Avelino Verceles - Academia.edu (original) (raw)
Papers by Avelino Verceles
Rationale: The COVID-19 pandemic disrupted non-COVID critical care trials globally as intensive c... more Rationale: The COVID-19 pandemic disrupted non-COVID critical care trials globally as intensive care units (ICUs) prioritized patient care and COVID-specific research. The international randomized controlled trial CYCLE (Critical Care Cycling to Improve Lower Extremity Strength) was forced to halt recruitment at all sites in March 2020, creating immediate challenges. We applied the CONSERVE (CONSORT and SPIRIT Extension for RCTs Revised in Extenuating Circumstance) guidance to report the impact of the pandemic on CYCLE and describe our mitigation approaches. Methods On March 23, 2020, the CYCLE Methods Centre distributed a standardized email to determine the number of patients still in-hospital and those requiring imminent 90-day endpoint assessments. We assessed protocol fidelity by documenting attempts to provide the in-hospital randomized intervention (cycling or routine physiotherapy), collect the primary outcome (physical function 3-days post-ICU discharge), and 90-day outcomes...
CHEST Journal, 2006
PURPOSE: We noted a difference in outcome between patients with Community Acquired Severe Sepsis ... more PURPOSE: We noted a difference in outcome between patients with Community Acquired Severe Sepsis (CASS) versus patients with Hospital Acquired Severe Sepsis (HASS) at our institution and designed a study of factors that might explain this difference. We choose to analyze patients with CASS admitted to the MICU via the Emergency Department (ED) compared to patient transfers from within the hospital into the MICU for HASS. Both patient groups were treated for Severe Sepsis (SS) with the same MICU standardized Sepsis Guideline. METHODS: The records of 53 MICU patients with SS, between June 2004 and March 2006, were retrospectively reviewed. Data collection included: a) initial location of each patient without prior hospitalization as the definition of CASS versus HASS, b) patient demographics, c) APACHE II scores, d) milestones of Early Goal Directed Therapy (EGDT) using our
CHEST Journal, 2005
PURPOSE: Although institutions worldwide are acknowledging the decrease in mortality from therapi... more PURPOSE: Although institutions worldwide are acknowledging the decrease in mortality from therapies presented within the Surviving Sepsis campaign, many have encountered major obstacles in implementation. At our tertiary care, University Hospital facility we devised a "hospital-centric" sepsis pathway using a multi-format educational approach. We believe an educational program emphasizing ways to identify patient signs and symptoms is a more efficient way to improve outcomes, rather than appropriating resources to a specialized team, such as a Rapid Response Team.
Background: The combination of neuromuscular electrical stimulation (NMES) with high protein supp... more Background: The combination of neuromuscular electrical stimulation (NMES) with high protein supplementation (HPRO) to preserve muscle mass and function has not been assessed in ICU patients. We compared the effects of a multimodal intervention combining NMES and HPRO with mobility and strength rehabilitation program (NMES+HPRO+PT) to standardized ICU care (SC). Methods: Over 14 days the SC group received usual critical care and rehabilitation while the NMES+HPRO+PT received 30 minutes NMES twice daily for 10 days applied to the quadriceps and dorsiflexors bilaterally and a mean 1.3±0.4 HPRO g/kg body weight in addition to SC. Nonresponsive patients received passive exercises and once responsive were encouraged to exercise actively. Primary outcome measures were muscle volume and cross-section area (CSA) measured using CT-imaging. Secondary outcomes included nutritional status, nitrogen balance, effect on delirium, and days on mechanical ventilation (MV).Results: On day 14, the NMES...
Journal of Vascular Surgery: Venous and Lymphatic Disorders, 2020
In this analysis of the ATTRACT Study, among patients with proximal DVT, pharmacomechanical cathe... more In this analysis of the ATTRACT Study, among patients with proximal DVT, pharmacomechanical catheter-directed thrombolysis (PCDT) with anticoagulation, compared with anticoagulation alone, had a beneficial effect on QOL during the first 6 months post-treatment (e.g. VEINES-QOL change scores were greater in PCDT vs. No PCDT from baseline to one month (difference 5.7; P=0.0006) and baseline to 6 months (5.1; P=0.0029). Further, among proximal DVT patients with iliofemoral DVT, this benefit was apparent over 24 months post-treatment. Take Home Message: Patients with iliofemoral DVT have a worse long-term prognosis (poorer QOL) than patients with femoral-popliteal DVT. Early use of pharmacomechanical catheter-directed thrombolysis improves QOL in patients with acute iliofemoral DVT and may be reasonable to consider in selected patients who have severe symptoms, low bleeding risk, and a willingness to undergo a catheter-based procedure, after careful discussion of the benefits and risks.
