Gundars Katlaps - Academia.edu (original) (raw)

Papers by Gundars Katlaps

BackgroundMast-Cell Expressed Membrane Protein-1 (MCEMP1) is higher in Idiopathic Pulmonary Fibro... more BackgroundMast-Cell Expressed Membrane Protein-1 (MCEMP1) is higher in Idiopathic Pulmonary Fibrosis (IPF) patients with increased risk of death and poor outcomes. Here we seek to establish the mechanistic role of MCEMP1 in pulmonary fibrosis.MethodsMCEMP1 expression was analyzed by single-cell RNA sequencing, immunofluorescence in Peripheral Blood Mononuclear Cells (PBMC) as well as in lung tissues from IPF patients and controls. Chromatin Immunoprecipitation (ChiP) and Proximity Ligation Assay (PLA) were used to study the transcriptional regulation ofMCEMP1. Transient RNA interference and lentivirus transduction were used to knockdown and knock-in MCEMP1 in THP-1 cells to study chemotaxis, adhesion, and migration. Bulk RNA sequencing was used to identify the mechanisms by which MCEMP1 participates in monocyte function. Active RHO pull-down assay was used to validate bulk RNA sequencing results.ResultsWe identified increased MCEMP1 expression in classical monocytes and alveolar mac...

PubMed, Jun 1, 2017

This study found significant improvements in heart transplant outcomes and survival in patients w... more This study found significant improvements in heart transplant outcomes and survival in patients with hepatitis C virus.

Journal of Heart and Lung Transplantation, Apr 1, 2014

Journal of Heart and Lung Transplantation, Apr 1, 2013

The Journal of Heart and Lung Transplantation, 2012

two-year survival post LVAD implantation did not differ between the pacing groups, censored or un... more two-year survival post LVAD implantation did not differ between the pacing groups, censored or uncensored for cardiac transplantation. Conclusions: Although this study is non-randomized and observational, there is no evidence that a substantial physiological or survival advantage exists for CRT after LVAD placement. These findings have important implications for choice and appropriateness of pacing therapy following LVAD implantation.

The Journal of Heart and Lung Transplantation, 2012

Purpose: The total artificial heart (TAH) orthotopically replaces the cardiac ventricles, interru... more Purpose: The total artificial heart (TAH) orthotopically replaces the cardiac ventricles, interrupting neural and hormonal signaling pathways dependent upon the myocardium. We hypothesized that repletion of BNP after ventriculectomy would improve renal function and increase urine output.

Journal of Heart and Lung Transplantation, Apr 1, 2017

The median distance for local donors was 86.13 miles vs 744.13 miles for expanded DSA. Ischemic t... more The median distance for local donors was 86.13 miles vs 744.13 miles for expanded DSA. Ischemic times were significantly longer for the group over 500 miles. There was no difference in actuarial recipient survival between the two groups over a 5-year follow-up (Figure 1). Blood type O donors were used more often locally (p= 0.004). The median age of donors < 500 miles was 29 years (y); 30 y > 500 miles. There was no difference in donor age (p< 0.0001). Median local donor Body Mass Index (BMI) was nearly identical 26.6 vs 25.8 for expanded DSA (p= 0.0027). Mean waiting time for Status 1A was 25 days (d) for recipients who received local donors vs 13d for expanded DSA donor recipients (p= 0.0037). The majority of donors in both groups were Caucasian (64.36%). More female donors were used in the expanded DSA (28.16% vs 41.23%; p= 0.0037). More female recipients received more female donors in the expanded DSA (24.89% vs 35.71%; p= 0.0029). There was no difference in recipients treated for rejection in the first year (19.48% vs 22.87%; p= 0.0004). Conclusion: 5 year survival using donors from less than or greater than 500 miles DSA was identical. Using donors from > 500 miles shortened the waiting time for status I A recipients by 12 days and increased the use of female donors and recipients.

