This document summarizes a study on the effects of coenzyme Q10 supplementation in patients with heart failure. The study included 107 patients with stable congestive heart failure who received 100 mg of CoQ10 per day for 12 weeks. Key results included a mild decrease in blood pressure and heart rate, weight loss, improvement in symptoms for 63% of patients, and 14% of patients moving to a lower NYHA class. Ejection fraction increased from 25.7% to 29.2% on average. Walking distance improved by 45.7% on average. The Karnofsky scale score improved from 57.7 to 63.2 on average. The study concluded that CoQ10 supplementation improved both clinical and physiological
This study examined the incidence, predictors, and impact of acute renal failure (ARF) following lung transplantation. The researchers retrospectively reviewed 296 patients who underwent lung transplantation at their medical center between 1992 and 2000. They found that ARF occurred in 56% of patients, though most cases did not require dialysis. Independent predictors of ARF requiring dialysis included lower baseline kidney function, diagnoses other than COPD, longer duration of mechanical ventilation, and use of the antifungal medication amphotericin B. Both ARF requiring dialysis and not requiring dialysis were associated with longer hospital stays, longer ventilation times, and increased early mortality compared to patients without ARF. ARF requiring dialysis was also associated with significantly lower
Napcon 2014 presentation abstract Page 14 - Presentation28
High Dose Rate Endobronchial Brachytherapy for Palliative Treatment of Lung Cancer – A Case Report Muhammed Aslam N K , Rajeev Ram , Achuthan V , Manoj D K ,Rajani M Pariyaram medical colleg , kannur
This case report describes an adolescent male with near fatal asthma who was unresponsive to conventional therapy and required rescue therapy. He presented with severe hypoxemia, hypercapnia, and acidosis. Despite aggressive management including mechanical ventilation, his condition deteriorated further with the development of barotrauma and hemodynamic instability. The introduction of extracorporeal membrane oxygenation (ECMO) dramatically improved his gas exchange and lung mechanics. ECMO allowed his lungs time to recover from inflammation while minimizing ventilator-induced injury. With ECMO support for 72 hours, the patient was successfully weaned from ventilation and made a full recovery.
Goal directed resuscitation for patientsDrJawad Butt
In this randomized controlled trial conducted across 51 centers, 792 patients with early septic shock who were randomized to receive early goal-directed therapy (EGDT) were compared to 796 patients receiving usual care. The primary outcome of all-cause mortality at 90 days was 18.6% in the EGDT group and 18.8% in the usual care group, showing no significant difference between the groups. Secondary and tertiary outcomes also showed no differences. The findings suggest that EGDT does not offer a survival advantage over usual care for patients presenting with early septic shock.
This document provides the definition and classification of acute kidney injury (AKI) put forth by the Kidney Disease: Improving Global Outcomes (KIDGO) group. It defines AKI as an abrupt reduction in kidney function seen within 48 hours that can be identified by an increase in serum creatinine of 0.3 mg/dL or 1.5 times the baseline level. AKI is classified into 3 stages based on the level of increase in serum creatinine and the urine output amount. The definition and staging criteria aim to provide a standardized approach for identifying and classifying AKI severity in clinical practice, research, and public health monitoring.
This study evaluated the outcomes of hepatic resection (HR) versus percutaneous tube drainage (PD) for patients with pyogenic liver abscesses and an APACHE II score ≥15. The study found that patients who underwent HR had significantly lower mortality, failure, and double treatment rates compared to those who only underwent PD. HR patients also had significantly shorter hospital stays, shorter duration of antibiotic use, and fewer procedure-related complications. The study concludes that aggressive HR may produce better clinical outcomes than PD alone for patients with severe liver abscesses as indicated by high APACHE II scores.
This document provides guidelines for the management of severe sepsis and septic shock last updated in 2008. A consensus committee of 68 international experts from 30 organizations used the GRADE methodology to develop recommendations based on a review of the literature. Key recommendations include early quantitative resuscitation, blood cultures before antibiotics, source control within 12 hours, broad-spectrum antibiotics within 1 hour for septic shock, targeting a mean arterial pressure of 65 mmHg with norepinephrine, and low tidal volume ventilation for acute respiratory distress syndrome. The guidelines are intended to improve outcomes for patients with severe sepsis and septic shock worldwide.
This study examined the incidence, predictors, and impact of acute renal failure (ARF) following lung transplantation. The researchers retrospectively reviewed 296 patients who underwent lung transplantation at their medical center between 1992 and 2000. They found that ARF occurred in 56% of patients, though most cases did not require dialysis. Independent predictors of ARF requiring dialysis included lower baseline kidney function, diagnoses other than COPD, longer duration of mechanical ventilation, and use of the antifungal medication amphotericin B. Both ARF requiring dialysis and not requiring dialysis were associated with longer hospital stays, longer ventilation times, and increased early mortality compared to patients without ARF. ARF requiring dialysis was also associated with significantly lower
Napcon 2014 presentation abstract Page 14 - Presentation28
High Dose Rate Endobronchial Brachytherapy for Palliative Treatment of Lung Cancer – A Case Report Muhammed Aslam N K , Rajeev Ram , Achuthan V , Manoj D K ,Rajani M Pariyaram medical colleg , kannur
This case report describes an adolescent male with near fatal asthma who was unresponsive to conventional therapy and required rescue therapy. He presented with severe hypoxemia, hypercapnia, and acidosis. Despite aggressive management including mechanical ventilation, his condition deteriorated further with the development of barotrauma and hemodynamic instability. The introduction of extracorporeal membrane oxygenation (ECMO) dramatically improved his gas exchange and lung mechanics. ECMO allowed his lungs time to recover from inflammation while minimizing ventilator-induced injury. With ECMO support for 72 hours, the patient was successfully weaned from ventilation and made a full recovery.
Goal directed resuscitation for patientsDrJawad Butt
In this randomized controlled trial conducted across 51 centers, 792 patients with early septic shock who were randomized to receive early goal-directed therapy (EGDT) were compared to 796 patients receiving usual care. The primary outcome of all-cause mortality at 90 days was 18.6% in the EGDT group and 18.8% in the usual care group, showing no significant difference between the groups. Secondary and tertiary outcomes also showed no differences. The findings suggest that EGDT does not offer a survival advantage over usual care for patients presenting with early septic shock.
This document provides the definition and classification of acute kidney injury (AKI) put forth by the Kidney Disease: Improving Global Outcomes (KIDGO) group. It defines AKI as an abrupt reduction in kidney function seen within 48 hours that can be identified by an increase in serum creatinine of 0.3 mg/dL or 1.5 times the baseline level. AKI is classified into 3 stages based on the level of increase in serum creatinine and the urine output amount. The definition and staging criteria aim to provide a standardized approach for identifying and classifying AKI severity in clinical practice, research, and public health monitoring.
This study evaluated the outcomes of hepatic resection (HR) versus percutaneous tube drainage (PD) for patients with pyogenic liver abscesses and an APACHE II score ≥15. The study found that patients who underwent HR had significantly lower mortality, failure, and double treatment rates compared to those who only underwent PD. HR patients also had significantly shorter hospital stays, shorter duration of antibiotic use, and fewer procedure-related complications. The study concludes that aggressive HR may produce better clinical outcomes than PD alone for patients with severe liver abscesses as indicated by high APACHE II scores.
This document provides guidelines for the management of severe sepsis and septic shock last updated in 2008. A consensus committee of 68 international experts from 30 organizations used the GRADE methodology to develop recommendations based on a review of the literature. Key recommendations include early quantitative resuscitation, blood cultures before antibiotics, source control within 12 hours, broad-spectrum antibiotics within 1 hour for septic shock, targeting a mean arterial pressure of 65 mmHg with norepinephrine, and low tidal volume ventilation for acute respiratory distress syndrome. The guidelines are intended to improve outcomes for patients with severe sepsis and septic shock worldwide.
Early goal-directed therapy in severe sepsis and septic shock: ProCESS, ARISE...Moh'd sharshir
1) This study compared early goal-directed therapy (EGDT) to usual care in patients with septic shock. EGDT aimed to optimize tissue oxygen delivery through monitoring of physiological targets like central venous pressure and central venous oxygen saturation.
2) The study found no significant difference in 90-day mortality between the EGDT and usual care groups. Patients in the EGDT group received more intravenous fluids and vasopressors but this did not impact mortality outcomes.
3) The study concludes that EGDT did not decrease mortality in patients presenting with septic shock compared to usual resuscitation practices. The value of incorporating EGDT into international guidelines is questionable.
Transcatheter intraarterial infusion of rt pa forHans Garcia
This study evaluated the success and complication rates of using intraarterial recombinant tissue-type plasminogen activator (rt-PA) infusion to treat acute lower extremity artery and bypass graft occlusions in 74 limbs of 70 patients. Thrombolytic success, defined as 95% thrombolysis and return of blood flow, was achieved in 86% of cases. Major bleeding complications occurred in 47% of patients, including bleeding at vascular access sites in 22 patients and remote bleeding in 7 patients. Despite the significant bleeding complications, 30-day mortality was 1% and amputation rate was 6%, resulting in a favorable 30-day amputation-free survival rate of 93%.
