An Inverse Marker of Morbidity and Mortality in Patients With Myocardial Infarction

[Posted 27/Oct/2023]

AUDIENCE: Internal Medicine, Cardiology

KEY FINDINGS: Patients with the highest LDL-C levels at MI had the lowest incidence of mortality and morbidity. This seems to reflect lower age at MI, less underlying morbidities, paired with the modifiability of LDL-C. However, supporting the causal association between LDL-C and ischemic heart disease, elevated LDL-C was simultaneously associated with an increased risk of nonfatal MI.

BACKGROUND: The incidence of atherosclerotic cardiovascular disease increases with levels of low-density lipoprotein cholesterol (LDL-C). Yet, a paradox may exist where lower LDL-C levels at myocardial infarction (MI) are associated with poorer prognoses. Aim of this study is to assess the association between LDL-C levels at MI with risk factor burden and cause-specific outcomes.

DETAILS: Statin-naive patients hospitalized for a first MI and registered in SWEDEHEART were included. Data were linked to Swedish registers. Primary outcomes were all-cause mortality and nonfatal MI. Associations between LDL-C and outcomes were assessed using adjusted proportional hazards models. Among 63,168 patients (median age, 66 years), the median LDL-C level was 3.0 mmol/L (interquartile range 2.4-3.6). Patient age and comorbidities increased as LDL-C decreased. During a median follow-up of 4.5 years, 10,236 patients died, and 4973 had nonfatal MI. Patients with the highest LDL-C had a lower risk of mortality (hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.71-0.80). The risk of hospitalization for pneumonia, hip fracture, chronic obstructive pulmonary disease, and new cancer diagnosis was lower with higher LDL-C (HR range, 0.40-0.81). Patients with the highest LDL-C had a greater risk of recurrent MI (HR 1.16; 95% CI 1.07-1.26).

Copyright © John Wiley & Sons, Inc. All rights reserved

Source: Schubert, J., Lindahl, B., Melhus, H., et al. (2023). Elevated Low-Density Lipoprotein Cholesterol: An Inverse Marker of Morbidity and Mortality in Patients With Myocardial Infarction. JIM. 2023; 294(5): 616-627. Published: November, 2023. DOI: 10.1111/joim.13656.

Definition of Syndrome-Specific Reference Ranges.

[Posted 13/Nov/2023]

AUDIENCE: Endocrinology, Pediatric, Family Medicine

KEY FINDINGS: By longitudinally assessing TFT in a wide pediatric DS population, we outlined the syndrome-specific reference nomograms for TSH, FT3, and FT4 and demonstrated a persistent upward shift of TSH compared to non-syndromic children.

BACKGROUND: The lack of syndrome-specific reference ranges for thyroid function tests (TFT) among pediatric patients with Down syndrome (DS) results in an overestimation of the occurrence of hypothyroidism in this population. Aim of this study is to (a) outline the age-dependent distribution of TFT among pediatric patients with DS; (b) describe the intraindividual variability of TFT over time; and (c) assess the role of elevated thyrotropin (TSH) in predicting the future onset of overt hypothyroidism.

DETAILS: In this retrospective, monocentric, observational analysis, authors included 548 patients with DS (0-18 years) longitudinally assessed between 1992 and 2022. Exclusion criteria were abnormal thyroid anatomy, treatments affecting TFT, and positive thyroid autoantibodies. Authors determined the age-dependent distribution of TSH, FT3, and FT4 and outlined the relative nomograms for children with DS. Compared with non-syndromic patients, median TSH levels were statistically greater at any age (P < .001). Median FT3 and FT4 levels were statistically lower than controls (P < .001) only in specific age classes (0-11 for FT3, 11-18 years for FT4). TSH levels showed a remarkable fluctuation over time, with a poor (23%-53%) agreement between the TSH centile classes at 2 sequential assessments. Finally, the 75th centile was the threshold above which TSH values predicted future evolution into overt hypothyroidism with the best statistical accuracy, with a satisfactory negative predictive value (0.91), but poor positive predictive value (0.15).

Copyright © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved.

Source: Cattoni, A., Molinari, S., Capitoli, G., et al. (2023). Thyroid Function Tests in Children and Adolescents With Trisomy 21: Definition of Syndrome-Specific Reference Ranges. JCEM. 2023; 108(11): 2779-2788. Published: November, 2023. DOI: 10.1210/clinem/dgad333.

