Hernando Gomez | University of Pittsburgh (original) (raw)
Papers by Hernando Gomez
Critical Care Medicine, 2020
Introduction/Hypothesis: We have previously demonstrated that shedding of the glycocalyx increase... more Introduction/Hypothesis: We have previously demonstrated that shedding of the glycocalyx increases platelet adhesion in the renal peritubular capillaries resulting in acute kidney injury (AKI) regardless of the severity of the inflammatory response. We now hypothesized that blockade of Pselectin, a key endothelial adhesion molecule involved in leukocyte and platelet adhesion, would decrease platelet adhesion after glycocalyx shedding, resulting in improved microvascular and organ function. Methods: C57BL/6 (n=5-6/group) mice were assigned to control (vehicle or sham), hyaluronidase (Hyal: 140 IU IA q8h for 24 hours) as a model of sterile glycocalyx denudation, cecal ligation and puncture (CLP) as a model of sepsis. All groups received anti-P-selectin (P-sel) antibody (2mg/kg IA at 12 and 24hrs following initial injury). Outcomes were measured at 24hrs: Glycocalyx shedding and systemic inflammation were assessed using plasma syndecan-1 (SDC-1) (pg/ml) and IL-6 (pg/ml), respectively. Platelet adhesion in renal peritubular capillaries (# of platelets adhered longer than 10s per 100μm of capillary) was quantified using multiphoton intravital microscopy. Serum creatinine (sCr) (mg/dl) was used to evaluate renal injury. Results: Hyal and CLP resulted in increased SDC-1 levels (Cntl 421.1±87.04 vs Hyal 2134.2±530.4 p=0.02; Sham 535.7±146.1 vs CLP 4914±588.1; p<0.01), however, only CLP had an increase in IL-6 (Cntl 529.4±452.9 vs Hyal 353.8±89, p=0.43; Sham 508.7±258.7 vs CLP 7759±5528 p=0.03). Treatment with P-selectin following insult resulted in reduced platelet adhesion in the Hyal group and a trend in the CLP group (Hyal 2.47±2.12 vs Hyal+P-Sel 0.53±0.13 p=0.02; CLP 1.66±2.18 vs CLP+P-Sel 0.42±0.3 p=0.22) and decreased sCr levels in both groups (Hyal 1.48±0.82 vs Hyal+P-Sel 1.21±0.29 p=0.03; CLP 3.47±0.7 vs CLP+P-Sel 2.33±0.29 p=0.03). Conclusions: Glycocalyx shedding increases platelet adhesion, regardless of the severity of the systemic inflammatory response, resulting in microcirculatory dysfunction contributing to AKI. Blockade of P-selectin and platelets interaction results in decreased platelet adhesion and organ function improvement. These results suggest that platelet adhesion blockade constitutes a potential therapeutic target for microvascular dysfunction in sepsis induced AKI.
Circulation, Oct 28, 2008
Critical Care Medicine, Nov 9, 2020
Objective:To compare 5% albumin to 0.9% saline for large-volume resuscitation (LVR, > 60ml/Kg wit... more Objective:To compare 5% albumin to 0.9% saline for large-volume resuscitation (LVR, > 60ml/Kg within 24h), on mortality and development of acute kidney injury (AKI).Design:Retrospective cohort study.Setting:Patients admitted to intensive care units (ICUs) in 13 hospitals across Western Pennsylvania. We analyzed two independent cohorts, the High-Density Intensive Care (HiDenIC) databases: HiDenIC08 (July 2000 to October 2008, H08) and HiDenIC15 (October 2008 to December 2014, H15).Patients:Total of 18,629 critically ill patients requiring LVR.Interventions:5% albumin in addition to saline vs 0.9% saline.Measurements and Main Results:After excluding patients with AKI prior to LVR, 673/2,428 (27.7%) and 1,814/16,201 (11.2%) patients received 5% albumin in H08 and H15, respectively. Use of 5% albumin was associated with decreased 30-day mortality by multivariate regression in H08 (OR 0.65, 95% CI 0.49–0.85, p=0.002) and in H15 (0.52, 95% CI 0.44–0.62, p<0.0001), but was associated with increased AKI in H08 (OR 1.98, 95% CI 1.56–2.51, p<0.001) and in H15 (OR 1.75, 95% CI 1.58–1.95, p<0.001). However, 5% albumin was not associated with persistent AKI, and resulted in decreased MAKE at 30, 90 and 365 days. Propensity matched analysis confirmed similar associations with mortality and AKI.Conclusion:During LVR, 5% albumin was associated with reduced mortality and MAKE at 30, 90 and 365 days. However, a higher rate of AKI of any stage was observed that did not translate into persistent renal dysfunction.