Damage control resuscitation (DCR) evolved from the concept of damage control surgery. It involves early blood product transfusions using a 1:1:1 ratio of red blood cells, plasma, and platelets to address trauma-induced coagulopathy. It also focuses on immediately arresting hemorrhage, restoring blood volume, and correcting physiological abnormalities like hypothermia and acidosis. DCR can be applied anywhere to critically injured patients. Massive transfusion protocols that guide DCR have been shown to improve survival rates in patients with severe injuries and hemorrhage. While DCR leaves surgical repairs incomplete initially, it buys time to stabilize patients sufficiently to allow for definitive care later.
New class of therapeutic agents called soluble guanylate cyclase (sGC) stimulators.
Impairment of NO synthesis and signaling through the NO-sGC–cGMP pathway is involved in the pathogenesis of pulmonary hypertension.
Dual mode of action,
Directly stimulating sGC independently of NO, and
Increasing the sensitivity of sGC to NO.
vasorelaxation , antiproliferative and antifibrotic effects
Comparison of two fluid management strategies in acute lung injuryDang Thanh Tuan
A randomized clinical trial compared a conservative fluid management strategy to a liberal strategy in patients with acute lung injury. The conservative strategy aimed to decrease lung edema by restricting fluid intake and increasing urine output, while the liberal strategy allowed more fluid administration. The primary outcome was 60-day mortality, with secondary outcomes including lung function and organ failures. The conservative strategy improved lung function and shortened time on ventilation and in the ICU without increasing other organ failures, though it did not significantly impact mortality.
Early Goal-Directed Therapy in Septic Shockshivabirdi
Early goal directed therapy (EGDT) aims to balance oxygen delivery and demand through manipulating cardiac preload, afterload and contractility using measures like lactate, base deficit and ScvO2. A study of 263 patients with severe sepsis or septic shock found that those receiving EGDT in the emergency department for at least 6 hours had significantly lower in-hospital, 28-day and 60-day mortality compared to standard therapy. EGDT also resulted in fewer organ dysfunctions, less coagulation abnormalities and cardiovascular collapse.
This randomized controlled trial evaluated the cardiovascular safety of semaglutide, a glucagon-like peptide-1 analogue, in patients with type 2 diabetes at high risk of cardiovascular events. The trial involved 3297 patients who were randomized to receive either once-weekly subcutaneous semaglutide (0.5 mg or 1.0 mg) or placebo for 104 weeks. The primary outcome was the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. The trial found that semaglutide was noninferior to placebo for the primary cardiovascular outcome and was associated with a significantly lower rate of the primary outcome compared to placebo. Rates of retinopathy complications were higher but rates of new or worse
This meta-analysis reviewed 5 randomized controlled trials involving 4,303 patients to determine if early goal-directed therapy (EGDT) according to Surviving Sepsis Campaign guidelines improves mortality outcomes in patients with severe sepsis or septic shock. The studies showed no statistically significant difference in 28-day, 60-day, or 90-day mortality between patients who received EGDT and those who received usual care. Secondary outcomes like hospital length of stay and need for organ support also did not differ significantly between the two groups. While EGDT decreased mortality, the effect was not statistically significant.
PROSEVA trial - Prone position in severe ARDS.
Why did prone position improve outcome of ARDS while other measures aimed at improving oxygenation such as high PEEP, RM and HFO have failed to do so?
The Emerging Role of BIomarkers and Bio-Impedancedrucsamal
This document discusses methods for assessing hydration status in patients with acute heart failure. It reviews classical assessment methods like history, physical exam, imaging techniques, and isotopic tracers, which is the gold standard but impractical. It then focuses on emerging roles of biomarkers and bioimpedance analysis which provide a less invasive way to estimate total body water content and fluid overload. These novel methods show promise for diagnosing, risk-stratifying, and guiding treatment decisions for acute heart failure patients.
The document discusses definitions, recognition, and interventions for sepsis. It begins by defining sepsis, severe sepsis, and septic shock according to the American College of Chest Physicians and Society of Critical Care Medicine. It then provides diagnostic criteria for systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic shock. The document discusses early goal-directed therapy (EGDT) as proven to reduce mortality in severe sepsis/septic shock. It outlines the Surviving Sepsis Care Bundles that are meant to be completed within 3 and 6 hours. The document discusses several studies related to sepsis management including lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy and the findings that cardiac filling pressures are
This document summarizes two studies on percutaneous left ventricular assist devices (LVADs) and coronary artery fistulas.
The first study investigated the ability of a percutaneous LVAD to deliver blood to the systemic circulation during cardiac arrest in pigs. The LVAD maintained blood flow and preferentially perfused vital organs like the brain. Intensified fluid loading further improved LVAD performance.
The second study evaluated the microvascular effects of ultrasound contrast (Definity) in hamsters with conditions like ischemia-reperfusion, diabetes, and sepsis. Inflammatory responses were higher in diabetes with ischemia and sepsis groups, independent of contrast use. Contrast did not alter hemodynamics or reology.
Understanding Antibiotics in Critically Ill Surgical PatientsAllison Boyd
1) The document discusses antibiotic stewardship principles, pharmacokinetic and pharmacodynamic changes in trauma and burn patients, and treatment recommendations for pneumonia and other infections in critically ill surgical patients.
2) It provides an overview of augmented renal clearance in trauma patients, inflammatory responses in burn patients, and how these physiologic changes can impact antibiotic dosing.
3) Guidelines for empiric treatment of pneumonia, including community-acquired pneumonia, hospital-acquired pneumonia, and ventilator-associated pneumonia, are reviewed based on risk factors and timing of infection onset.
Pearls about NSAIDs and their usage in the managaement of chronic pain, considering safety profile of both selective cox-2 or non selective cox-2 inhibitors
Autologous mononuclear and mesenchymal stromal cells infusion in COPD patients: impact on pulmonary capacity and quality of life in a Phase I randomized clinical trial
Identification of wave free period in the cardiac cycleRamachandra Barik
In the first part of this study, we identified the existence
of a diastolic interval in which intracoronary resistance at
rest is equivalent to time-averaged resistance during FFR
measurements. We hypothesize that pressure measurements
obtained selectively at this specific interval of the cardiac cycle
would allow a new pressure-derived index of stenosis severity
that does not require pharmacologic vasodilation; we term this
the instantaneous wave-free ratio (iFR). In the second part of
the study, this hypothesis was tested in a larger population by
comparing iFR and FFR measurements.
This document provides guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in adult patients. It summarizes the normal physiology of the HPA axis and adrenal response to stress. Regarding diagnosis, it finds low quality evidence and does not recommend the ACTH stimulation test or random cortisol alone. It suggests against using free cortisol levels and salivary cortisol levels over total serum cortisol. It conditionally recommends the high-dose over low-dose ACTH test for diagnosis due to ease of use and safety.
Pirfenidona na Fibrose Pulmonar IdiopaticaFlávia Salame
Pirfenidone reduced the decline in lung function in patients with idiopathic pulmonary fibrosis in one of two phase 3 clinical trials. In study 004, pirfenidone significantly reduced the decline in forced vital capacity at week 72 compared to placebo, but no significant difference was found between pirfenidone and placebo in study 006. Overall, pirfenidone showed a favorable benefit-risk profile and represents an appropriate treatment option for idiopathic pulmonary fibrosis.
The document provides an overview of US income tax fundamentals, including:
1) Income taxes raise revenue and are used as social and economic policy tools;
2) Individuals file forms like 1040EZ, 1040A, or 1040 depending on filing status and income level;
3) Corporations and partnerships differ in that corporations pay corporate income tax while partnerships "pass through" items of income/loss to partners.
The document discusses mobile learning (mLearning) using mobile devices to deliver interactive multimedia instruction. It outlines a project by researchers at Arizona State University to evaluate the impact of interactive tutoring and game-based environments on learning and engagement using mobile platforms. The document considers pros and cons of mLearning, compares it to eLearning, and proposes using scenarios and sensors in mobile devices to enhance learning experiences. The overall goal is to provide implications for developing effective mobile instruction.
Samraksha is a rural development organization in Karnataka, India that has worked for 17 years on HIV prevention and care programs. They operate in districts with high poverty, low literacy, and poor health access. Their key challenge is that the scale and speed of the HIV epidemic is greater than the response. Their key strategy is to release social capital by bringing people together through community conversations and activities to discuss issues, share experiences, and facilitate learning. This leads to community-led action and innovation like creating support systems for those affected by HIV, increasing open discussion of sexuality and HIV, and using art, dance, and other media to address stigma and spread awareness. Samraksha's experience shows that recognizing everyone's unique insights and promoting
Early goal-directed therapy in severe sepsis and septic shock: ProCESS, ARISE...Moh'd sharshir
1) This study compared early goal-directed therapy (EGDT) to usual care in patients with septic shock. EGDT aimed to optimize tissue oxygen delivery through monitoring of physiological targets like central venous pressure and central venous oxygen saturation.