Analysis of the Radiotherapy Strategies of the CWS-96 and CWS-2002P Studies and SoTiSaR Registry.

[Posted 6/Nov/2023]

AUDIENCE: Oncology, Pediatric

KEY FINDINGS: RT can be omitted in patients with IRS I eRMS. RT improves LCS and EFS in IRS II and III. RT improves OS in patients with HN-PM, with proton RT comparable with photon RT. Doses of 32 Gy (HART) or 36 and 41.4 Gy (CFRT) had comparable efficacy in patients with favorable risk profiles and 44.8 Gy (HART) or 50.4 and 55.8 Gy (CFRT) in the unfavorable groups.

BACKGROUND: Objective of this study is to analyze and compare the indications, doses, and application methods of radiotherapy (RT) and their influence on prognosis of patients with localized rhabdomyosarcoma (RMS). Radiotherapy (RT) is one of the local control modalities in patients with rhabdomyosarcoma (RMS) but is associated with severe acute and late toxicities. Authors have analyzed and compared the indications, doses, and application methods of RT and their influence on prognosis for patients with localized RMS.

DETAILS: One thousand four hundred seventy patients with localized RMS 21 years and younger entered on CWS-96, CWS-2002P, and SoTiSaR were eligible for the analysis. The median follow-up was 6.5 years (IQR, 3.3-9.5). The 5-year event-free survival (EFS) and local control survival (LCS) for 910 (62%) irradiated versus nonirradiated patients were 71% versus 69% and 78% versus 73% (P = .03), respectively. Ninety-five percent of patients in IRS I (90% embryonal RMS [eRMS]) were nonirradiated (EFS, 87%). Irradiated patients with IRS II had improved LCS (91% v 80%; P = .01) and EFS (not significant). In IRS III, EFS and LCS were significantly better for RT patients: 71% versus 56% (P = 3.1e-06) and 76% versus 61% (P = 4.1e-07). Patients with tumors in the head and neck region (orbita, parameningeal, and nonparameningeal) and in other sites had significantly better EFS and LCS and in parameningeal also overall survival (OS). The efficacy of low RT doses of 32 Gy (hyperfractionated, accelerated RT [HART]) and 36 and 41.4 Gy (conventional fractionated RT [CFRT]) in the favorable groups and higher doses of 44.8 Gy (HART) and 50.4 and 55.4 Gy (CFRT) in the unfavorable groups was comparable. Proton RT was used predominantly in head/neck-parameningeal (HN-PM) tumors, with similar EFS and LCS to photon RT.

Copyright © American Society of Clinical Oncology. All rights reserved.

Source: Koscielniak, E., Timmermann, B., Munter, M., et al. (2023). Which Patients With Rhabdomyosarcoma Need Radiotherapy? Analysis of the Radiotherapy Strategies of the CWS-96 and CWS-2002P Studies and SoTiSaR Registry. J Clinical Oncology. 2023; 41(31): 4916-4926.Published: November 1, 2023. DOI: 10.1200/JCO.22.02673.

[Posted 23/Oct/2023]

AUDIENCE: Nursing

KEY FINDINGS: Prompt pharmacologic intervention for pain, as well as further coaching and education about pain management should be emphasized for nurses caring for living kidney donors. Further study of how donor’s motivation might mediate their pain experience is needed.

BACKGROUND: This study employed a qualitative descriptive approach to examine living kidney donor’s experience of postoperative pain. Thirteen living kidney donors aged 46.5 (±14.4) years participated in this study.

DETAILS: Semi-structured interviews were conducted and transcribed. Transcripts were inductively coded and reviewed for trends, patterns, and insights into donor’s experience of postoperative pain. Donors experienced postoperative pain from a variety of sources that hindered recovery and created anxiety and fear in some. Donors managed pain with opioid and non-opioid medications, social support, and ambulation. Donor’s past experiences with and expectations about pain, relationships with intended recipients, social support, as well as motivations for and meaning of donation informed their experience of postoperative pain.

Copyright © SAGE Publications. All rights reserved.