Critical Care, Oct 18, 2017
All of medicine aspires to be precise, where a greater understanding of individual data will lead... more All of medicine aspires to be precise, where a greater understanding of individual data will lead to personalized treatment and improved outcomes. Prompted by specific examples in oncology, the field of critical care may be tempted to envision that complex, acute syndromes could bend to a similar reductionist philosophy-where single mutations could identify and target our critically ill patients for treatment. However, precision medicine faces many challenges in critical care. These include confusion about terminology, uncertainty about how to divide patients into discrete groups, the challenges of multi-morbidity, scale, and the need for timely interventions. This review addresses these challenges and provides a translational roadmap spanning preclinical work to identify putative treatment targets, novel designs for clinical trials, and the integration of the electronic health record to implement precision critical care for all.
Critical Care Medicine, Dec 16, 2021
Shock, Mar 1, 2016
Mitochondria are an essential part of the cellular infrastructure, being the primary site for hig... more Mitochondria are an essential part of the cellular infrastructure, being the primary site for high energy adenosine triphosphate (ATP) production through oxidative phosphorylation. Clearly, in severe systemic inflammatory states, like sepsis, cellular metabolism is usually altered and end organ dysfunction not only common but predictive of long term morbidity and mortality. Clearly, interest is mitochondrial function both as a target for intracellular injury and response to extrinsic stress have been a major focus of basic science and clinical research into the pathophysiology of acute illness. However, mitochondria have multiple metabolic and signaling functions that may be central in both the expression of sepsis and its ultimate outcome. In this review, the authors address five primary questions centered on the role of mitochondria in sepsis. This review should be used as both a summary source in placing mitochondrial physiology within the context of acute
JAMA, May 28, 2019
IMPORTANCE Sepsis is a heterogeneous syndrome. Identification of distinct clinical phenotypes may... more IMPORTANCE Sepsis is a heterogeneous syndrome. Identification of distinct clinical phenotypes may allow more precise therapy and improve care. OBJECTIVE To derive sepsis phenotypes from clinical data, determine their reproducibility and correlation with host-response biomarkers and clinical outcomes, and assess the potential causal relationship with results from randomized clinical trials (RCTs). DESIGN, SETTINGS, AND PARTICIPANTS Retrospective analysis of data sets using statistical, machine learning, and simulation tools. Phenotypes were derived among 20 189 total patients (16 552 unique patients) who met Sepsis-3 criteria within 6 hours of hospital presentation at 12 Pennsylvania hospitals (2010-2012) using consensus k means clustering applied to 29 variables. Reproducibility and correlation with biological parameters and clinical outcomes were assessed in a second database (2013-2014; n = 43 086 total patients and n = 31 160 unique patients), in a prospective cohort study of sepsis due to pneumonia (n = 583), and in 3 sepsis RCTs (n = 4737). EXPOSURES All clinical and laboratory variables in the electronic health record. MAIN OUTCOMES AND MEASURES Derived phenotype (α, β, γ, and δ) frequency, host-response biomarkers, 28-day and 365-day mortality, and RCT simulation outputs. RESULTS The derivation cohort included 20 189 patients with sepsis (mean age, 64 [SD, 17] years; 10 022 [50%] male; mean maximum 24-hour Sequential Organ Failure Assessment [SOFA] score, 3.9 [SD, 2.4]). The validation cohort included 43 086 patients (mean age, 67 [SD, 17] years; 21 993 [51%] male; mean maximum 24-hour SOFA score, 3.6 [SD, 2.0]). Of the 4 derived phenotypes, the α phenotype was the most common (n = 6625; 33%) and included patients with the lowest administration of a vasopressor; in the β phenotype (n = 5512; 27%), patients were older and had