Journal of Heart and Lung Transplantation, Apr 1, 2017

Purpose: There exists significant variability in donor heart offer and acceptance patterns across... more Purpose: There exists significant variability in donor heart offer and acceptance patterns across the United States, despite a severe donor organ shortage. We characterized current practices by analyzing the UNOS heart transplant registry from 2007-15, using Potential Transplant Recipient (PTR) data with OPO and transplant center identifiers, to examine donor heart offers, including the OPO that offered the organ, the centers to which the heart was offered, and the sequence number at which the organ was accepted. Methods: If a donor heart was never accepted for transplantation or if the heart was refused for a reason unrelated to the donor, we treated the organ sequence number as right censored. We modeled the number of times a heart was offered before it was finally accepted, accounting for censoring, with a hypergeometric distribution using the hurdle() function in R and assessed significance at the 0.05 level. Using the same framework, we investigated how transplant center volume was associated with the number of offers prior to acceptance. Results: We studied 21,179 heart offers from donors 18 years or older. Of these, 99% were accepted for transplant with the majority (67%) accepted by the 5th offer (median= 3, IQR 1-8). The predominant reasons for heart decline were donor age, hypertension, prolonged hypotension, high vasopressor dose, cardiac arrest, infection, diabetes, and other medical history. Multiracial and Black ethnicity were associated with higher numbers of offers prior to acceptance. Of the 145 transplant centers, 56% were classified as very low volume (< 12 transplants/year), 26% low (13-21/yr), 9% medium (22-33/yr), and 9% high volume (≥ 34/yr). High volume centers had a greater number of offers prior to acceptance (median 4, IQR 2-16), compared to very-low and low volume centers (median 2, IQR 1-6). Most donors (16%) came from UNOS Region 5 and the fewest donors (4% and 3%) came from Regions 1 and 6. Regions 1, 2, 7, 9, 10, 11 had a higher number of offers prior to acceptance, while Regions 3, 5, 6, and 8 had fewer offers prior to acceptance. Conclusion: We identified donor predictors of heart non-acceptance for transplant, and found significant variation among transplant centers and UNOS regions in donor heart acceptance. Higher volume centers accepted hearts with higher sequence number, suggesting a greater willingness to use higher risk donor hearts.

C32. INTERROGATION OF GENETIC VARIATION, GENE EXPRESSION, AND OTHER BIOLOGICAL LAYERS WITH OMICS TECHNIQUES TO UNDERSTAND RESPIRATORY TRAITS

Arteriosclerosis, Thrombosis, and Vascular Biology, 2013

Objectives Advances in cardiac surgery have significantly improved the outcomes for patients with... more Objectives Advances in cardiac surgery have significantly improved the outcomes for patients with myocardial ischemia. However, ischemia/ reperfusion injury represents a mechanism that continues to limit the effectiveness of coronary bypass graft surgery (CABG). Phosphodiesterase 5 inhibitors have been shown to exhibit powerful cardioprotective effects in animal models of ischemia-reperfusion injury. We evaluated the safety of vardenafil in patients undergoing cardiac surgery. Methods 10 male patients undergoing CABG with or without valve surgery were enrolled in the study. Subjects were given a onetime dose of 10 mg oral vardenafil on the morning of surgery. They were monitored for adverse events and left ventricular ejection fraction changes; pertinent clinical parameters were also recorded. Their postoperative parameters and outcomes were also compared with 47 patients who underwent CABG in the same period of time (control group). Results The study drug was tolerated well. There ...

Federal practitioner : for the health care professionals of the VA, DoD, and PHS, 2017

This study found significant improvements in heart transplant outcomes and survival in patients w... more This study found significant improvements in heart transplant outcomes and survival in patients with hepatitis C virus.

The Journal of Heart and Lung Transplantation, 2016

An important factor in patient selection for both LVAD support and HTx is patient's body mass ind... more An important factor in patient selection for both LVAD support and HTx is patient's body mass index (BMI). The 2013 International Society for Heart and Lung Transplantation (ISHLT) guidelines for mechanical circulatory support (MCS) state that "surgical risk and attendant comorbidities must be carefully considered prior to MCS in the morbidly obese patient (BMI ≥ 35) [5]".

The Journal of Heart and Lung Transplantation, 2014

The Annals of Thoracic Surgery

General Thoracic and Cardiovascular Surgery

Journal of cardiac failure, Jan 27, 2016

Insufficient data delineate outcomes for Interagency Registry for Mechanically Assisted Circulato... more Insufficient data delineate outcomes for Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 patients with the total artificial heart (TAH). We studied sixty-six consecutive patients implanted with the TAH at our institution from 2006-2012, and compared outcome by INTERMACS profile. INTERMACS profiles were adjudicated retrospectively by a reviewer blinded to clinical outcomes. Survival after TAH implantation at 6 and 12 months was 76% and 71%, respectively. INTERMACS profile 1 patients had decreased 6-month survival on the device compared to those in profiles 2-4 (74% vs 95%, log rank: p=0.015). For the 50 patients surviving to heart transplantation, the 1-year post-transplant survival was 82%. There was no difference in 1-year survival when comparing patients in the INTERMACS 1 profile to less severe profiles (79% vs. 84%; log rank test p=0.7; HR[CI]: 1.3 [0.3,4.8]). Patients implanted with the TAH as INTERMACS profile 1 had reduced survival to ...

