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Biomedical subjects

Lars H Lund

Publications and source records attributed to Lars H Lund.

10 recordsLinked to original sources
PubMed2026

Risk prediction in patients with heart failure with preserved ejection fraction: the LIFE-Preserved model.

BACKGROUND AND AIMS: Heart failure (HF) with preserved ejection fraction (HFpEF) constitutes a heterogeneous disease with varying prognosis. Given the rising incidence of HFpEF, accurate risk prediction for these patients is needed to identify high-risk individuals, who may benefit the most from preventive treatments. The LIFE-Preserved model was developed and validated for the prediction of individual short-term and lifetime risk for HF hospitalization or cardiovascular (CV) death in patients with HFpEF. METHODS: LIFE-Preserved was derived in 20 332 patients aged 40-90 years with a left ventricular ejection fraction ≥ 50% from the Swedish HF Registry. Cause- and sex-specific Cox models were derived to predict the risk of HF hospitalization or CV death using 14 routinely available predictors. Use of age as the timescale allowed for predictions beyond the maximum follow-up duration in the derivation data, adjusted for competing risks. External validation was performed in two trials (EMPEROR-Preserved and TOPCAT-Americas) and three registries (NHS England Secure Data Environment, Veterans Affairs, and HF-Particles). Model performance was assessed by discrimination and calibration. RESULTS: During a median follow-up of 1.8 years (interquartile range .6-4.2, maximum 19 years), 9341 first HF hospitalizations or CV deaths (46%) were observed in Swedish HF Registry. External validation included data from 28 062 patients with HFpEF [9930 (35%) first HF hospitalizations or CV deaths]. Pooled C-statistics were .714 (95% confidence interval .652-.775) in trials and .658 (95% confidence interval .599-.717 in registries, with adequate calibration in all external validation sources. Performance was similar in men and women. An interactive calculator of the LIFE-Preserved model has been made available here. CONCLUSIONS: The LIFE-Preserved model enables prediction of short-term and lifetime risk of HF hospitalization or CV death in patients with HFpEF. The model could serve as a tool to identify high-risk HFpEF patients, guiding clinical management and shared decision-making.

Humans↗
PubMed2005

Excessive weight gain in cardiac transplant recipients.

BACKGROUND: Substantial weight gain frequently occurs after cardiac transplant (CT) and increases the risk of secondary disease. It is unclear, however, if weight gain after CT is related to glucocorticoid immunosuppressive therapy. METHODS: A retrospective chart review was performed on the first 200 patients undergoing CT and the first 200 patients undergoing renal transplant (RT) at Columbia Presbyterian Medical Center, starting in January 2000. Patients who survived 1 year and had their weight recorded at transplant were included in the study. Rejection episodes and prednisone treatment was recorded for CT patients. Regression analysis was used to determine predictors of weight gain. RESULTS: A total of 158 CT patients and 128 RT patients were included in the data analysis. The weight of CT patients at time of transplant was (mean +/- SD) 76.3 +/- 14.6 kg and increased by 10.3 +/- 10.6 kg (p < 0.05) by 1-year post-transplant. Pre-transplant weight of the RT patients was 74.1 +/- 20.1 kg; by 1-year post-RT, weight increased by 3.5 +/- 8.6 kg (p < 0.05). The weight gain in CT patients was significantly greater than in the RT patients (p < 0.001). Post-transplant weight change in multiple regression models was related to age, gender (male) and transplant type (cardiac), but not to prednisone dose or pre-transplant weight. CONCLUSIONS: CT results in substantial post-surgical weight gain, which is greater than that observed for RT. Overweight and obesity development was not related to prednisone dose alone. This observation may have important clinical and research implications.

Adult↗
PubMed2005

Validation of peak exercise oxygen consumption and the Heart Failure Survival Score for serial risk stratification in advanced heart failure.

The Heart Failure Survival Score (HFSS) and peak exercise oxygen consumption (VO2) accurately assess mortality in ambulatory patients who have advanced heart failure and are referred for initial cardiac transplant evaluation. We investigated the prognostic value of the HFSS and peak VO2 when applied serially to these patients. This study included 227 adults (mean age +/- SD 52 +/- 10 years old) who presented for reevaluation >60 days after initial evaluation (352 +/- 238 days). The HFSS was determined from mean arterial blood pressure, heart rate, left ventricular ejection fraction, serum sodium, peak VO2, heart failure etiology, and width of QRS complex. Survival without reevaluation, United Network of Organ Sharing 1 transplant, or left ventricular assist device was determined by the Kaplan-Meier method with censoring at United Network of Organ Sharing 2 transplant. Survival differed by HFSS stratum (p <0.001) and by peak VO2 stratum (p <0.001). Patients whose HFSS or peak VO2 deteriorated from low risk to medium or high risk had lower survival rates than did patients whose values remained at low risk (p <0.01 and p <0.001, respectively). Patients who started at medium or high risk and improved to low risk tended to have higher survival rates than those who remained medium or high risk (p = 0.06 and p <0.16, respectively). Patients who improved to low risk had a 1-year survival rate of 72% for HFSS and peak VO2. However, patients who improved to low risk and were treated with beta blockers had a 1-year survival rate (89% for HFSS and 83% for peak VO2) comparable to that after transplant (84%). Peak VO2 and the HFSS can be successfully used for serial evaluation of mortality risk in ambulatory patients who have advanced heart failure.