more chronic illness and renal dysfunction; in the γ phenotype (n = 5385; 27%), patients had more inflammation and pulmonary dysfunction; and in the δ phenotype (n = 2667; 13%), patients had more liver dysfunction and septic shock. Phenotype distributions were similar in the validation cohort. There were consistent differences in biomarker patterns by phenotype. In the derivation cohort, cumulative 28-day mortality was 287 deaths of 5691 unique patients (5%) for the α phenotype; 561 of 4420 (13%) for the β phenotype; 1031 of 4318 (24%) for the γ phenotype; and 897 of 2223 (40%) for the δ phenotype. Across all cohorts and trials, 28-day and 365-day mortality were highest among the δ phenotype vs the other 3 phenotypes (P < .001). In simulation models, the proportion of RCTs reporting benefit, harm, or no effect changed considerably (eg, varying the phenotype frequencies within an RCT of early goal-directed therapy changed the results from >33% chance of benefit to >60% chance of harm). CONCLUSIONS AND RELEVANCE In this retrospective analysis of data sets from patients with sepsis, 4 clinical phenotypes were identified that correlated with host-response patterns and clinical outcomes, and simulations suggested these phenotypes may help in understanding heterogeneity of treatment effects. Further research is needed to determine the utility of these phenotypes in clinical care and for informing trial design and interpretation.
Critical Care, Mar 19, 2013
![Research paper thumbnail of 13. Homeostasis cardiovascular y aproximación terapéutica al sistema cardiovascular, basada en la fisiología [Cardiovascular homeostasis and physiology-based therapeutic approach to the cardiovascular system]](https://attachments.academia-assets.com/113142427/thumbnails/1.jpg)
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Critical Care, 2008
Introduction In order to find out the frequency rates of domestic and wild animal bites as well a... more Introduction In order to find out the frequency rates of domestic and wild animal bites as well as the evaluation of the prevalence rates of rabies disease in the human population in the Province of Kerman, a retrospective study was designed to analyze statistically the collected recorded data related to this project. Methods This study was conducted within the framework of MPVM student research projects by means of collaboration between
Frontiers in Medicine, May 19, 2022
Introduction: Targeted therapies for sepsis have failed to show benefit due to high variability a... more Introduction: Targeted therapies for sepsis have failed to show benefit due to high variability among subjects. We sought to demonstrate different phenotypes of septic shock based solely on clinical features and show that these relate to outcome. Methods: A retrospective analysis was performed of a 1,023-subject cohort with early septic shock from the ProCESS trial. Twenty-three clinical variables at baseline were analyzed using hierarchical clustering, with consensus clustering used to identify and validate the ideal number of clusters in a derivation cohort of 642 subjects from 20 hospitals. Clusters were visualized using heatmaps over 0, 6, 24, and 72 h. Clinical outcomes were 14-day all-cause mortality and organ failure pattern. Cluster robustness was confirmed in a validation cohort of 381 subjects from 11 hospitals. Results: Five phenotypes were identified, each with unique organ failure patterns that persisted in time. By enrollment criteria, all patients had shock. The two high-risk phenotypes were characterized by distinct multi-organ failure patterns and cytokine signatures, with the highest mortality group characterized most notably by liver dysfunction and coagulopathy while the other group exhibited primarily respiratory failure, neurologic dysfunction, and renal dysfunction. The moderate risk phenotype was that of respiratory failure, while low-risk phenotypes did not have a high degree of additional organ failure. Conclusions: Sepsis phenotypes with distinct biochemical abnormalities may be identified by clinical characteristics alone and likely provide an opportunity for early clinical actionability and prognosis.