Critical care medicine, 2018
Clinicians caring for patients with intracerebral hemorrhage must often discuss prognosis and goa... more Clinicians caring for patients with intracerebral hemorrhage must often discuss prognosis and goals of care with their patients' surrogate decision makers, and may make numeric estimates of likelihood of survival and functional independence, informed by validated prediction models. Surrogates' prognostic estimates are often discordant with physicians', suggesting that physicians' numeric statements may not be accurately interpreted. We sought to assess the relationship between numeracy and interpretation of prognostic estimates in intracerebral hemorrhage among surrogate decision makers. We also assessed surrogates' application of prognostic estimates to decisions regarding goals of care. Single-center, survey-based, cross-sectional study. Twenty-two-bed neurologic ICU at an urban, academic hospital. Surrogate decision makers for patients admitted to the neurologic ICU. Participants completed a survey containing five clinical vignettes describing patients with no...
The Journal of international medical research, 2018
Objective Alcohol is a hypnotic that modifies immune function, specifically the cytokines interfe... more Objective Alcohol is a hypnotic that modifies immune function, specifically the cytokines interferon gamma (IFN-γ) and interleukin 2 (IL-2). We evaluated the association between unscheduled napping and acute alcohol-induced augmentation of IFN-γ and IL-2 expression. Methods In this prospective, observational pilot study, volunteers completed questionnaires on sleep quality, alcohol use, and hangover characteristics. Actigraph recordings began three nights before and continued for four nights after study initiation. Napping was recorded by actigraphy and self-reporting. A weight-based dose of 100-proof vodka was consumed, and the blood alcohol content (BAC) and phytohemagglutinin-M stimulated cytokine level were measured before and 20 minutes, 2 hours, and 5 hours after binge consumption. Results Ten healthy volunteers participated (mean age, 34.4 ± 2.3 years; mean body mass index, 23.9 ± 4.6 kg/m; 60% female). The mean 20-minute BAC was 137.7 ± 40.7 mg/dL. Seven participants took an...
Current Nutrition Reports, 2017
Purpose of Review The aim of this narrative review was to summarize the accuracy of predictive eq... more Purpose of Review The aim of this narrative review was to summarize the accuracy of predictive equations used to estimate energy expenditure in older, hospitalized adults. Recent Findings More than 50% of patients admitted to intensive care units are older adults. Currently accepted prediction equations used to determine energy intake in the older, hospitalized patient were not specifically developed for the aging population. Rates of multimorbidity, polypharmacy, and malnutrition, conditions that influence energy expenditure, are higher in older adults compared to younger adults. Summary For these reasons, current equations may not accurately assess energy needs in this population. As the evidence demonstrating the importance of nutritional supplementation in older, hospitalized adults grows, more accurate energy assessment methods that account for age-related conditions are needed to predict nutritional requirements.
Journal of critical care, Oct 27, 2017
The World Health Organization (WHO) has developed a simplified algorithm specific to resource-lim... more The World Health Organization (WHO) has developed a simplified algorithm specific to resource-limited settings for the treatment of severe sepsis emphasizing early fluids and antibiotics. However, this protocol's clinical effectiveness is unknown. We describe patient outcomes before and after implementation of an adapted WHO severe sepsis protocol at a community hospital in Haiti. Using a before-and-after study design, we retrospectively enrolled 99 adult Emergency Department patients with severe sepsis from January through March 2012. After protocol implementation in January 2014, we compared outcomes to 67 patients with severe sepsis retrospectively enrolled from February to April 2014. We defined sepsis according to the WHO's Integrated Management of Adult Illness guidelines and severe sepsis as sepsis plus organ dysfunction. After protocol implementation, quantity of fluid administered increased and the physician's differential diagnoses more often included sepsis. P...