2) The study found no significant difference in 90-day mortality between the EGDT and usual care groups. Patients in the EGDT group received more intravenous fluids and vasopressors but this did not impact mortality outcomes.
3) The study concludes that EGDT did not decrease mortality in patients presenting with septic shock compared to usual resuscitation practices. The value of incorporating EGDT into international guidelines is questionable.
Transcatheter intraarterial infusion of rt pa forHans Garcia
This study evaluated the success and complication rates of using intraarterial recombinant tissue-type plasminogen activator (rt-PA) infusion to treat acute lower extremity artery and bypass graft occlusions in 74 limbs of 70 patients. Thrombolytic success, defined as 95% thrombolysis and return of blood flow, was achieved in 86% of cases. Major bleeding complications occurred in 47% of patients, including bleeding at vascular access sites in 22 patients and remote bleeding in 7 patients. Despite the significant bleeding complications, 30-day mortality was 1% and amputation rate was 6%, resulting in a favorable 30-day amputation-free survival rate of 93%.
Damage control resuscitation (DCR) evolved from the concept of damage control surgery. It involves early blood product transfusions using a 1:1:1 ratio of red blood cells, plasma, and platelets to address trauma-induced coagulopathy. It also focuses on immediately arresting hemorrhage, restoring blood volume, and correcting physiological abnormalities like hypothermia and acidosis. DCR can be applied anywhere to critically injured patients. Massive transfusion protocols that guide DCR have been shown to improve survival rates in patients with severe injuries and hemorrhage. While DCR leaves surgical repairs incomplete initially, it buys time to stabilize patients sufficiently to allow for definitive care later.
New class of therapeutic agents called soluble guanylate cyclase (sGC) stimulators.
Impairment of NO synthesis and signaling through the NO-sGC–cGMP pathway is involved in the pathogenesis of pulmonary hypertension.
Dual mode of action,
Directly stimulating sGC independently of NO, and
Increasing the sensitivity of sGC to NO.
vasorelaxation , antiproliferative and antifibrotic effects
Comparison of two fluid management strategies in acute lung injuryDang Thanh Tuan
A randomized clinical trial compared a conservative fluid management strategy to a liberal strategy in patients with acute lung injury. The conservative strategy aimed to decrease lung edema by restricting fluid intake and increasing urine output, while the liberal strategy allowed more fluid administration. The primary outcome was 60-day mortality, with secondary outcomes including lung function and organ failures. The conservative strategy improved lung function and shortened time on ventilation and in the ICU without increasing other organ failures, though it did not significantly impact mortality.
Early Goal-Directed Therapy in Septic Shockshivabirdi
Early goal directed therapy (EGDT) aims to balance oxygen delivery and demand through manipulating cardiac preload, afterload and contractility using measures like lactate, base deficit and ScvO2. A study of 263 patients with severe sepsis or septic shock found that those receiving EGDT in the emergency department for at least 6 hours had significantly lower in-hospital, 28-day and 60-day mortality compared to standard therapy. EGDT also resulted in fewer organ dysfunctions, less coagulation abnormalities and cardiovascular collapse.
This randomized controlled trial evaluated the cardiovascular safety of semaglutide, a glucagon-like peptide-1 analogue, in patients with type 2 diabetes at high risk of cardiovascular events. The trial involved 3297 patients who were randomized to receive either once-weekly subcutaneous semaglutide (0.5 mg or 1.0 mg) or placebo for 104 weeks. The primary outcome was the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. The trial found that semaglutide was noninferior to placebo for the primary cardiovascular outcome and was associated with a significantly lower rate of the primary outcome compared to placebo. Rates of retinopathy complications were higher but rates of new or worse
This meta-analysis reviewed 5 randomized controlled trials involving 4,303 patients to determine if early goal-directed therapy (EGDT) according to Surviving Sepsis Campaign guidelines improves mortality outcomes in patients with severe sepsis or septic shock. The studies showed no statistically significant difference in 28-day, 60-day, or 90-day mortality between patients who received EGDT and those who received usual care. Secondary outcomes like hospital length of stay and need for organ support also did not differ significantly between the two groups. While EGDT decreased mortality, the effect was not statistically significant.
PROSEVA trial - Prone position in severe ARDS.
Why did prone position improve outcome of ARDS while other measures aimed at improving oxygenation such as high PEEP, RM and HFO have failed to do so?
The Emerging Role of BIomarkers and Bio-Impedancedrucsamal
This document discusses methods for assessing hydration status in patients with acute heart failure. It reviews classical assessment methods like history, physical exam, imaging techniques, and isotopic tracers, which is the gold standard but impractical. It then focuses on emerging roles of biomarkers and bioimpedance analysis which provide a less invasive way to estimate total body water content and fluid overload. These novel methods show promise for diagnosing, risk-stratifying, and guiding treatment decisions for acute heart failure patients.
The document discusses definitions, recognition, and interventions for sepsis. It begins by defining sepsis, severe sepsis, and septic shock according to the American College of Chest Physicians and Society of Critical Care Medicine. It then provides diagnostic criteria for systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic shock. The document discusses early goal-directed therapy (EGDT) as proven to reduce mortality in severe sepsis/septic shock. It outlines the Surviving Sepsis Care Bundles that are meant to be completed within 3 and 6 hours. The document discusses several studies related to sepsis management including lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy and the findings that cardiac filling pressures are
This document summarizes two studies on percutaneous left ventricular assist devices (LVADs) and coronary artery fistulas.
The first study investigated the ability of a percutaneous LVAD to deliver blood to the systemic circulation during cardiac arrest in pigs. The LVAD maintained blood flow and preferentially perfused vital organs like the brain. Intensified fluid loading further improved LVAD performance.
The second study evaluated the microvascular effects of ultrasound contrast (Definity) in hamsters with conditions like ischemia-reperfusion, diabetes, and sepsis. Inflammatory responses were higher in diabetes with ischemia and sepsis groups, independent of contrast use. Contrast did not alter hemodynamics or reology.
Understanding Antibiotics in Critically Ill Surgical PatientsAllison Boyd
1) The document discusses antibiotic stewardship principles, pharmacokinetic and pharmacodynamic changes in trauma and burn patients, and treatment recommendations for pneumonia and other infections in critically ill surgical patients.
2) It provides an overview of augmented renal clearance in trauma patients, inflammatory responses in burn patients, and how these physiologic changes can impact antibiotic dosing.
3) Guidelines for empiric treatment of pneumonia, including community-acquired pneumonia, hospital-acquired pneumonia, and ventilator-associated pneumonia, are reviewed based on risk factors and timing of infection onset.
Pearls about NSAIDs and their usage in the managaement of chronic pain, considering safety profile of both selective cox-2 or non selective cox-2 inhibitors
Autologous mononuclear and mesenchymal stromal cells infusion in COPD patients: impact on pulmonary capacity and quality of life in a Phase I randomized clinical trial
Identification of wave free period in the cardiac cycleRamachandra Barik
In the first part of this study, we identified the existence
of a diastolic interval in which intracoronary resistance at
rest is equivalent to time-averaged resistance during FFR
measurements. We hypothesize that pressure measurements
obtained selectively at this specific interval of the cardiac cycle
would allow a new pressure-derived index of stenosis severity
that does not require pharmacologic vasodilation; we term this
the instantaneous wave-free ratio (iFR). In the second part of
the study, this hypothesis was tested in a larger population by
comparing iFR and FFR measurements.
This document provides guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in adult patients. It summarizes the normal physiology of the HPA axis and adrenal response to stress. Regarding diagnosis, it finds low quality evidence and does not recommend the ACTH stimulation test or random cortisol alone. It suggests against using free cortisol levels and salivary cortisol levels over total serum cortisol. It conditionally recommends the high-dose over low-dose ACTH test for diagnosis due to ease of use and safety.
Pirfenidona na Fibrose Pulmonar IdiopaticaFlávia Salame
Pirfenidone reduced the decline in lung function in patients with idiopathic pulmonary fibrosis in one of two phase 3 clinical trials. In study 004, pirfenidone significantly reduced the decline in forced vital capacity at week 72 compared to placebo, but no significant difference was found between pirfenidone and placebo in study 006. Overall, pirfenidone showed a favorable benefit-risk profile and represents an appropriate treatment option for idiopathic pulmonary fibrosis.
The document provides an overview of US income tax fundamentals, including:
1) Income taxes raise revenue and are used as social and economic policy tools;
2) Individuals file forms like 1040EZ, 1040A, or 1040 depending on filing status and income level;
3) Corporations and partnerships differ in that corporations pay corporate income tax while partnerships "pass through" items of income/loss to partners.