Nature Reviews Nephrology
Sepsis-associated acute kidney injury (SA-AKI) is common in critically ill patients and is strong... more Sepsis-associated acute kidney injury (SA-AKI) is common in critically ill patients and is strongly associated with adverse outcomes, including an increased risk of chronic kidney disease, cardiovascular events and death. The pathophysiology of SA-AKI remains elusive, although microcirculatory dysfunction, cellular metabolic reprogramming and dysregulated inflammatory responses have been implicated in preclinical studies. SA-AKI is best defined as the occurrence of AKI within 7 days of sepsis onset (diagnosed according to Kidney Disease Improving Global Outcome criteria and Sepsis 3 criteria, respectively). Improving outcomes in SA-AKI is challenging, as patients can present with either clinical or subclinical AKI. Early identification of patients at risk of AKI, or at risk of progressing to severe and/or persistent AKI, is crucial to the timely initiation of adequate supportive measures, including limiting further insults to the kidney. Accordingly, the discovery of biomarkers associated with AKI that can aid in early diagnosis is an area of intensive investigation. Additionally, high-quality evidence on best-practice care of patients with AKI, sepsis and SA-AKI has continued to accrue. Although specific therapeutic options are limited, several clinical trials have evaluated the use of care bundles and extracorporeal techniques as potential therapeutic approaches. Here we provide graded recommendations for managing SA-AKI and highlight priorities for future research.
Annals of Intensive Care, 2020
Background Weaning from mechanical ventilation (MV) is a cardiovascular stress test. Monitoring t... more Background Weaning from mechanical ventilation (MV) is a cardiovascular stress test. Monitoring the regional oxygenation status has shown promising results in predicting the tolerance to spontaneously breathe in the process of weaning from MV. Our aim was to determine whether changes in skeletal muscle oxygen saturation (StO2) measured by near-infrared spectroscopy (NIRS) on the thenar eminence during a vascular occlusion test (VOT) can be used to predict extubation failure from mechanical ventilation. Methods We prospectively studied 206 adult patients with acute respiratory failure receiving MV for at least 48 h from a 30-bed mixed ICU, who were deemed ready to wean by their physicians. Patients underwent a 30-min spontaneous breathing trial (SBT), and were extubated according to the local protocol. Continuous StO2 was measured non-invasively on the thenar eminence. A VOT was performed prior to and at 30 min of the SBT (SBT30). The rate of StO2 deoxygenation (DeO2), StO2 reoxygena...
IFAC-PapersOnLine, 2018
Renal function can become compromised in the event of shock, leading to acute kidney injury (AKI)... more Renal function can become compromised in the event of shock, leading to acute kidney injury (AKI). As a result, microcirculatory dysfunction and disruption of oxygen homeostastis is observed, which leads to a shift in mitochondrial bioenergetics. These events can be studied by assessing the functionality in healthy, normal states and diseased states. Characterization of the spatial heterogeneity of mitochondrial activity and capillary blood volume space in healthy renal cells was performed using intravital multi-photon microscopy. The developed metrics that were used for depiction and quantification of the physiologic normal state can be applied to a diseased state, allowing the extent of microcirculatory dysfunction to be observed and evaluated.
Kidney International, 2019
Sepsis-associated acute kidney injury (S-AKI) is a frequent complication of the critically ill pa... more Sepsis-associated acute kidney injury (S-AKI) is a frequent complication of the critically ill patient and is associated with unacceptable morbidity and mortality. Prevention of S-AKI is difficult because by the time patients seek medical attention, most have already developed acute kidney injury. Thus, early recognition is crucial to provide supportive treatment and limit further insults. Current diagnostic criteria for acute kidney injury has limited early detection; however, novel biomarkers of kidney stress and damage have been recently validated for risk prediction and early diagnosis of acute kidney injury in the setting of sepsis. Recent evidence shows that microvascular dysfunction, inflammation, and metabolic reprogramming are 3 fundamental mechanisms that may play a role in the development of S-AKI. However, more mechanistic studies are needed to better understand the convoluted pathophysiology of S-AKI and to translate these findings into potential treatment strategies and add to the promising pharmacologic approaches being developed and tested in clinical trials.