Adult↗
PubMed2004

Primary murine cells as a model for HIV-1 infection.

Immortalized and transduced cell lines are traditionally used in model of the HIV-1 life cycle. Primary cells may better represent the tissue of origin and events in vivo. We utilized an HIV-1/murine leukemia A4070 pseudotype virus and human Cyclin T1 to replicate HIV-1 in primary murine cells, and demonstrate that primary murine cells support HIV-1 infection better than immortalized cells.

Animals↗
PubMed2004

Heart failure in women.

Women who experience heart failure (HF) exhibit distinct differences from men. Because women are a minority in major HF trials and because diagnostic criteria have been variable in epidemiologic surveys, many questions remain unanswered. This article describes differences in sex hormone effects and responses to injury, pressure overload, and aging, which may account for differences observed in epidemiology, risk factors and causes, mechanisms for disease development, response to treatment, and outcomes. Hypertension,diastolic dysfunction, diabetes, obesity, and inactivity are more important factors in women, whereas ischemic heart disease and systolic dysfunction are more important factors in men. Women appear to benefit less from established treatments but have better survival. Future studies directed exclusively at women may be warranted to confirm or establish benefits of existing and future treatments.

Adult↗
PubMed2003

Signal sequence deletion and fusion to tetanus toxoid epitope augment antitumor immune responses to a human carcinoembryonic antigen (CEA) plasmid DNA vaccine in a murine test system.

Carcinoembryonic antigen (CEA, CEACAM5) is expressed on several human carcinomas including colon cancer. CEA contains signal peptides that target the protein through the endoplasmic reticulum and to the cell membrane. We constructed a plasmid DNA vaccine encoding a truncated CEA (deltaCEA), devoid of its signal peptides, and demonstrated that it was retained inside the cell, while full-length CEA (wtCEA) was expressed on the membrane. We hypothesized that intracellular retention of deltaCEA would enhance MHC class I presentation of CEA peptides, thus favoring cellular immune responses. In addition, a promiscuous T-helper epitope (Q830-L844 of tetanus toxoid) was fused to the N-terminal of the truncated CEA gene (tetdeltaCEA). C57BL/6 mice immunized with DNA encoding wtCEA or tetdeltaCEA developed both humoral and cellular immune responses to CEA. SCID mice transplanted with spleen cells from tetdeltaCEA but not wtCEA-immunized C57BL/6 mice showed strong suppression of tumor growth after inoculation of human CEA-expressing colon carcinoma cells. Immune spleen cell populations depleted for either B, T or both B and T cells were active, indicating that effector cells might also reside in other populations. The present approach to manipulating antigen presentation may open new possibilities for immunotherapy against colon and other CEA-secreting carcinomas.

Animals↗
PubMed2003

A functional genetic approach suggests a novel interaction between the human immunodeficiency virus type 1 (HIV-1) Tat protein and HIV-1 TAR RNA in vivo.

Human immunodeficiency virus type 1 (HIV-1) Tat and human Cyclin T1 form a complex and together recognize the viral TAR RNA element with specificity. Using HIV-1/equine infectious anaemia virus TAR chimeras, we show that in addition to the well-characterized interaction with the bulge, Tat recognizes the distal stem and the loop of TAR. These data support previously proposed, but unproven, molecular models.

Animals↗
PubMed2002

A unique amino acid deletion in the chimpanzee Cyclin T1 does not affect Tat trans-activation of HIV.

We have cloned and sequenced the chimpanzee (Pan troglodytes) cyclin T1 cDNA and performed functional HIV-1 Tat trans-activation studies. A unique codon deletion leading to a deleted asparagine residue in the N-terminal region of the first cyclin domain was discovered. This mutation does not significantly change the trans-activation of HIV-1, suggesting that Tat-Cyclin T1 mediated transcription is not a major barrier to HIV replication in the chimpanzee.

Animals↗