Current Heart Failure Reports, 2011

BackgroundMast-Cell Expressed Membrane Protein-1 (MCEMP1) is higher in Idiopathic Pulmonary Fibro... more BackgroundMast-Cell Expressed Membrane Protein-1 (MCEMP1) is higher in Idiopathic Pulmonary Fibrosis (IPF) patients with increased risk of death and poor outcomes. Here we seek to establish the mechanistic role of MCEMP1 in pulmonary fibrosis.MethodsMCEMP1 expression was analyzed by single-cell RNA sequencing, immunofluorescence in Peripheral Blood Mononuclear Cells (PBMC) as well as in lung tissues from IPF patients and controls. Chromatin Immunoprecipitation (ChiP) and Proximity Ligation Assay (PLA) were used to study the transcriptional regulation ofMCEMP1. Transient RNA interference and lentivirus transduction were used to knockdown and knock-in MCEMP1 in THP-1 cells to study chemotaxis, adhesion, and migration. Bulk RNA sequencing was used to identify the mechanisms by which MCEMP1 participates in monocyte function. Active RHO pull-down assay was used to validate bulk RNA sequencing results.ResultsWe identified increased MCEMP1 expression in classical monocytes and alveolar mac...

PubMed, Jun 1, 2017

This study found significant improvements in heart transplant outcomes and survival in patients w... more This study found significant improvements in heart transplant outcomes and survival in patients with hepatitis C virus.

Journal of Heart and Lung Transplantation, Apr 1, 2014

Journal of Heart and Lung Transplantation, Apr 1, 2013

The Journal of Heart and Lung Transplantation, 2012

two-year survival post LVAD implantation did not differ between the pacing groups, censored or un... more two-year survival post LVAD implantation did not differ between the pacing groups, censored or uncensored for cardiac transplantation. Conclusions: Although this study is non-randomized and observational, there is no evidence that a substantial physiological or survival advantage exists for CRT after LVAD placement. These findings have important implications for choice and appropriateness of pacing therapy following LVAD implantation.

The Journal of Heart and Lung Transplantation, 2012

Purpose: The total artificial heart (TAH) orthotopically replaces the cardiac ventricles, interru... more Purpose: The total artificial heart (TAH) orthotopically replaces the cardiac ventricles, interrupting neural and hormonal signaling pathways dependent upon the myocardium. We hypothesized that repletion of BNP after ventriculectomy would improve renal function and increase urine output.

Journal of Heart and Lung Transplantation, Apr 1, 2017

The median distance for local donors was 86.13 miles vs 744.13 miles for expanded DSA. Ischemic t... more The median distance for local donors was 86.13 miles vs 744.13 miles for expanded DSA. Ischemic times were significantly longer for the group over 500 miles. There was no difference in actuarial recipient survival between the two groups over a 5-year follow-up (Figure 1). Blood type O donors were used more often locally (p= 0.004). The median age of donors < 500 miles was 29 years (y); 30 y > 500 miles. There was no difference in donor age (p< 0.0001). Median local donor Body Mass Index (BMI) was nearly identical 26.6 vs 25.8 for expanded DSA (p= 0.0027). Mean waiting time for Status 1A was 25 days (d) for recipients who received local donors vs 13d for expanded DSA donor recipients (p= 0.0037). The majority of donors in both groups were Caucasian (64.36%). More female donors were used in the expanded DSA (28.16% vs 41.23%; p= 0.0037). More female recipients received more female donors in the expanded DSA (24.89% vs 35.71%; p= 0.0029). There was no difference in recipients treated for rejection in the first year (19.48% vs 22.87%; p= 0.0004). Conclusion: 5 year survival using donors from less than or greater than 500 miles DSA was identical. Using donors from > 500 miles shortened the waiting time for status I A recipients by 12 days and increased the use of female donors and recipients.

