared safe, with similar rates of neurosensory impairment in babies randomized to dextrose or placebo gel. However, some effects of neonatal hypoglycaemia may not become apparent until school age. METHODS: Follow-up of the Sugar Babies Trial cohort at 9-10 years of age was reported. The primary outcome was low educational achievement in reading or mathematics. Secondary outcomes included other aspects of educational achievement, executive function, visual-motor function, and psychosocial adaptation. RESULTS: Of 227 eligible children, 184 (81%) were assessed at a mean (SD) age of 9.3 (0.2) years. Low educational achievement was similar in dextrose and placebo groups (36/86 [42%] vs. 42/94 [45%]; RR 1.04, 95% CI 0.76, 1.44; p = 0.79). Children allocated to dextrose gel had lower visual perception standard scores (95.2 vs. 100.6; MD -5.68, 95% CI -9.79, -1.57; p = 0.006) and a greater proportion had low (<85) visual perception scores (20/88 [23%] vs. 10/95 [11%]; RR 2.23, 95% CI 1.13, 4.37; p = 0.02). Other secondary outcomes, including other aspects of visual-motor function, were similar in both groups. CONCLUSION: Treatment dextrose gel does not appear to result in any clinically significant differences in educational achievement or other neurodevelopmental outcomes at mid-childhood.

Extracellular Matrix Secretion Mechanically Reinforces Interlocking Interfaces.

Drawing inspiration for biomaterials from biological systems has led to many biomedical innovations. One notable bioinspired device, Velcro, consists of two substrates with interlocking ability. Generating reversibly interlocking biomaterials is an area of investigation, as such devices can allow for modular tissue engineering, reversibly interlocking biomaterial interfaces, or friction-based coupling devices. Here, a biaxially interlocking interface generated using electrostatic flocking is reported. Two electrostatically flocked substrates are mechanically and reversibly interlocked with the ability to resist shearing and compression forces. An initial high-throughput screen of polyamide flock fibers with varying diameters and fiber lengths is conducted to elucidate the roles of different fiber parameters on scaffold mechanical properties. After determining the most desirable parameters via weight scoring, polylactic acid (PLA) fibers are used to emulate the ideal scaffold for in vitro use. PLA flocked scaffolds are populated with osteoblasts and interlocked. Interlocked flocked scaffolds improved cell survivorship under mechanical compression and sustained cell viability and proliferation. Additionally, the compression and shearing resistance of cell-seeded interlocking interfaces increased with increasing extracellular matrix deposition. The introduction of extracellular matrix-reinforced interlocking interfaces may serve as binders for modular tissue engineering, act as scaffolds for engineering tissue interfaces, or enable friction-based couplers for biomedical applications.

Diagnostic dilemma in hyperechoic breast masses.

Hyperechoic breast lesions are relatively uncommon, constituting only 0.6-6% of all breast masses and 0.6% of all biopsied lesions. The majority of these lesions are benign. There are rare malignancies that can present as hyperechoic masses and careful ultrasonographic assessment must be employed to avoid misdiagnosis.[1] We discuss the case of a 67-year-old female patient with a strong family history of breast and ovarian cancer, who presented with one such rare breast cancer in a hyperechoic mass.

Audit of Clinical Care Received by COVID-19 Patients Treated at a Tertiary Care Hospital of Nepal in 2021.

Like the world over, Nepal was also hard hit by the second wave of COVID-19. We audited the clinical care provided to COVID-19 patients admitted from April to June 2021 in a tertiary care hospital of Nepal. This was a cohort study using routinely collected hospital data. There were 620 patients, and most (458, 74%) had severe illness. The majority (600, 97%) of the patients were eligible for admission as per national guidelines. Laboratory tests helping to predict the outcome of COVID-19, such as D-dimer and C-reactive protein, were missing in about 25% of patients. Nearly all (>95%) patients with severe disease received corticosteroids, anticoagulants and oxygen. The use of remdesivir was low (22%). About 70% of the patients received antibiotics. Hospital exit outcomes of most (>95%) patients with mild and moderate illness were favorable (alive and discharged). Among patients with severe illness, about 25% died and 4% were critically ill, needing further referral. This is the first study from Nepal to audit and document COVID-19 clinical care provision in a tertiary care hospital, thus filling the evidence gap in this area from resource-limited settings. Adherence to admission guidelines was excellent. Laboratory testing, access to essential drugs and data management needs to be improved.

Differential responses of COPD macrophages to respiratory bacterial pathogens.

COPD patients have increased susceptibility to airway bacterial colonisation. Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae are three of the most common respiratory bacterial species in COPD. H. influenzae colonisation, but not other bacteria, in COPD patients is associated with higher sputum neutrophil counts. Alveolar macrophages are key in clearance of bacteria as well as releasing mediators to recruit and activate other immune cells in response to infection. The aim was to characterise differences in COPD macrophage responses to H. influenzae, M. catarrhalis and S. pneumoniae, focusing on release of inflammatory and chemotactic mediators, and apoptosis regulation. Lung macrophages and monocyte-derived macrophages from COPD patients and control subjects were exposed to H. influenzae, M. catarrhalis or S. pneumoniae. Cytokine secretion (tumour necrosis factor-α, interleukin (IL)-6, CXCL8, CCL5 and IL-1ß) were measured by ELISA and quantitative reverse transcriptase PCR (RT-qPCR), and apoptosis genes MCL-1, BCL-2, BAX and BAK1 by RT-qPCR. Apoptosis and reactive oxygen species (ROS) release were also measured. Macrophages responded differentially to the bacterial species, with increased, prolonged production of the neutrophil chemoattractant CXCL8 in response to H. influenzae and M. catarrhalis but not S. pneumoniae. S. pneumoniae initiated macrophage apoptosis and ROS release, H. influenzae and M. catarrhalis did not and increased anti-apoptosis gene expression (BCL-2 5.5-fold and MCL-1 2.4-fold, respectively). Differential cytokine responses of macrophages to these bacterial species can explain neutrophilic airway inflammation associated with H. influenzae, but not S. pneumoniae in COPD. Furthermore, delayed macrophage apoptosis is a potential mechanism contributing to inability to clear H. influenzae.