The document discusses mobile learning (mLearning) using mobile devices to deliver interactive multimedia instruction. It outlines a project by researchers at Arizona State University to evaluate the impact of interactive tutoring and game-based environments on learning and engagement using mobile platforms. The document considers pros and cons of mLearning, compares it to eLearning, and proposes using scenarios and sensors in mobile devices to enhance learning experiences. The overall goal is to provide implications for developing effective mobile instruction.
Samraksha is a rural development organization in Karnataka, India that has worked for 17 years on HIV prevention and care programs. They operate in districts with high poverty, low literacy, and poor health access. Their key challenge is that the scale and speed of the HIV epidemic is greater than the response. Their key strategy is to release social capital by bringing people together through community conversations and activities to discuss issues, share experiences, and facilitate learning. This leads to community-led action and innovation like creating support systems for those affected by HIV, increasing open discussion of sexuality and HIV, and using art, dance, and other media to address stigma and spread awareness. Samraksha's experience shows that recognizing everyone's unique insights and promoting
The document provides an overview of programming with the iPhone SDK, describing the iPhone's features and limitations, the components of the SDK including Xcode, Interface Builder and frameworks, and how to develop applications using Objective-C including defining classes, methods, properties and protocols. It also includes examples of creating a simple Fraction class to demonstrate Objective-C concepts.
This document contains lecture slides for CSE340 - Principles of Programming Languages. It discusses parsing techniques, including error recovery, FIRST and FOLLOW sets, and prediction rules. It provides examples of calculating FIRST and FOLLOW sets for context-free grammars. It also discusses how FIRST and FOLLOW sets are used to implement predictive parsing and ensure predictions are unambiguous.
The document discusses semantic analysis for programming languages. It covers 6 parts of semantic analysis: declaration and unicity, type matching, array indexes, conditions, return types, and parameters. Conditions are reviewed to ensure expressions return a boolean value. The document provides an example of checking conditions in an if statement. It also outlines an assignment to implement semantic analysis and review conditions by checking the type returned from the stack is boolean.
Rotary International's theme for 2009-2010 is "The Future of Rotary is in Your Hands." The Rotary Club of Makati San Lorenzo held several planning meetings and events to kick off the new Rotary year under President Jing Sarao, including crafting the year-long plan, team visits for validation, joint meetings with other local clubs, and a handover ceremony from outgoing President Chacha Camacho. Past District Governor Jimmy Cura was the guest speaker at the inaugural meeting to share insights on serving the Rotary spirit for the year.
Lowering barriers to publishing biological data on the webBrad Chapman
Short 10 minute talk encouraging bioinformatics programmers to organize and reuse code targeted at making data easily available on the web. Current open source technologies are combined into a higher level framework. An example implementation using Google App Engine and existing bioinformatics libraries is presented.
The Rotary International theme for 2009-2010 focused on strengthening communities through service. The Rotary Club of Makati San Lorenzo had a busy week starting with a job training program called "Gunting Para sa Kabuhayan" to help people start careers in hair grooming. They also established a Rotary Community Corps in Antipolo to assist with ongoing service projects. Additionally, club members traveled to Batangas to support the "Kapit Bisig sa Ilog Pasig" project and interacted with community members living along the Pasig River.
The document discusses Ivan Illich's views on deschooling society and alternative models for learning. Illich criticized schools for being custodial institutions that assume learning must be taught through formal instruction. He argued that most learning occurs outside of school through friendship, reading, and life experiences. Illich proposed alternative "learning webs" where individuals could access networks, learning objects, skill exchanges, and educators to facilitate self-directed learning.
This tutorial will discuss key software architecture concepts allowing researchers and practitioners to move from software development as a one-ofa-kind endeavor to software development as a system of modules that can be widely used in highly adaptable ways. Participants will understand how the use of software architecture models avoids difficulty by providing robust and flexible systems, applies well-established methodologies, improves user experience and, warrants that the final product satisfies all the requirements (functional and non functional). The attendees will better understand how to apply software patterns as part of their software development methodology. They will engage in exercises that apply software patterns at architectural and design levels to create an Intelligent Tutor System (ITS) with an associated widespread use of components. And, understand how software architecture can improve ITS development to a point where one could be sure that the product would work, as planned, in uncontrolled and non-standardized environments and be able to be incrementally improved to be adapted with new technologies. The attendee will become familiar with the standard vocabularies of patterns in order to apply it as a way of shared communication inside the team and outside with the experts and consultants. This will improve attendees’ abilities to express and transfer knowledge that can enrich the development and improvement of systems.
Alice is an innovative 3D programming environment that makes it easy to create an animation for telling a story, playing an interactive game, or a video to share on the web. Alice is a freely available tool designed to be a student's first exposure to object-oriented programming. It allows people to learn fundamental programming concepts in the context of creating animated movies and simple video games. In Alice, 3-D objects (e.g., people, animals, and vehicles) populate a virtual world and students create a program to animate the objects. In Alice we drag and drop graphic tiles to create a program, where the instructions correspond to standard statements in a production oriented programming language, such as Java, C++, and C#. Alice allows us to immediately see how our animation programs run.
Rakuten aims to become the number one global internet company. To achieve this goal, Rakuten plans to run their entire business in English to create value between the internet and traditional businesses worldwide. Founded in 1997 in Japan, Rakuten has expanded over the years through mergers and acquisitions to offer a variety of e-commerce, travel, fintech, and other services globally.
Sony sells many consumer electronics products and has developed new technologies. However, to be successful in 2010 and beyond, Sony must cut costs, focus on developing user-centered products rather than just technologies, and address environmental issues like reducing CO2 emissions. Specifically, Sony plans to streamline its hardware businesses, provide new networked services, expand its customer base through improved marketing, and create more energy-efficient devices.
This document contains lecture slides for CSE340 - Principles of Programming Languages. It discusses intermediate code for while loops, if statements, and switch statements. It also covers a homework assignment to translate source code to intermediate code using a switch statement. The slides were presented by Javier Gonzalez-Sanchez and include code examples, notes on symbol tables, and a review of programming assignment 4.
Este documento presenta 3 diapositivas breves sobre el proceso de aprendizaje. La primera diapositiva indica que se está aprendiendo a hacer algo. La segunda continúa diciendo que el aprendizaje sigue. La tercera concluye expresando la esperanza de lograr lo que se está aprendiendo.
1) A study of over 6,000 COPD patients in Germany found that the most common symptom reported was dyspnea on exertion, and patients with higher COPD Assessment Test (CAT) scores reported more symptoms and comorbidities than those with lower CAT scores.
2) A separate study found that a stable elevated blood eosinophil percentage predicted shorter exacerbation durations in COPD patients treated with oral corticosteroids. Patients with eosinophil percentages over 2% had exacerbations that were on average 2 days shorter.
3) A third study found that one year of treatment with fluticasone propionate/salmeterol increased total bacterial loads in induced sputum samples of COP
cardiorenal syndrome and its characteristics and complications and causes.pptxArunDeva8
This study analyzed the risk factors and outcomes of acute cardiorenal syndrome (CRS-1) in 460 patients admitted with acute coronary syndrome or acute decompensated heart failure at a tertiary care center in South India. 34% of patients developed CRS-1, defined as acute kidney injury resulting from acute worsening of cardiac function. Risk factors for CRS-1 included diabetes, chronic kidney disease, lower ejection fraction, and higher levels of cardiac biomarkers. Patients with CRS-1 required more intensive care interventions and had higher in-hospital mortality of 20.2% compared to 7.8% in patients without CRS-1. Early detection and multidisciplinary management can help provide better outcomes for patients with
Coenzyme Q10 (CoQ10) plays a key role in mitochondrial ATP production and is an important antioxidant. Depleted levels of CoQ10 have been associated with various neurological and other disorders. CoQ10 supplementation has shown benefits for conditions such as Parkinson's disease, Huntington's disease, migraines, and Alzheimer's disease by improving energy production and reducing oxidative stress and inflammation in the brain. Doses of 360-2400 mg per day have been used effectively and safely in clinical studies to treat neurological conditions associated with CoQ10 deficiency.
REVIEW ARTICLE SEPTEMBER 2021 medical.pptxArunDeva8
This document summarizes the evolving use of biomarkers in the management of heart failure. It discusses how biomarkers such as BNP, NT-proBNP, cTn, ST2, and galectin-3 can be used to diagnose heart failure, establish disease prognosis and severity, and predict patient outcomes. Elevated levels of these biomarkers are associated with worse symptoms and higher mortality in heart failure patients. The document also presents a case study of an elderly male patient presenting with heart failure symptoms and discusses the clinical implications of his elevated BNP and cTnT biomarker levels.
This document contains summaries of several studies presented at the ACC24 conference around cardiovascular diseases like hypertension, angina, CAD, MI, AF, and HF. One study found that CSL112 infusions did not significantly reduce cardiovascular outcomes in AMI patients over 90 days compared to placebo. Another study found that a transcatheter inter-atrial shunt did not improve symptoms or prognosis in HF patients after 2 years regardless of LVEF. A third study found that Empagliflozin reduced HF hospitalization risk by 23-33% in post-MI patients but did not reduce all-cause mortality.