Critical Care Medicine, 2020
Introduction/Hypothesis: We have previously demonstrated that shedding of the glycocalyx increase... more Introduction/Hypothesis: We have previously demonstrated that shedding of the glycocalyx increases platelet adhesion in the renal peritubular capillaries resulting in acute kidney injury (AKI) regardless of the severity of the inflammatory response. We now hypothesized that blockade of Pselectin, a key endothelial adhesion molecule involved in leukocyte and platelet adhesion, would decrease platelet adhesion after glycocalyx shedding, resulting in improved microvascular and organ function. Methods: C57BL/6 (n=5-6/group) mice were assigned to control (vehicle or sham), hyaluronidase (Hyal: 140 IU IA q8h for 24 hours) as a model of sterile glycocalyx denudation, cecal ligation and puncture (CLP) as a model of sepsis. All groups received anti-P-selectin (P-sel) antibody (2mg/kg IA at 12 and 24hrs following initial injury). Outcomes were measured at 24hrs: Glycocalyx shedding and systemic inflammation were assessed using plasma syndecan-1 (SDC-1) (pg/ml) and IL-6 (pg/ml), respectively. Platelet adhesion in renal peritubular capillaries (# of platelets adhered longer than 10s per 100μm of capillary) was quantified using multiphoton intravital microscopy. Serum creatinine (sCr) (mg/dl) was used to evaluate renal injury. Results: Hyal and CLP resulted in increased SDC-1 levels (Cntl 421.1±87.04 vs Hyal 2134.2±530.4 p=0.02; Sham 535.7±146.1 vs CLP 4914±588.1; p<0.01), however, only CLP had an increase in IL-6 (Cntl 529.4±452.9 vs Hyal 353.8±89, p=0.43; Sham 508.7±258.7 vs CLP 7759±5528 p=0.03). Treatment with P-selectin following insult resulted in reduced platelet adhesion in the Hyal group and a trend in the CLP group (Hyal 2.47±2.12 vs Hyal+P-Sel 0.53±0.13 p=0.02; CLP 1.66±2.18 vs CLP+P-Sel 0.42±0.3 p=0.22) and decreased sCr levels in both groups (Hyal 1.48±0.82 vs Hyal+P-Sel 1.21±0.29 p=0.03; CLP 3.47±0.7 vs CLP+P-Sel 2.33±0.29 p=0.03). Conclusions: Glycocalyx shedding increases platelet adhesion, regardless of the severity of the systemic inflammatory response, resulting in microcirculatory dysfunction contributing to AKI. Blockade of P-selectin and platelets interaction results in decreased platelet adhesion and organ function improvement. These results suggest that platelet adhesion blockade constitutes a potential therapeutic target for microvascular dysfunction in sepsis induced AKI.
Circulation, Oct 28, 2008
Critical Care Medicine, Nov 9, 2020
Objective:To compare 5% albumin to 0.9% saline for large-volume resuscitation (LVR, > 60ml/Kg wit... more Objective:To compare 5% albumin to 0.9% saline for large-volume resuscitation (LVR, > 60ml/Kg within 24h), on mortality and development of acute kidney injury (AKI).Design:Retrospective cohort study.Setting:Patients admitted to intensive care units (ICUs) in 13 hospitals across Western Pennsylvania. We analyzed two independent cohorts, the High-Density Intensive Care (HiDenIC) databases: HiDenIC08 (July 2000 to October 2008, H08) and HiDenIC15 (October 2008 to December 2014, H15).Patients:Total of 18,629 critically ill patients requiring LVR.Interventions:5% albumin in addition to saline vs 0.9% saline.Measurements and Main Results:After excluding patients with AKI prior to LVR, 673/2,428 (27.7%) and 1,814/16,201 (11.2%) patients received 5% albumin in H08 and H15, respectively. Use of 5% albumin was associated with decreased 30-day mortality by multivariate regression in H08 (OR 0.65, 95% CI 0.49–0.85, p=0.002) and in H15 (0.52, 95% CI 0.44–0.62, p<0.0001), but was associated with increased AKI in H08 (OR 1.98, 95% CI 1.56–2.51, p<0.001) and in H15 (OR 1.75, 95% CI 1.58–1.95, p<0.001). However, 5% albumin was not associated with persistent AKI, and resulted in decreased MAKE at 30, 90 and 365 days. Propensity matched analysis confirmed similar associations with mortality and AKI.Conclusion:During LVR, 5% albumin was associated with reduced mortality and MAKE at 30, 90 and 365 days. However, a higher rate of AKI of any stage was observed that did not translate into persistent renal dysfunction.