Critical care medicine, 2017
American journal of critical care : an official publication, American Association of Critical-Care Nurses, 2016
A 62-year-old woman treated with several courses of corticosteroids for an undifferentiated rash ... more A 62-year-old woman treated with several courses of corticosteroids for an undifferentiated rash came to the emergency department with progressively worsening cutaneous signs and symptoms and generalized weakness. She had scabies, and despite treatment continued to decompensate. Repeat skin biopsies revealed disseminated herpes simplex virus infection, and results of blood cultures were consistent with infection by methicillin-resistant Staphylococcus aureus. Despite antiviral and antimicrobial therapy, sepsis and multiorgan failure developed, and the patient died. This case illustrates the complications of the rare entity eczema herpeticum, which occurs most often in immunocompromised patients and is associated with a high mortality. Maintaining a high index of suspicion for this disease in decompensating patients with an unidentified rash is essential to avoid catastrophic outcomes.
Journal of critical care, Jan 7, 2017
Ultrasound (US) is a burgeoning diagnostic tool and is often the only available imaging modality ... more Ultrasound (US) is a burgeoning diagnostic tool and is often the only available imaging modality in low- and middle-income countries (LMICs). However, bedside providers often lack training to acquire or interpret US images. We conducted a study to determine if a remote tele-intensivist could mentor geographically removed LMIC providers to obtain quality and clinically useful US images. Nine Haitian non-physician health care workers received a 20-minute training on basic US techniques. A volunteer was connected to an intensivist located in the USA via FaceTime. The intensivist remotely instructed the non-physicians to ultrasound five anatomic sites. The tele-intensivist evaluated the image quality and clinical utility of performing tele-ultrasound in a LMIC. The intensivist agreed (defined as "agree" or "strongly agree" on a five-point Likert scale) that 90% (57/63) of the FaceTime images were high quality. The intensivist felt comfortable making clinical decision...
Glycobiology, 2016
Neuraminidase-1 (NEU1) is the predominant sialidase expressed in human airway epithelia and lung ... more Neuraminidase-1 (NEU1) is the predominant sialidase expressed in human airway epithelia and lung microvascular endothelia where it mediates multiple biological processes. We tested whether the NEU1-selective sialidase inhibitor, C9-butyl-amide-2-deoxy-2,3-dehydro-N-acetylneuraminic acid (C9-BA-DANA), inhibits one or more established NEU1-mediated bioactivities in human lung cells. We established the IC 50 values of C9-BA-DANA for total sialidase activity in human airway epithelia, lung microvascular endothelia and lung fibroblasts to be 3.74 µM, 13.0 µM and 4.82 µM, respectively. In human airway epithelia, C9-BA-DANA dose-dependently inhibited flagellin-induced, NEU1-mediated mucin-1 ectodomain desialylation, adhesiveness for Pseudomonas aeruginosa and shedding. In lung microvascular endothelia, C9-BA-DANA reversed NEU1-driven restraint of cell migration into a wound and disruption of capillary-like tube formation. NEU1 and its chaperone/transport protein, protective protein/cathepsin A (PPCA), were differentially expressed in these same cells. Normalized NEU1 protein expression correlated with total sialidase activity whereas PPCA expression did not. In contrast to
Journal of investigative medicine high impact case reports
Introduction. Pulmonary arteriovenous malformations (PAVMs) have been associated with life-threat... more Introduction. Pulmonary arteriovenous malformations (PAVMs) have been associated with life-threatening complications, such as stroke and massive hemoptysis, thus posing significant morbidity if left untreated. We report a case of an incidental finding of a PAVM in a trauma patient newly recognized to have suspected hereditary hemorrhagic telangiectasia (HHT). Case Description. A 34-year-old man with a history of recurrent epistaxis presented with a sudden fall associated with seizure-like activity. Trauma imaging showed a large subdural hematoma and, incidentally, a serpiginous focus within the right upper lobe with a prominent feeding artery consistent with a PAVM. The patient was diagnosed with a simple PAVM related to possible or suspected HHT, an autosomal dominant trait with age-related penetrance. He underwent a pulmonary arteriography of the right upper and lower lobe with the use of a microcatheter system; however, the PAVM could not be visualized. Thus, he was managed medic...