1) A double-blind clinical trial was conducted over 6 months to determine if a cysteine-rich protein supplement (IMN1207) had any positive or negative effects on clinical outcomes in lung cancer patients undergoing chemotherapy or radiotherapy compared to a casein protein supplement.
2) 35 lung cancer patients completed the study. Those receiving the cysteine-rich protein had a mean weight gain of 2.5% while those receiving casein lost 2.6% weight on average. Secondary outcomes like survival, muscle strength, and quality of life also improved more in the cysteine-rich protein group.
3) The cysteine-rich protein appeared to reverse weight loss and improve some measures of health more
IOSR Journal of Pharmacy (IOSRPHR), www.iosrphr.org, call for paper, research...iosrphr_editor
This study investigated the effects of oral clonidine premedication on hemodynamic changes during laparoscopic cholecystectomy. 100 patients were randomly assigned to receive either oral clonidine 150 micrograms or ranitidine 150 mg 90 minutes before surgery. Heart rate, blood pressure, and the need for antihypertensive treatment were significantly lower in the clonidine group during and after surgery. Postoperative nausea, vomiting, shivering, pain, and sedation were also reduced with clonidine premedication. The results suggest that oral clonidine can provide hemodynamic stability and reduce postoperative complications for patients undergoing laparoscopic cholecystectomy.
1) Recent studies have suggested that lower levels of weekly solute clearance through peritoneal dialysis are adequate, challenging previous guidelines recommending higher targets.
2) The ADEMEX and Hong Kong trials found no difference in patient survival between higher and lower dialysis dose groups, suggesting a minimum delivered weekly Kt/V of 1.7 may be sufficient.
3) The 2006 KDOQI guidelines established a minimum delivered weekly Kt/V target of 1.7 based on these studies, lower than the previous target of 2.1. Maintaining solute clearance above this minimum is recommended to optimize patient outcomes and longevity on peritoneal dialysis.
Evaluate of the Physical Performance of Patients Undergoing HemodialysisAhmed Alkhaqani
This study aimed to measure the physical performance of 62 patients undergoing hemodialysis using the Short Physical Performance Battery (SPPB) scale. The study found that the patients' physical performance was below predicted levels at baseline and deteriorated further over three assessments spaced four weeks apart. The results indicated poor physical performance in patients with chronic kidney disease undergoing hemodialysis. This was related to low physical activity levels in this patient population rather than demographic or clinical factors.
Аллопуринол и прогрессирование ХБП и кардиоваскулярные события. РКИ / Allopur...hivlifeinfo
Allopurinol and Progression of CKD and Cardiovascular Events- Long-term Follow-up of a Randomized Clinical Trial.Am J Kidney Dis. 2015 Apr
Background:Asymptomatic hyperuricemia increases renal and cardiovascular (CV) risk. We previously
conducted a 2-year, single-blind, randomized, controlled trial of allopurinol treatment that showed improved
estimated glomerular filtration rate and reduced CV risk.
Study Design:Post hoc analysis of a long-term follow-up after completion of the 2-year trial.
Setting & Participants:113 participants (57 in the allopurinol group and 56 in the control group) initially
followed up for 2 years and 107 participants followed up to 5 additional years.
Intervention: Continuation of allopurinol treatment, 100 mg/d, or standard treatment.
Outcome:Renal event (defined as starting dialysis therapy and/or doubling serum creatinine and/or$50%
decrease in estimated estimated glomerular filtration rate) and CV events (defined as myocardial infarction,
coronary revascularization or angina pectoris, congestive heart failure, cerebrovascular disease, and peripheral vascular disease).
Results:During initial follow-up, there were 2 renal and 7 CV events in the allopurinol group compared with
6 renal and 15 CV events in the control group. In the long-term follow-up period, 12 of 56 participants taking
allopurinol stopped treatment and 10 of 51 control participants received allopurinol. During long-term follow-up,
an additional 7 and 9 participants in the allopurinol group experienced a renal or CV event, respectively, and an
additional 18 and 8 participants in the control group experienced a renal or CV event, respectively. Thus,
during the initial and long-term follow-up (median, 84 months), 9 patients in the allopurinol group had a
renal event compared with 24 patients in the control group (HR, 0.32; 95% CI, 0.15-0.69; P50.004;
adjusted for age, sex, baseline kidney function, uric acid level, and renin-angiotensin-aldosterone system
blockers). Overall, 16 patients treated with allopurinol experienced CV events compared with 23 in the
control group (HR, 0.43; 95% CI, 0.21-0.88;P50.02; adjusted for age, sex, and baseline kidney function).
Limitations:Small sample size, single center, not double blind, post hoc follow-up and analysis.
Conclusions: Long-term treatment with allopurinol may slow the rate of progression of kidney disease and
reduce CV risk.
1) The study compared outcomes of treating septic shock using either conventional sepsis bundles guided by central venous pressure or improved sepsis bundles guided by pulse-indicated continuous cardiac output (PiCCO) measurements.
2) Patients receiving improved bundles guided by PiCCO had significantly lower organ failure scores, required less vasoactive drugs and fluid resuscitation, and had shorter durations of mechanical ventilation and ICU stays.
3) The improved bundles using PiCCO to guide fluid administration and cardiac function resulted in better clearance of lactate and reduced severity of septic shock compared to conventional bundles.
Implication of preoperative glycosylated hemoglobin level on short term outco...Dr.Debmalya Saha
ABSTRACT
Background: Diabetes mellitus is one of the significant risk factors for adverse outcomes after coronary artery bypass surgery. The glycosylated haemoglobin i.e. HbA1c is a reliable diagnostic test to know the long-term glycemic status. The objective of the study is to investigate the implication of preoperative HbA1c level on short term outcomes after coronary artery bypass grafting (CABG).
Method: Total 218 patients were studied, and the data were collected retrospectively. Patients are distributed into group 1 with HbA1c≤7 (good glycemic control) and group 2 with HbA1c>7 (poor glycemic control). The parameters studied for short term outcomes were revision due to bleeding, duration of mechanical ventilation, cerebrovascular accident (CVA), atrial fibrillation (AF), renal failure requiring dialysis, infective complications like sternal and leg wound infection, mediastinitis, pneumonia, urinary tract infection (UTI), sepsis; length of ICU stay and in-hospital mortality.
Result: In comparison to group 1, patients of group 2 showed statistically significant more morbidity in view of short-term outcomes in this study.
Conclusion: HbA1c>7 is associated with statistically significant adverse short-term outcomes after CABG.
Invasive coronary physiology to select patients for coronary revascularisation has become established in contemporary guidelines for the management of stable coronary artery disease. Compared to revascularisation based on angiography alone, the use of coronary physiology has been shown to improve clinical outcomes and cost efficiency. However, recent data from randomised controlled trials have cast doubt upon
the value of ischaemia testing to select patients for revascularisation. Importantly, 20-40% of patients have
persistence or recurrence of angina after angiographically successful percutaneous coronary intervention
(PCI). This state-of-the-art review is focused on the transitioning role of invasive coronary physiology from
its use as a dichotomous test for ischaemia with fixed cut-points, towards its utility for real-time guidance of PCI to optimise physiological results. We summarise the contemporary evidence base for ischaemia testing
in stable coronary artery disease, examine emerging indices which allow advanced physiological guidance
of PCI, and discuss the rationale and evidence base for post-PCI physiological assessments to assess the success of revascularisation.
Autologous steam cells infusion (ASCI) in COPD patients: impact on quality of...Dra. Mônica Lapa
Methods
Were recruited from the pulmonology ambulatory 20 grade 3 COPD (GOLD 2017) in a 12-month follow-up (Figure 1) and study was approved by the Institutional Review Board. Inclusion aged between 40 to 70 years undergoing optimized treatment for COPD with grade 2 or 3 that is, they were all using beta-2 long-action agonists associated with long-acting anticholinergic and inhaled corticosteroids; a forced expiratory volume in the first second (FEV1) of 30-50%, they have quitted tobacco use for at least six months and could be submitted to the pulmonary rehabilitation program. Exclusion: absence of emphysema on chest tomography; infection or history of infectious disease for less than 3 months; previous history of coronary artery disease; presence of pulmonary hypertension; use of home oxygen therapy; advanced hepatic or renal insufficiency; detection of immunosuppressive or infectious diseases; and presence of known neoplasms.
This document summarizes risk factors, recognition, management, and outcomes of perioperative acute kidney injury (AKI). It discusses how AKI increases surgical mortality and morbidity. Key points include:
- Perioperative AKI is common but often poorly recognized and managed.
- Identifying patients at high risk, such as those with chronic kidney disease or cardiac issues, allows clinicians to minimize renal insults.