Critical Care, Oct 18, 2017
All of medicine aspires to be precise, where a greater understanding of individual data will lead... more All of medicine aspires to be precise, where a greater understanding of individual data will lead to personalized treatment and improved outcomes. Prompted by specific examples in oncology, the field of critical care may be tempted to envision that complex, acute syndromes could bend to a similar reductionist philosophy-where single mutations could identify and target our critically ill patients for treatment. However, precision medicine faces many challenges in critical care. These include confusion about terminology, uncertainty about how to divide patients into discrete groups, the challenges of multi-morbidity, scale, and the need for timely interventions. This review addresses these challenges and provides a translational roadmap spanning preclinical work to identify putative treatment targets, novel designs for clinical trials, and the integration of the electronic health record to implement precision critical care for all.
Critical Care Medicine, Dec 16, 2021
Shock, Mar 1, 2016
Mitochondria are an essential part of the cellular infrastructure, being the primary site for hig... more Mitochondria are an essential part of the cellular infrastructure, being the primary site for high energy adenosine triphosphate (ATP) production through oxidative phosphorylation. Clearly, in severe systemic inflammatory states, like sepsis, cellular metabolism is usually altered and end organ dysfunction not only common but predictive of long term morbidity and mortality. Clearly, interest is mitochondrial function both as a target for intracellular injury and response to extrinsic stress have been a major focus of basic science and clinical research into the pathophysiology of acute illness. However, mitochondria have multiple metabolic and signaling functions that may be central in both the expression of sepsis and its ultimate outcome. In this review, the authors address five primary questions centered on the role of mitochondria in sepsis. This review should be used as both a summary source in placing mitochondrial physiology within the context of acute
JAMA, May 28, 2019
IMPORTANCE Sepsis is a heterogeneous syndrome. Identification of distinct clinical phenotypes may... more IMPORTANCE Sepsis is a heterogeneous syndrome. Identification of distinct clinical phenotypes may allow more precise therapy and improve care. OBJECTIVE To derive sepsis phenotypes from clinical data, determine their reproducibility and correlation with host-response biomarkers and clinical outcomes, and assess the potential causal relationship with results from randomized clinical trials (RCTs). DESIGN, SETTINGS, AND PARTICIPANTS Retrospective analysis of data sets using statistical, machine learning, and simulation tools. Phenotypes were derived among 20 189 total patients (16 552 unique patients) who met Sepsis-3 criteria within 6 hours of hospital presentation at 12 Pennsylvania hospitals (2010-2012) using consensus k means clustering applied to 29 variables. Reproducibility and correlation with biological parameters and clinical outcomes were assessed in a second database (2013-2014; n = 43 086 total patients and n = 31 160 unique patients), in a prospective cohort study of sepsis due to pneumonia (n = 583), and in 3 sepsis RCTs (n = 4737). EXPOSURES All clinical and laboratory variables in the electronic health record. MAIN OUTCOMES AND MEASURES Derived phenotype (α, β, γ, and δ) frequency, host-response biomarkers, 28-day and 365-day mortality, and RCT simulation outputs. RESULTS The derivation cohort included 20 189 patients with sepsis (mean age, 64 [SD, 17] years; 10 022 [50%] male; mean maximum 24-hour Sequential Organ Failure Assessment [SOFA] score, 3.9 [SD, 2.4]). The validation cohort included 43 086 patients (mean age, 67 [SD, 17] years; 21 993 [51%] male; mean maximum 24-hour SOFA score, 3.6 [SD, 2.0]). Of the 4 derived phenotypes, the α