Journal of Biological Chemistry, 2015
Background: Pseudomonas aeruginosa flagellin binds to the membrane-tethered mucin, MUC1. Results:... more Background: Pseudomonas aeruginosa flagellin binds to the membrane-tethered mucin, MUC1. Results: Flagellin drives NEU1 to desialylate MUC1, thereby increasing its adhesiveness for Pseudomonas aeruginosa and its shedding. Conclusion: P. aeruginosa hijacks host NEU1 through its flagellin. Significance: P. aeruginosa mobilizes NEU1 to enhance its pathogenicity, but the host retaliates by releasing MUC1 as a hyperadhesive decoy receptor. Airway epithelia express sialylated receptors that recognize exogenous danger signals. Regulation of receptor responsiveness to these signals remains incompletely defined. Here, we explore the mechanisms through which the human sialidase, neuraminidase-1 (NEU1), promotes the interaction between the sialoprotein, mucin 1 (MUC1), and the opportunistic pathogen, Pseudomonas aeruginosa. P. aeruginosa flagellin engaged the MUC1 ectodomain (ED), increasing NEU1 association with MUC1. The flagellin stimulus increased the association of MUC1-ED with both NEU1 and its chaperone/transport protein, protective protein/cathepsin A. Scatchard analysis demonstrated NEU1-dependent increased binding affinity of flagellin to MUC1-expressing epithelia. NEU1-driven MUC1-ED desialylation rapidly increased P. aeruginosa adhesion to and invasion of the airway epithelium. MUC1-ED desialylation also increased its shedding, and the shed MUC1-ED competitively blocked P. aeruginosa adhesion to cell-associated MUC1-ED. Levels of desialylated MUC1-ED were elevated in the bronchoalveolar lavage fluid of mechanically ventilated patients with P. aeruginosa airway colonization. Preincubation of P. aeruginosa with these same ex vivo fluids competitively inhibited bacterial adhesion to airway epithelia, and MUC1-ED immunodepletion completely abrogated their inhibitory activity. These data indicate that a prokaryote, P. aeruginosa, in a ligand-specific manner, mobilizes eukaryotic NEU1 to enhance bacterial pathogenicity, but the host retaliates by releasing MUC1-ED into the airway lumen as a hyperadhesive decoy receptor.
Clinical toxicology (Philadelphia, Pa.), Jan 17, 2015
B47. INTENSIVE CARE UNIT PHYSIOTHERAPY AND WEANING: MIND OVER MUSCLE?, 2012
Rationale: The COVID-19 pandemic disrupted non-COVID critical care trials globally as intensive c... more Rationale: The COVID-19 pandemic disrupted non-COVID critical care trials globally as intensive care units (ICUs) prioritized patient care and COVID-specific research. The international randomized controlled trial CYCLE (Critical Care Cycling to Improve Lower Extremity Strength) was forced to halt recruitment at all sites in March 2020, creating immediate challenges. We applied the CONSERVE (CONSORT and SPIRIT Extension for RCTs Revised in Extenuating Circumstance) guidance to report the impact of the pandemic on CYCLE and describe our mitigation approaches. Methods On March 23, 2020, the CYCLE Methods Centre distributed a standardized email to determine the number of patients still in-hospital and those requiring imminent 90-day endpoint assessments. We assessed protocol fidelity by documenting attempts to provide the in-hospital randomized intervention (cycling or routine physiotherapy), collect the primary outcome (physical function 3-days post-ICU discharge), and 90-day outcomes...
CHEST Journal, 2006
PURPOSE: We noted a difference in outcome between patients with Community Acquired Severe Sepsis ... more PURPOSE: We noted a difference in outcome between patients with Community Acquired Severe Sepsis (CASS) versus patients with Hospital Acquired Severe Sepsis (HASS) at our institution and designed a study of factors that might explain this difference. We choose to analyze patients with CASS admitted to the MICU via the Emergency Department (ED) compared to patient transfers from within the hospital into the MICU for HASS. Both patient groups were treated for Severe Sepsis (SS) with the same MICU standardized Sepsis Guideline. METHODS: The records of 53 MICU patients with SS, between June 2004 and March 2006, were retrospectively reviewed. Data collection included: a) initial location of each patient without prior hospitalization as the definition of CASS versus HASS, b) patient demographics, c) APACHE II scores, d) milestones of Early Goal Directed Therapy (EGDT) using our
CHEST Journal, 2005
PURPOSE: Although institutions worldwide are acknowledging the decrease in mortality from therapi... more PURPOSE: Although institutions worldwide are acknowledging the decrease in mortality from therapies presented within the Surviving Sepsis campaign, many have encountered major obstacles in implementation. At our tertiary care, University Hospital facility we devised a "hospital-centric" sepsis pathway using a multi-format educational approach. We believe an educational program emphasizing ways to identify patient signs and symptoms is a more efficient way to improve outcomes, rather than appropriating resources to a specialized team, such as a Rapid Response Team.