- Management focuses on optimizing fluid status, blood pressure, treating sepsis, and removing nephrotoxic drugs when possible.
- Even mild AKI can have long-term effects, so early recognition and treatment are important.
Does Serum Lactate and Central Venous Saturation Predict Perioperative Outcom...crimsonpublishersOJCHD
Off-pump coronary artery bypass grafting (OP-CABG) surgery without the use of cardiopulmonary bypass (CPB) has come into practice for surgical treatment of Coronary artery disease (CAD) to reduce the post-operative systemic inflammatory response and post-operative morbidity. However, manipulation of the beating heart during OP-CABG surgery brings significant fluctuations in the patients haemodynamics leading to occult hypo-perfusion and 'Global tissue hypoxia' (GTH) -a decrease in oxygen utilization associated with anaerobic metabolism.
2023 Definitions, phenotypes, and subphenotypes in AKI.pdfJesusPlanelles
The document discusses the need to reclassify acute kidney injury (AKI) to facilitate more targeted and individualized treatment approaches.
Current AKI definitions focus only on functional changes like rises in creatinine, which detect injury too late for early intervention. The document proposes reclassifying AKI based on causal phenotype and subphenotypes defined by biomarkers that reveal specific injury pathways.
Precisely defining AKI phenotypes by cause, such as ischemia or nephrotoxins, and subphenotypes by activated pathophysiological mechanisms, could help triage patients to tailored therapies in a precision medicine approach, rather than just providing supportive care for the broad AKI syndrome.
1) The study examined whether enhanced external counterpulsation (EECP) treatment reduces hospitalization rates and healthcare costs in patients with refractory angina. EECP involves applying pressure to the legs during the cardiac cycle to improve blood flow.
2) Data on 1015 refractory angina patients showed hospitalization rates fell from 55.2% pre-EECP to 24.4% 6-12 months post-EECP. Hospitalizations per patient fell from 1.7 to 1.4.
3) The estimated annual savings per patient from reduced hospitalizations was $17,074 after subtracting the average $4,880 EECP cost, indicating EECP is cost-effective for reducing healthcare
The document discusses francophone seances for the 2014 JIFA conference. It lists the names N. Gaye, XL Modedero, V. Arfi, and M. Bouayed, suggesting they are presenters or participants. In 3 sentences or less, the summary provides a high-level overview of the topic and purpose while maintaining essential information from the original text.
This document summarizes several studies investigating the relationship between smoking and venous thromboembolism (VTE) risk. The studies found:
1) Current smoking was associated with a higher risk of VTE compared to never smokers, with a positive dose-response relationship. Former smokers had the same risk as never smokers.
2) Heavier smokers (>20 pack-years) had higher risks of total and provoked VTE compared to never smokers. The risk of provoked VTE increased with more pack-years of smoking.
3) The modestly increased risks of VTE in current or former women smokers were attenuated after adjusting for smoking-related diseases and decreased physical activity, suggesting an indirect relationship between smoking
1. 007-014 Belcaro 27/01/10 10:29 Page 7
ARTÈRES 7
Supportive Treatment with CoenzymeQ10
in Heart Failure: The Irvine3 Labs Study on
Heart Failure in Vascular Patients
G. BELCARO MD, PhD, M. R. CESARONE MD, A. LEDDA MD, U. CORNELLI MD, M. DUGALL BA,
S. STUARD MD, E. IPPOLITO MD, M. G. GROSSI, I. RUFFINI MD
IRVINE3 CARDIOVASCULAR LABS – DEPT. BIOMEDICAL SCIENCES – CHIETI-PESCARA UNIVERSITY
SUPPORTED BY THE MINISTRY OF UNIVERSITY, SCIENCE & TECHNOLOGY (MURST) AND ISVI
(Italian Society for Vascular Investigations)
Corresponding Author: Gianni Belcaro, MD, PhD, C.So Umberto I, 12, San Valentino Vascular Screening Center,
65020 San Valentino, PE, ITALY – cardres@abol.it
Conflict of Interest: There was no conflict of interest. fraction improved (from 25.7%; range 17-40 to 29.2%; 18-
None of the authors were connected in any way with the 44*; p<0.05; variation equivalent to a 4.5% increase). The
product quoted in this article. CoQ10 was not supplied by a improvement in walking distance was 45.7% of the initial
specific company but acquired by commercial producers not value (p<0.05); the Karnofski scale value improved from an
related in any way to the study. initial median of 57.7 to 63.2 (p<0.05); (5, 5% increase).
Conclusion. CoQ10 supplement improves both clinical
Abstract and physiological parameters in HF. Low CoQ10 values may
increase mortality in HF, but supplementation may be use-
The aim of this registry was the evaluation of the clini- ful to improve clinical parameters and, possibly, outcome
cal value of CoQ10 in heart failure (HF) during a 12-week and mortality.
observation period. Patients with stable congestive HF
(NYHA class II-III), limited exercise capacity (Karnofsky scale Key Words: Heart failure, ejection fraction, NYHA
value between 50 and 70) and reduction in ejection fraction classification, ventricular function, cardiovascular
(< 41%) were included. A clinical and physiological evalua- disease, Coenzyme Q10
tion (exercise capacity, ejection fraction) was used. The
study focused on vascular patients with past symptoms. A
single oral dose of CoQ10 (100 mg/day) was used. 107 Résumé
patients (out of 120 included) completed at least 12 weeks.
Mean age was 62.4 ± 6.9. No side effects due to CoQ10 Le but de cet article était l’évaluation de la valeur cli-
were recorded. Dropouts were due to poor compliance or nique de CoQ10 dans l’insuffisance cardiaque pendant une
logistics; 2 patients had hospital admission for emergency; période d’observation de 12 semaines. Les patients avec une
3 patients died for causes related to HF. Other cardiovascu- insuffisance cardiaque (IC) congestive stable (classe II-III
lar disease was associated in all patients. NYHA), avec diminution des capacités physiques (échelle de
Results. There was a mild decrease in systolic pressures Karnofsky entre 50 et 70) et une réduction de la fraction
(p<0.05) and a decrease in heart and respiratory rate d’éjection (< 41%) étaient inclus. Une évaluation clinique et
(p<0.05). The average weight of patients decreased physiologique (capacité à l’exercice, fraction d’éjection)
(p<0.05); (6.24% less than the initial value). Signs/symp- était utilisée. L’étude s’est focalisée sur les patients vascu-
toms improved (improvement of at least 3 symptoms was laires présentant des symptômes anciens. Une seule dose
observed in 63% of patients). At 12 weeks we had to real- orale de CoQ10 (100 mg/jour) était prescrite. 107 patients
locate NYHA classes: 6 out of 44 patients passed from class (parmi les 120 inclus) ont complété l’étude pendant au
II to I, and 9 out of 63 passed from class III to II. In total, moins 12 semaines. L’âge moyen était de 62.4 ± 6.9. Aucun
14.01% of patients passed to the lower class. There was a effet secondaire du CoQ10 n’a été noté. Les sorties d’étude
significant improvement in “target measurements”: ejection étaient dues à une compliance insuffisante ou à des pro-
ANGÉIOLOGIE, 2010, VOL. 62, N° 1
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8 ARTÈRES
blèmes logistiques ; 2 patients ont été hospitalisés en mortality in HF. CoQ10 deficiency may alter the long-term
urgence ; 3 patients sont décédés de cause liée à l’IC. Une prognosis of HF. This study (3) suggested that there is a
autre pathologie cardiovasculaire était associée chez tous rationale for interventional studies using CoQ10 as a sup-
les patients. plement in most patients with HF. Other studies (4-8) also
Resultats. On a noté une légère diminution des pres- indicate the important potential role of CoQ10 in patients
sions systoliques (p<0.05) et une diminution des fré- with heart failure.
quences cardiaques et respiratoires (p<0.05). Le poids CoQ10 is considered a key, essential element within
moyen des patients a diminué (p<0.05); (6.24% de moins the mitochondrial chain as it contributes to the produc-
que le poids initial). Les signes et symptômes se sont amé- tion of ATP (3,9). CoQ10, present in myocardial biopsies
liorés (une amélioration d’au moins 3 symptômes a été from patients, tends to be decreased in patients with HF
observée chez 63% des patients). A 12 semaines, nous (10). Its correct levels may contribute to the modulation
avons reclassé les patients selon la classification NYHA : 6 of the most effective performance of normal hearts and
patients sur 44 sont passés de la classe II à la classe I, et particularly of failing hearts.