Journal of Heart and Lung Transplantation, Apr 1, 2017

Purpose: There exists significant variability in donor heart offer and acceptance patterns across... more Purpose: There exists significant variability in donor heart offer and acceptance patterns across the United States, despite a severe donor organ shortage. We characterized current practices by analyzing the UNOS heart transplant registry from 2007-15, using Potential Transplant Recipient (PTR) data with OPO and transplant center identifiers, to examine donor heart offers, including the OPO that offered the organ, the centers to which the heart was offered, and the sequence number at which the organ was accepted. Methods: If a donor heart was never accepted for transplantation or if the heart was refused for a reason unrelated to the donor, we treated the organ sequence number as right censored. We modeled the number of times a heart was offered before it was finally accepted, accounting for censoring, with a hypergeometric distribution using the hurdle() function in R and assessed significance at the 0.05 level. Using the same framework, we investigated how transplant center volume was associated with the number of offers prior to acceptance. Results: We studied 21,179 heart offers from donors 18 years or older. Of these, 99% were accepted for transplant with the majority (67%) accepted by the 5th offer (median= 3, IQR 1-8). The predominant reasons for heart decline were donor age, hypertension, prolonged hypotension, high vasopressor dose, cardiac arrest, infection, diabetes, and other medical history. Multiracial and Black ethnicity were associated with higher numbers of offers prior to acceptance. Of the 145 transplant centers, 56% were classified as very low volume (< 12 transplants/year), 26% low (13-21/yr), 9% medium (22-33/yr), and 9% high volume (≥ 34/yr). High volume centers had a greater number of offers prior to acceptance (median 4, IQR 2-16), compared to very-low and low volume centers (median 2, IQR 1-6). Most donors (16%) came from UNOS Region 5 and the fewest donors (4% and 3%) came from Regions 1 and 6. Regions 1, 2, 7, 9, 10, 11 had a higher number of offers prior to acceptance, while Regions 3, 5, 6, and 8 had fewer offers prior to acceptance. Conclusion: We identified donor predictors of heart non-acceptance for transplant, and found significant variation among transplant centers and UNOS regions in donor heart acceptance. Higher volume centers accepted hearts with higher sequence number, suggesting a greater willingness to use higher risk donor hearts.

C32. INTERROGATION OF GENETIC VARIATION, GENE EXPRESSION, AND OTHER BIOLOGICAL LAYERS WITH OMICS TECHNIQUES TO UNDERSTAND RESPIRATORY TRAITS

Arteriosclerosis, Thrombosis, and Vascular Biology, 2013

Objectives Advances in cardiac surgery have significantly improved the outcomes for patients with... more Objectives Advances in cardiac surgery have significantly improved the outcomes for patients with myocardial ischemia. However, ischemia/ reperfusion injury represents a mechanism that continues to limit the effectiveness of coronary bypass graft surgery (CABG). Phosphodiesterase 5 inhibitors have been shown to exhibit powerful cardioprotective effects in animal models of ischemia-reperfusion injury. We evaluated the safety of vardenafil in patients undergoing cardiac surgery. Methods 10 male patients undergoing CABG with or without valve surgery were enrolled in the study. Subjects were given a onetime dose of 10 mg oral vardenafil on the morning of surgery. They were monitored for adverse events and left ventricular ejection fraction changes; pertinent clinical parameters were also recorded. Their postoperative parameters and outcomes were also compared with 47 patients who underwent CABG in the same period of time (control group). Results The study drug was tolerated well. There ...

Federal practitioner : for the health care professionals of the VA, DoD, and PHS, 2017

This study found significant improvements in heart transplant outcomes and survival in patients w... more This study found significant improvements in heart transplant outcomes and survival in patients with hepatitis C virus.

The Journal of Heart and Lung Transplantation, 2016

An important factor in patient selection for both LVAD support and HTx is patient's body mass ind... more An important factor in patient selection for both LVAD support and HTx is patient's body mass index (BMI). The 2013 International Society for Heart and Lung Transplantation (ISHLT) guidelines for mechanical circulatory support (MCS) state that "surgical risk and attendant comorbidities must be carefully considered prior to MCS in the morbidly obese patient (BMI ≥ 35) [5]".

The Journal of Heart and Lung Transplantation, 2014

The Annals of Thoracic Surgery

General Thoracic and Cardiovascular Surgery

Journal of cardiac failure, Jan 27, 2016

Insufficient data delineate outcomes for Interagency Registry for Mechanically Assisted Circulato... more Insufficient data delineate outcomes for Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 patients with the total artificial heart (TAH). We studied sixty-six consecutive patients implanted with the TAH at our institution from 2006-2012, and compared outcome by INTERMACS profile. INTERMACS profiles were adjudicated retrospectively by a reviewer blinded to clinical outcomes. Survival after TAH implantation at 6 and 12 months was 76% and 71%, respectively. INTERMACS profile 1 patients had decreased 6-month survival on the device compared to those in profiles 2-4 (74% vs 95%, log rank: p=0.015). For the 50 patients surviving to heart transplantation, the 1-year post-transplant survival was 82%. There was no difference in 1-year survival when comparing patients in the INTERMACS 1 profile to less severe profiles (79% vs. 84%; log rank test p=0.7; HR[CI]: 1.3 [0.3,4.8]). Patients implanted with the TAH as INTERMACS profile 1 had reduced survival to ...

Current Heart Failure Reports, 2011