phenotype was the most common (n = 6625; 33%) and included patients with the lowest administration of a vasopressor; in the β phenotype (n = 5512; 27%), patients were older and had more chronic illness and renal dysfunction; in the γ phenotype (n = 5385; 27%), patients had more inflammation and pulmonary dysfunction; and in the δ phenotype (n = 2667; 13%), patients had more liver dysfunction and septic shock. Phenotype distributions were similar in the validation cohort. There were consistent differences in biomarker patterns by phenotype. In the derivation cohort, cumulative 28-day mortality was 287 deaths of 5691 unique patients (5%) for the α phenotype; 561 of 4420 (13%) for the β phenotype; 1031 of 4318 (24%) for the γ phenotype; and 897 of 2223 (40%) for the δ phenotype. Across all cohorts and trials, 28-day and 365-day mortality were highest among the δ phenotype vs the other 3 phenotypes (P < .001). In simulation models, the proportion of RCTs reporting benefit, harm, or no effect changed considerably (eg, varying the phenotype frequencies within an RCT of early goal-directed therapy changed the results from >33% chance of benefit to >60% chance of harm). CONCLUSIONS AND RELEVANCE In this retrospective analysis of data sets from patients with sepsis, 4 clinical phenotypes were identified that correlated with host-response patterns and clinical outcomes, and simulations suggested these phenotypes may help in understanding heterogeneity of treatment effects. Further research is needed to determine the utility of these phenotypes in clinical care and for informing trial design and interpretation.
Critical Care, Mar 19, 2013
Critical Care, 2008
Introduction In order to find out the frequency rates of domestic and wild animal bites as well a... more Introduction In order to find out the frequency rates of domestic and wild animal bites as well as the evaluation of the prevalence rates of rabies disease in the human population in the Province of Kerman, a retrospective study was designed to analyze statistically the collected recorded data related to this project. Methods This study was conducted within the framework of MPVM student research projects by means of collaboration between
Frontiers in Medicine, May 19, 2022
Introduction: Targeted therapies for sepsis have failed to show benefit due to high variability a... more Introduction: Targeted therapies for sepsis have failed to show benefit due to high variability among subjects. We sought to demonstrate different phenotypes of septic shock based solely on clinical features and show that these relate to outcome. Methods: A retrospective analysis was performed of a 1,023-subject cohort with early septic shock from the ProCESS trial. Twenty-three clinical variables at baseline were analyzed using hierarchical clustering, with consensus clustering used to identify and validate the ideal number of clusters in a derivation cohort of 642 subjects from 20 hospitals. Clusters were visualized using heatmaps over 0, 6, 24, and 72 h. Clinical outcomes were 14-day all-cause mortality and organ failure pattern. Cluster robustness was confirmed in a validation cohort of 381 subjects from 11 hospitals. Results: Five phenotypes were identified, each with unique organ failure patterns that persisted in time. By enrollment criteria, all patients had shock. The two high-risk phenotypes were characterized by distinct multi-organ failure patterns and cytokine signatures, with the highest mortality group characterized most notably by liver dysfunction and coagulopathy while the other group exhibited primarily respiratory failure, neurologic dysfunction, and renal dysfunction. The moderate risk phenotype was that of respiratory failure, while low-risk phenotypes did not have a high degree of additional organ failure. Conclusions: Sepsis phenotypes with distinct biochemical abnormalities may be identified by clinical characteristics alone and likely provide an opportunity for early clinical actionability and prognosis.