Background: The combination of neuromuscular electrical stimulation (NMES) with high protein supp... more Background: The combination of neuromuscular electrical stimulation (NMES) with high protein supplementation (HPRO) to preserve muscle mass and function has not been assessed in ICU patients. We compared the effects of a multimodal intervention combining NMES and HPRO with mobility and strength rehabilitation program (NMES+HPRO+PT) to standardized ICU care (SC). Methods: Over 14 days the SC group received usual critical care and rehabilitation while the NMES+HPRO+PT received 30 minutes NMES twice daily for 10 days applied to the quadriceps and dorsiflexors bilaterally and a mean 1.3±0.4 HPRO g/kg body weight in addition to SC. Nonresponsive patients received passive exercises and once responsive were encouraged to exercise actively. Primary outcome measures were muscle volume and cross-section area (CSA) measured using CT-imaging. Secondary outcomes included nutritional status, nitrogen balance, effect on delirium, and days on mechanical ventilation (MV).Results: On day 14, the NMES...
Journal of Vascular Surgery: Venous and Lymphatic Disorders, 2020
In this analysis of the ATTRACT Study, among patients with proximal DVT, pharmacomechanical cathe... more In this analysis of the ATTRACT Study, among patients with proximal DVT, pharmacomechanical catheter-directed thrombolysis (PCDT) with anticoagulation, compared with anticoagulation alone, had a beneficial effect on QOL during the first 6 months post-treatment (e.g. VEINES-QOL change scores were greater in PCDT vs. No PCDT from baseline to one month (difference 5.7; P=0.0006) and baseline to 6 months (5.1; P=0.0029). Further, among proximal DVT patients with iliofemoral DVT, this benefit was apparent over 24 months post-treatment. Take Home Message: Patients with iliofemoral DVT have a worse long-term prognosis (poorer QOL) than patients with femoral-popliteal DVT. Early use of pharmacomechanical catheter-directed thrombolysis improves QOL in patients with acute iliofemoral DVT and may be reasonable to consider in selected patients who have severe symptoms, low bleeding risk, and a willingness to undergo a catheter-based procedure, after careful discussion of the benefits and risks.
Critical care medicine, 2018
Clinicians caring for patients with intracerebral hemorrhage must often discuss prognosis and goa... more Clinicians caring for patients with intracerebral hemorrhage must often discuss prognosis and goals of care with their patients' surrogate decision makers, and may make numeric estimates of likelihood of survival and functional independence, informed by validated prediction models. Surrogates' prognostic estimates are often discordant with physicians', suggesting that physicians' numeric statements may not be accurately interpreted. We sought to assess the relationship between numeracy and interpretation of prognostic estimates in intracerebral hemorrhage among surrogate decision makers. We also assessed surrogates' application of prognostic estimates to decisions regarding goals of care. Single-center, survey-based, cross-sectional study. Twenty-two-bed neurologic ICU at an urban, academic hospital. Surrogate decision makers for patients admitted to the neurologic ICU. Participants completed a survey containing five clinical vignettes describing patients with no...
The Journal of international medical research, 2018
Objective Alcohol is a hypnotic that modifies immune function, specifically the cytokines interfe... more Objective Alcohol is a hypnotic that modifies immune function, specifically the cytokines interferon gamma (IFN-γ) and interleukin 2 (IL-2). We evaluated the association between unscheduled napping and acute alcohol-induced augmentation of IFN-γ and IL-2 expression. Methods In this prospective, observational pilot study, volunteers completed questionnaires on sleep quality, alcohol use, and hangover characteristics. Actigraph recordings began three nights before and continued for four nights after study initiation. Napping was recorded by actigraphy and self-reporting. A weight-based dose of 100-proof vodka was consumed, and the blood alcohol content (BAC) and phytohemagglutinin-M stimulated cytokine level were measured before and 20 minutes, 2 hours, and 5 hours after binge consumption. Results Ten healthy volunteers participated (mean age, 34.4 ± 2.3 years; mean body mass index, 23.9 ± 4.6 kg/m; 60% female). The mean 20-minute BAC was 137.7 ± 40.7 mg/dL. Seven participants took an...