9 sur 63 de la classe III à II. Au total, 14,01% des patients Several studies show the effects of CoQ10 supple-
sont repassés dans une classe inférieure. Il y a une amé- mentation to be the “best cardiological therapy” in
lioration significative des « objectifs cibles »: la fraction improving HF, particularly when CoQ10 levels are low
d’éjection a été augmentée de 25.7% (écart type : 17-40) (2-3,11-16), i.e., in patients using statins. It has been
à 29.2% (écart-type : 18-44*); (p<0.05); (variation équi- shown that both low levels of total cholesterol and
valente à une augmentation de 4.5%). L’amélioration du CoQ10 (linked to the same metabolic pathways) contri-
périmètre de marche était de 45.7% par rapport aux bute to higher mortality in HF patients and that higher
valeurs initiales (p<0.05); l’échelle de Karnofski était amé- total cholesterol levels (and CoQ10 levels) are associa-
liorée d’une moyenne initiale de 57.7 à 63.2 (p<0.05); (5, ted to a decreased mortality in these patients.
5% d’augmentation). In prospective studies it has been shown that after
Conclusion. La supplémentation en CoQ10 améliore à la administration of CoQ10 for 2-4 weeks there is an
fois les paramètres cliniques et physiologiques dans l’IC. Des increase in ejection fraction and workload capacity. This
valeurs basses en CoQ10 peuvent augmenter la mortalité generally results in an improvement in NYHA functional
dans l’IC, mais la supplémentation pourrait être utile pour class (17) and in a significantly lower mortality rate in
améliorer les paramètres cliniques et, vraisemblablement, le long-term studies (11,14) when CoQ10 is added to the
pronostic et la mortalité. most updated therapy for HF.
The aim of this prospective study – still in progress –
Mots-Clés : Insuffisance cardiaque, fraction was the evaluation of the clinical value of CoQ10 sup-
d’éjection, maladie d’éjection, maladie cardiovas- plements in a 12-week observation period. We included
culaire, coenzyme Q10 in the registry (according to the protocol of the Italian
Multicenter Study) (2) subjects with stable (within the
*** previous 6 months) congestive HF (NYHA class II-III),
limited exercise capacity, a Karnofsky scale (18-21)
Introduction value ranging between 50 and 70, and a stable reduc-
tion in ejection fraction < 40%.
In patients with heart failure (HF), the reduced effi- According to the NYHA classification, Class II (mild)
ciency of the myocardium is generally associated with a includes patients with slight limitation of physical acti-
reduced supply of calcium ions to contractile muscular vity. They are comfortable at rest, but ordinary physical
proteins. The impairment of energy-dependent calcium activity results in fatigue, palpitation, or dyspnea.
ion transport is a very early key element that has an Patients in Class III (moderate) show a marked limitation
important role in the progression of signs and symptoms of physical activity. They are comfortable at rest, but
linked to HF (1, 2). less than ordinary activity causes fatigue, palpitation, or
An important Italian multicenter study that included a dyspnea.
large number (2664) of patients with HF has indicated that The registry protocol was initially comparable to the
signs and symptoms significantly and clinically improve, as study protocol of the Italian Multicenter study on the
well as the quality of life (2), with the use of coenzyme Q10 Safety and Efficacy of CoQ10 in HF (Baggio E et al, (1)).
(CoQ10) as an adjunctive treatment for HF for only 3 Even with some modifications in our study, this protocol
months. A recent study from Molyneux (3) has shown that offers comparative data specific to our population. To
plasma CoQ10 concentrations are independent predictors of this study protocol we added a more functional and
ANGÉIOLOGIE, 2010, VOL. 62, N° 1
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ARTÈRES 9
Table 1. Inclusion criteria and main measurements.
physiological evaluation (exercise capacity and varia-
tions in ejection fraction). Also this specific study was Exclusion: Alvular disease (hemodynamically
mainly focused on vascular/angiological patients with significant)
symptomatic (in the past) vascular problems. Recent, acute MI (previous 3 months),
Angina
Congenital heart disease
Patients and methods Severe hypertension
Diabetes and metabolic diseases requiring
Inclusion and exclusion criteria are shown in Table 1. treatment
Essential for inclusion was a constant treatment in the pre- Surgery for cardiac revascularisation
vious 3 months and stability in the NYHA class in the pre- (within previous 3 months)
vious 6 months. TIAs or strokes within the previous 6
months
Adverse reactions to CoQ10 or other comparable com- Severe (requiring treatment) neurological,
pounds forced exclusion. We also excluded subjects using renal, hepatic or metabolic disease
statins or other lipid-lowering agents, focusing, in the case NYHA functional class I and IV
of high cholesterol levels (>220), on a specific diet, as sta-
Inclusion: Heart failure diagnosed and stable for at
tins may have an important effect on CoQ10. least 6 months before
Inclusion. Informed consent
Clinical evaluation
MAIN TARGET MEASUREMENTS:
A: Ejection Fraction <41%
A 2 to 7 point scale for signs and symptoms (Table 2) was B: Walking Distance <200 m
used to evaluate the clinical picture according to the IMS C: Karnofsky Scale (between 50 and
(2). Cyanosis was scaled between 0 and 3; edema 0-3; pul- 70%)
monary crepitations/rales 0-4; enlargement of the liver 0-3;
jugular reflux 0-2; dyspnea 0-6; palpitations 0-3, insomnia Table 2. Assessment of signs and symptoms. The 2 to 7
0-3; sweating 0-1; subjective arrhythmia 0-3; vertigo 0-3; point scale according to Baggio E (2) used for assessment
and nocturia 0-3. of signs/symptoms in the IMS.
Patients SIGN/SYMPTOM SCORE
Cyanosis 0-3
Edema 0-3
A group of 234 patients was screened; 107 were inclu-
Pulmonary rales 0-4
ded mainly due to their stability and possible compliance. Enlargement of liver 0-3
The therapy used for these patients was considered to be Jugular reflux 0-2
the “best treatment” according to the AHA guidelines (15) Dyspnea 0-6
as given by their cardiologists. There was no interference on Palpitations 0-3
the treatment prescribed by the cardiologists. Insomnia 0-3
Sweating 0-1
Subjective Arrhythmia 0-3
Evaluation of the Left Ventricular Function Vertigo 0-3
Nocturia (voiding at night) 0-3
A Terason, Prosound ultrasound system, (Aloka, Japan)
with a 4V2 A probe was used. Left ventricular volume was
calculated according to the Simpson rule following the gui- km/h for 3 minutes or less, depending on patients’ condi-
delines issued by the American Society of Echocardiography. tions and signs/symptoms; the total distance was the mea-
The analysis of the left ventricular volumes includes measu- surement in meters of the total distance the patient was
rements of end-diastolic and end-systolic left ventricular able to walk. No patient was actually able to complete the
volumes. Calculation of the ejection fraction (EF%) was 3-minute test.
made from the apical projection (4-chambers). An EF < 40%
(23-26) was part of the inclusion criteria for all patients. Main “Target” Measurements
Exercise treadmill (27) The main physiological and clinical targets (in addition to
the observations replicating the IMS) were the evaluation of:
The test was performed according to our vascular labo- A. Ejection Fraction: measured as percent of left ventri-
ratory standards. A treadmill was used at the speed of 3 cular volume (expressed as median and range).
ANGÉIOLOGIE, 2010, VOL. 62, N° 1
4. 007-014 Belcaro 27/01/10 10:29 Page 10
10 ARTÈRES
Table 3: the Karnofsky Performance Scale Index classifies
B. Walking Distance: measured in meters (mean and SD). patients according to their functional impairment. The
The patients were able to walk. scale is used to compare effectiveness of different thera-
C. Karnofsyi Scale (Table 3). Patients were unable to pies and to assess the prognosis in individual patients. The
work but were able to live at home and care for most lower the Karnofsky score, the less chance for survival.
personal needs. Varying amounts of assistance were
needed. Subjects with scores (%) between 50 and 70
KARNOFSKY PERFORMANCE STATUS SCALE DEFINI-
were included. Patients with a score of 70 were able TIONS RATING (%) CRITERIA
to care for themselves but were unable to carry on
normal activity or to do active work. Patients with a Able to carry on normal activity and to work; no spe-
cial care needed.
score of 60 required occasional assistance but were
able to care for most of their personal needs. Patients 100 Normal, no complaints; no evidence of disease.
90 Able to carry on normal activity; minor signs or
with a score of 50 required considerable assistance symptoms of disease.
and frequent medical care. All measurements were 80 Normal activity with effort; some signs or
expressed in percentage (median and range). symptoms of disease.
Unable to work; able to live at home and care for
Daily dosage of Pycno-CoQ10 most personal needs; varying amount of assistance
needed.
The daily dosage (according to the Italian Multicenter 70 Cares for self; unable to carry on normal acti-
Study, IMS) was initially established at 100 mg of oral vity or to do active work.
CoQ10. Overweight subjects (>95 Kg) and smaller or 60 Requires occasional assistance, but is able to
underweight subjects (<50 Kg) were excluded to keep the care for most of his personal needs.
doses geared to a standard population sample. Non-bran- 50 Requires considerable assistance and frequent
medical care.
ded, commercially available 100mg capsules were used
and given in unmarked boxes of 150 capsules. Interactions Unable to care for self; requires equivalent of institu-
tional or hospital care; disease may be progressing
with other drugs or products active on the gastrointesti- rapidly.
nal tract and on the absorption of CoQ10 were carefully
40 Disabled; requires special care and assistance.
excluded. One single daily dose was used between 8 and 30 Severely disabled; hospital admission is indica-
10 am. ted although death not imminent.