Nature Reviews Nephrology
Sepsis-associated acute kidney injury (SA-AKI) is common in critically ill patients and is strong... more Sepsis-associated acute kidney injury (SA-AKI) is common in critically ill patients and is strongly associated with adverse outcomes, including an increased risk of chronic kidney disease, cardiovascular events and death. The pathophysiology of SA-AKI remains elusive, although microcirculatory dysfunction, cellular metabolic reprogramming and dysregulated inflammatory responses have been implicated in preclinical studies. SA-AKI is best defined as the occurrence of AKI within 7 days of sepsis onset (diagnosed according to Kidney Disease Improving Global Outcome criteria and Sepsis 3 criteria, respectively). Improving outcomes in SA-AKI is challenging, as patients can present with either clinical or subclinical AKI. Early identification of patients at risk of AKI, or at risk of progressing to severe and/or persistent AKI, is crucial to the timely initiation of adequate supportive measures, including limiting further insults to the kidney. Accordingly, the discovery of biomarkers associated with AKI that can aid in early diagnosis is an area of intensive investigation. Additionally, high-quality evidence on best-practice care of patients with AKI, sepsis and SA-AKI has continued to accrue. Although specific therapeutic options are limited, several clinical trials have evaluated the use of care bundles and extracorporeal techniques as potential therapeutic approaches. Here we provide graded recommendations for managing SA-AKI and highlight priorities for future research.
Annals of Intensive Care, 2020
Background Weaning from mechanical ventilation (MV) is a cardiovascular stress test. Monitoring t... more Background Weaning from mechanical ventilation (MV) is a cardiovascular stress test. Monitoring the regional oxygenation status has shown promising results in predicting the tolerance to spontaneously breathe in the process of weaning from MV. Our aim was to determine whether changes in skeletal muscle oxygen saturation (StO2) measured by near-infrared spectroscopy (NIRS) on the thenar eminence during a vascular occlusion test (VOT) can be used to predict extubation failure from mechanical ventilation. Methods We prospectively studied 206 adult patients with acute respiratory failure receiving MV for at least 48 h from a 30-bed mixed ICU, who were deemed ready to wean by their physicians. Patients underwent a 30-min spontaneous breathing trial (SBT), and were extubated according to the local protocol. Continuous StO2 was measured non-invasively on the thenar eminence. A VOT was performed prior to and at 30 min of the SBT (SBT30). The rate of StO2 deoxygenation (DeO2), StO2 reoxygena...
IFAC-PapersOnLine, 2018
Renal function can become compromised in the event of shock, leading to acute kidney injury (AKI)... more Renal function can become compromised in the event of shock, leading to acute kidney injury (AKI). As a result, microcirculatory dysfunction and disruption of oxygen homeostastis is observed, which leads to a shift in mitochondrial bioenergetics. These events can be studied by assessing the functionality in healthy, normal states and diseased states. Characterization of the spatial heterogeneity of mitochondrial activity and capillary blood volume space in healthy renal cells was performed using intravital multi-photon microscopy. The developed metrics that were used for depiction and quantification of the physiologic normal state can be applied to a diseased state, allowing the extent of microcirculatory dysfunction to be observed and evaluated.
Kidney International, 2019
Sepsis-associated acute kidney injury (S-AKI) is a frequent complication of the critically ill pa... more Sepsis-associated acute kidney injury (S-AKI) is a frequent complication of the critically ill patient and is associated with unacceptable morbidity and mortality. Prevention of S-AKI is difficult because by the time patients seek medical attention, most have already developed acute kidney injury. Thus, early recognition is crucial to provide supportive treatment and limit further insults. Current diagnostic criteria for acute kidney injury has limited early detection; however, novel biomarkers of kidney stress and damage have been recently validated for risk prediction and early diagnosis of acute kidney injury in the setting of sepsis. Recent evidence shows that microvascular dysfunction, inflammation, and metabolic reprogramming are 3 fundamental mechanisms that may play a role in the development of S-AKI. However, more mechanistic studies are needed to better understand the convoluted pathophysiology of S-AKI and to translate these findings into potential treatment strategies and add to the promising pharmacologic approaches being developed and tested in clinical trials.