Current Nutrition Reports, 2017
Purpose of Review The aim of this narrative review was to summarize the accuracy of predictive eq... more Purpose of Review The aim of this narrative review was to summarize the accuracy of predictive equations used to estimate energy expenditure in older, hospitalized adults. Recent Findings More than 50% of patients admitted to intensive care units are older adults. Currently accepted prediction equations used to determine energy intake in the older, hospitalized patient were not specifically developed for the aging population. Rates of multimorbidity, polypharmacy, and malnutrition, conditions that influence energy expenditure, are higher in older adults compared to younger adults. Summary For these reasons, current equations may not accurately assess energy needs in this population. As the evidence demonstrating the importance of nutritional supplementation in older, hospitalized adults grows, more accurate energy assessment methods that account for age-related conditions are needed to predict nutritional requirements.
Journal of critical care, Oct 27, 2017
The World Health Organization (WHO) has developed a simplified algorithm specific to resource-lim... more The World Health Organization (WHO) has developed a simplified algorithm specific to resource-limited settings for the treatment of severe sepsis emphasizing early fluids and antibiotics. However, this protocol's clinical effectiveness is unknown. We describe patient outcomes before and after implementation of an adapted WHO severe sepsis protocol at a community hospital in Haiti. Using a before-and-after study design, we retrospectively enrolled 99 adult Emergency Department patients with severe sepsis from January through March 2012. After protocol implementation in January 2014, we compared outcomes to 67 patients with severe sepsis retrospectively enrolled from February to April 2014. We defined sepsis according to the WHO's Integrated Management of Adult Illness guidelines and severe sepsis as sepsis plus organ dysfunction. After protocol implementation, quantity of fluid administered increased and the physician's differential diagnoses more often included sepsis. P...
Critical care medicine, 2017
American journal of critical care : an official publication, American Association of Critical-Care Nurses, 2016
A 62-year-old woman treated with several courses of corticosteroids for an undifferentiated rash ... more A 62-year-old woman treated with several courses of corticosteroids for an undifferentiated rash came to the emergency department with progressively worsening cutaneous signs and symptoms and generalized weakness. She had scabies, and despite treatment continued to decompensate. Repeat skin biopsies revealed disseminated herpes simplex virus infection, and results of blood cultures were consistent with infection by methicillin-resistant Staphylococcus aureus. Despite antiviral and antimicrobial therapy, sepsis and multiorgan failure developed, and the patient died. This case illustrates the complications of the rare entity eczema herpeticum, which occurs most often in immunocompromised patients and is associated with a high mortality. Maintaining a high index of suspicion for this disease in decompensating patients with an unidentified rash is essential to avoid catastrophic outcomes.
Journal of critical care, Jan 7, 2017
Ultrasound (US) is a burgeoning diagnostic tool and is often the only available imaging modality ... more Ultrasound (US) is a burgeoning diagnostic tool and is often the only available imaging modality in low- and middle-income countries (LMICs). However, bedside providers often lack training to acquire or interpret US images. We conducted a study to determine if a remote tele-intensivist could mentor geographically removed LMIC providers to obtain quality and clinically useful US images. Nine Haitian non-physician health care workers received a 20-minute training on basic US techniques. A volunteer was connected to an intensivist located in the USA via FaceTime. The intensivist remotely instructed the non-physicians to ultrasound five anatomic sites. The tele-intensivist evaluated the image quality and clinical utility of performing tele-ultrasound in a LMIC. The intensivist agreed (defined as "agree" or "strongly agree" on a five-point Likert scale) that 90% (57/63) of the FaceTime images were high quality. The intensivist felt comfortable making clinical decision...