20 Very sick; hospital admission necessary; active
Statistical Anaylsis supportive treatment necessary.
10 Moribund; fatal processes progressing rapidly.
Statistics were analyzed with a Sigma-Plot program. The 0 Dead
variability of testing was considered: a variation in ejection
fraction <4% was considered normal in both intra-indivi- Differences in demographic parameter (in patients survi-
dual and inter-individual measurements. A variation of ving the 3-month study period) were compared using the
<5% of treadmill distance was considered within normal Mann-Whitney rank sum U-test and chi-square test
intra-individual and inter-individual measurements when (Pearson chi-square-2 sided asymptotic significance) accor-
repeating the test. Therefore, to be clinically significant an ding to Molineux (3).
improvement in ejection fraction and in treadmill distance
>4% was considered the cut-off point necessary to define Informed Consent
“improvement” in time that may be attributed to treatment
or management. Descriptive statistics with median and Oral, witnessed consent was obtained by all incuded
range (percentages) or mean with standard deviation and subjects.
range were used for continuous or parametric variables
while non-continuous variables (i.e. signs/symptoms) were Results
expressed as percentage and frequency.
Analysis of the variations between inclusion and after- Details of patients are shown in table 4: 107 patients
treatment values was made with the t test (for normally out of 120 completed the follow up (at least 12 weeks).
distributed parameters) or using the Wilkoxon signed-rank Their mean age was 62.4 ±6.9 (range 45-70); the mean
test for scores (signs/symptoms); chi-squared and Mann duration of heart failure before inclusion was of 32.2 ±
Whitney U-test were used for frequency data and percen- 4.3 months.
tages. P< 0.05 was considered as the significance level. No side effects due to CoQ10 treatment were recorded.
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Table 4: Details of patients completing the study. Table 5: Results.
Number Drop outs Deaths BLOOD PRESSURE At inclusion After treatment
No. patients Total 107 Supine Systolic 144.3;12.4 141.1;7.8*
Class II 44 (41.12%) 7 1 Diastolic 81.2;7.9 80.1;6.6
Class III 63 (58.8%) 6 2 Sitting Systolic 146.3;11.1 142.2;8.4*
Diastolic 82.1;6.8 80.2;7.1*
Mean age 62.4;6.9 range 45-70
Heart rate 79.2;9.2 76.1;7.7*
Mean duration of heart failure 32.2;4.3 months
Respiratory rate 22.8;4.1 21.1;4.5*
Most used standard treatments at inclusion:
Serum Na mmol/l 142.3;11.1 141.5;10.2
TREATMENTS (% of patients) Serum K mmol/l 4.19;0.6 4.2;0.5
Digitalis 36.1
Diuretics 57.2
Table 6: Trial results: variation in signs and symptoms.
ACE-inhibitors 33.5
Ca Antagonists 11.3 Present % IMPROVED AT
Inotropic agents 12.1 At inclusion LEAST 1 POINT
Nitrates 7.9 AFTER TREATMENT
Others 14.3
SIGNS
- Cyanosis 26% 77.6
There was a total of 13 drop-outs (7 in NYHA class II and - Edema 78% 81
6 in class III): 4 were due to poor compliance, 7 were lost to - Pulmonary
follow up for logistical reasons, and 2 had hospital admis- crepitations 75% 79
- Liver enlargement 57% 52
sion for severe emergency care followed by surgery (and
- Jugular reflux 33% 76
therefore were considered excluded). Three patients died for
causes related to heart failure (one was in NYHA II and 2 in SYMPTOMS
NYHA III). - Dyspnea 93% 66
- Palpitations 83% 79
Other cardiovascular disease was associated with HF in
- Sweating 45% 72
all patients: 45% of these patients had stenotic carotid - Subjective
(22% symptomatic in the past) and/or femoral atherioscle- arrhytmia 46% 76
rotic plaques (symptomatic in the past in 38% patients) - Insomnia or
with aortic dilatations (23% of patients) and real aneu- sleep disturbances 61% 71
rysms (12% of patients) with maximum diameter >4 cm. In - Dizziness 58% 78
35% of the subjects symptomatic peripheral arterial disease - Nocturia 62% 51
was associated with intermittent claudication. In most
patients the vascular problems were multiple. centage of patients with specific signs/symptoms at inclu-
The most used treatments at inclusion are shown in sion and at 12 weeks is also indicated in table 6.
Table 4. These treatments were maintained in most patients At 12 weeks we had to reallocate NYHA classes because
(89%) during the follow up period, as one of the aims of the 6 out of 44 patients passed from class II to I, and 9 out of
study was to evaluate stable patients. One-drug treatment 63 patients passed to class II from the initial class III. In
was used in only 6% of patients, but 3 (or more) drugs were total 15 patients out of 107 (14.01%) passed to the lower
used for treatment in 79% of these patients. class.
Variations in blood pressure and heart rate are shown in No progression (no increase in NYHA class) was observed
Table 5. There was a mild decrease in both systolic pressures in these patients.
and in the sitting diastolic pressure (p<0.05) and a decrease No significant alterations in blood tests were seen in 3
in heart rate and respiratory rate (p<0.05). Plasma Na and months.
K did not have significant changes.
The average weight of patients decreased (p<0.05) from Main Target Measurements (table 7)
an average value of 86.5;5 Kg to 81.1;4.4 (6.24% less than
the initial value). There was a significant improvement in the three “target
All clinical signs and symptoms improved at least 1 point measurements” as the ejection fraction improved from the
in most patients (Table 6). Improvement of at least 3 symp- initial median value of 24.7% (range 17-40) to 29.2% (18-
toms/signs was observed in 63% of all patients. The per- 44)* (p<0.05; variation equivalent to a 4.5% increase). The
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Table 7: Main target measurements CoQ10 in the myocardium of patients with HF is
INCLUSION 12 WEEKS
generally low (3). The association between low levels of
CoQ10 and lowered survival rates has promoted a num-
A: EJECTION FRACTION 24.7% 29.2% ber of trials to study CoQ10 in HF (12, 31-34). With these
(%) (range 17-40) (18-44)* studies it was possible to show improvements in clinical
B: WALKING DISTANCE parameters as well as in physiological measurements
(m) 105 153 such as stroke volume, ejection fraction, and cardiac
C: KARNOFSKY SCALE output after supplementation with CoQ10 for various
(%) 57.7(40-69) 63.2 (49-74)* periods (31-35). With an improvement in technology, a
better evaluation of the left ventricular function in HF
* p<0.05
(36-37) will probably allow a more precise quantitative
measurement of ventricular function in association with
improvement in walking distance was 45.7% of the initial treatment.
value (p<0.05), and the Karnofsky scale value improved The connection between CoQ10 decreased levels and
from an initial median of 57.7(range 40-69) to 63.2 (range “statin-related myopathy,” which may be associated to
49-74) (p<0.05; equivalent to a 5,5% increase). some kinds of HF, needs a different investigational
approach and a much larger study (38).
Conclusions The role of statins in accelerating or even causing HF is
often controversial and still in evaluation. It may be particu-
In this study blood pressure and heart rate decreased, larly important considering the diffusion of statin treatment.
confirming results from previous studies (28). An important At the moment, an international multicenter, randomi-
reduction in peripheral vascular resistance is possibly due to zed, double-blind trial (Q-SYMBIO) is focusing on signs and
the inhibition by CoQ10 of the sympathetic overactivity symptoms, bloodmarkers (B-type natriuretic peptide) and
present early in heart failure in most patients (29,30). long-term outcomes (35) in HF patients.
These results suggest that CoQ10 supplements improve
HF in most patients in classes II and III. Patients in NYHA Conclusion
class II appear to show better results with CoQ10.
The improvement was present in more than 85% of all Low CoQ10 may be associated with HF or aggravate the
included patients. CoQ10 showed a good tolerability and no clinical situation. Low levels may also increase mortality
side effects were recorded. Results in our population sample rates in HF. According to this open preliminary study, sup-
are broadly comparable to the observations from the Italian plementation improves clinical and physiological parame-
Multicenter Study lead by Baggio, including 173 centers (2). ters and, possibly, outcome and mortality.
Also, results from this study repeat the results obtained by
Judy (11) and Langsjoen (14) and are comparable to the Acknowledgements
results recently obtained by Molyneux (3).
The bad tolerability of CoQ10 supplements is usually We are very grateful to Prof. A Barsotti (University of
transient or marginal and can be controlled either by redu- Genoa) former director of the school of Cardiology Chieti-
cing dosage or suspending treatment. Pescara University, and Prof. F Caciagli, Dept. Biomedical
The observed independent association between low Sciences, G D’Annunzio University), Deutsche Bank.
levels of CoQ10 and increased mortality due to HF is grea-
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