Glycobiology, 2016
Neuraminidase-1 (NEU1) is the predominant sialidase expressed in human airway epithelia and lung ... more Neuraminidase-1 (NEU1) is the predominant sialidase expressed in human airway epithelia and lung microvascular endothelia where it mediates multiple biological processes. We tested whether the NEU1-selective sialidase inhibitor, C9-butyl-amide-2-deoxy-2,3-dehydro-N-acetylneuraminic acid (C9-BA-DANA), inhibits one or more established NEU1-mediated bioactivities in human lung cells. We established the IC 50 values of C9-BA-DANA for total sialidase activity in human airway epithelia, lung microvascular endothelia and lung fibroblasts to be 3.74 µM, 13.0 µM and 4.82 µM, respectively. In human airway epithelia, C9-BA-DANA dose-dependently inhibited flagellin-induced, NEU1-mediated mucin-1 ectodomain desialylation, adhesiveness for Pseudomonas aeruginosa and shedding. In lung microvascular endothelia, C9-BA-DANA reversed NEU1-driven restraint of cell migration into a wound and disruption of capillary-like tube formation. NEU1 and its chaperone/transport protein, protective protein/cathepsin A (PPCA), were differentially expressed in these same cells. Normalized NEU1 protein expression correlated with total sialidase activity whereas PPCA expression did not. In contrast to
Journal of investigative medicine high impact case reports
Introduction. Pulmonary arteriovenous malformations (PAVMs) have been associated with life-threat... more Introduction. Pulmonary arteriovenous malformations (PAVMs) have been associated with life-threatening complications, such as stroke and massive hemoptysis, thus posing significant morbidity if left untreated. We report a case of an incidental finding of a PAVM in a trauma patient newly recognized to have suspected hereditary hemorrhagic telangiectasia (HHT). Case Description. A 34-year-old man with a history of recurrent epistaxis presented with a sudden fall associated with seizure-like activity. Trauma imaging showed a large subdural hematoma and, incidentally, a serpiginous focus within the right upper lobe with a prominent feeding artery consistent with a PAVM. The patient was diagnosed with a simple PAVM related to possible or suspected HHT, an autosomal dominant trait with age-related penetrance. He underwent a pulmonary arteriography of the right upper and lower lobe with the use of a microcatheter system; however, the PAVM could not be visualized. Thus, he was managed medic...
Journal of Biological Chemistry, 2015
Background: Pseudomonas aeruginosa flagellin binds to the membrane-tethered mucin, MUC1. Results:... more Background: Pseudomonas aeruginosa flagellin binds to the membrane-tethered mucin, MUC1. Results: Flagellin drives NEU1 to desialylate MUC1, thereby increasing its adhesiveness for Pseudomonas aeruginosa and its shedding. Conclusion: P. aeruginosa hijacks host NEU1 through its flagellin. Significance: P. aeruginosa mobilizes NEU1 to enhance its pathogenicity, but the host retaliates by releasing MUC1 as a hyperadhesive decoy receptor. Airway epithelia express sialylated receptors that recognize exogenous danger signals. Regulation of receptor responsiveness to these signals remains incompletely defined. Here, we explore the mechanisms through which the human sialidase, neuraminidase-1 (NEU1), promotes the interaction between the sialoprotein, mucin 1 (MUC1), and the opportunistic pathogen, Pseudomonas aeruginosa. P. aeruginosa flagellin engaged the MUC1 ectodomain (ED), increasing NEU1 association with MUC1. The flagellin stimulus increased the association of MUC1-ED with both NEU1 and its chaperone/transport protein, protective protein/cathepsin A. Scatchard analysis demonstrated NEU1-dependent increased binding affinity of flagellin to MUC1-expressing epithelia. NEU1-driven MUC1-ED desialylation rapidly increased P. aeruginosa adhesion to and invasion of the airway epithelium. MUC1-ED desialylation also increased its shedding, and the shed MUC1-ED competitively blocked P. aeruginosa adhesion to cell-associated MUC1-ED. Levels of desialylated MUC1-ED were elevated in the bronchoalveolar lavage fluid of mechanically ventilated patients with P. aeruginosa airway colonization. Preincubation of P. aeruginosa with these same ex vivo fluids competitively inhibited bacterial adhesion to airway epithelia, and MUC1-ED immunodepletion completely abrogated their inhibitory activity. These data indicate that a prokaryote, P. aeruginosa, in a ligand-specific manner, mobilizes eukaryotic NEU1 to enhance bacterial pathogenicity, but the host retaliates by releasing MUC1-ED into the airway lumen as a hyperadhesive decoy receptor.
Clinical toxicology (Philadelphia, Pa.), Jan 17, 2015
B47. INTENSIVE CARE UNIT PHYSIOTHERAPY AND WEANING: MIND OVER MUSCLE?, 2012