Source: Dreesmann, N. J., Jung, W., Shebaili, M., et al. (2023). Kidney Donor Perspectives on Acute Postoperative Pain Management. Clinical Nursing Research. 2023; 32(8): 1124-1133. Published: November, 2023. DOI: 10.1177/105477382311561.

[Posted 31/Oct/2023]

AUDIENCE: Hematology, Family Medicine

KEY FINDINGS: Myeloablative fractionated busulfan regimen results in low nonrelapse mortality without a higher relapse rate. This regimen is a viable myeloablative alternative for patients who receive a reduced intensity regimen because of age or comorbidity.

BACKGROUND: Traditional conditioning regimens for patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) provide suboptimal outcomes, especially for older patients and those with comorbidities. We hypothesized that a fractionated myeloablative busulfan dose delivered over an extended period would reduce nonrelapse mortality (NRM) while retaining antileukemic effects.

DETAILS: Authors performed a phase 2 trial for adults with hematological malignancies receiving matched related or unrelated allo-HCT. Participants received busulfan 80 mg/m² as outpatients on days -20 and -13 before transplant. Fludarabine 40 mg/m² was administered on days -6 to -3, followed by busulfan dosed to achieve a target area under the curve of 20,000 mol/min for the whole course. The primary end point was day-100 NRM. Seventy-eight patients were included, with a median age of 61 years (range, 39-70 years), who received transplantation for acute leukemia (24%), myelodysplastic syndrome (27%), or myeloproliferative disease/chronic myeloid leukemia (44%). HCT-specific comorbidity index (HCT-CI) was >=3 in 34 (44%). With a median follow-up of 36.4 months (range, 2.9-51.5), the 100-day, 1-year, and 3-year NRM rates were 3.8%, 8%, and 9.3%, respectively, without a significant difference in age or HCT-CI score. The 1-year and 3-year relapse incidence was 10% and 18%, respectively. The 3-year overall survival was 80%, without a significant difference in age or HCT-CI score and was similar for patients aged >60 years and those aged <60 years as well as for those with HCT-CI >=3 and HCT-CI <3. Overall, a myeloablative fractionated busulfan regimen has low NRM without an increase in relapse rate, resulting in promising survival, even in older patients or in patients with comorbidities.

Copyright © The American Society of Hematology. All rights reserved.

Source: Popat, U. R., Pasvolsky, O., Nassett, R. Jr., et al. (2023). Myeloablative Fractionated Busulfan For Allogeneic Stem Cell Transplant In Older Patients Or Patients With Comorbidities. Blood Adv.. 2023; 7(20): 6196-6205. Published: October, 2023. DOI: 10.1182/bloodadvances.2023010850.

[Posted 26/Oct/2023]

AUDIENCE: Pediatric, Neurology, Family Medicine

KEY FINDINGS: During TH, cerebral glucose concentration is partly dependent on blood glucose concentration. Further studies to understand brain glucose use and optimal glucose concentrations during hypothermic neuroprotection are needed.

BACKGROUND: Objective of this study is to determine cerebral glucose concentration and its relationship with glucose infusion rate (GIR) and blood glucose concentration in neonatal encephalopathy during therapeutic hypothermia (TH).

DETAILS: This was an observational study in which cerebral glucose during TH was quantified by magnetic resonance (MR) spectroscopy and compared with mean blood glucose at the time of scan. Clinical data (gestational age, birth weight, GIR, sedative use) that could affect glucose use were collected. The severity and pattern of brain injury on MR imaging were scored by a neuroradiologist. Student t test, Pearson correlation, repeated measures ANOVA, and multiple regression analysis were performed. Three-hundred-sixty blood glucose values and 402 MR spectra from 54 infants (30 female infants; mean gestational age 38.6 ± 1.9 weeks) were analyzed. In total, 41 infants had normal-mild and 13 had moderate-severe injury. Median GIR and blood glucose during TH were 6.0 mg/kg/min (IQR 5-7) and 90 mg/dL (IQR 80-102), respectively. GIR did not correlate with blood or cerebral glucose. Cerebral glucose was significantly greater during than after TH (65.9 ± 22.9 vs 60.0 ± 25.2 mg/dL, P < .01), and there was a significant correlation between blood glucose and cerebral glucose during TH (basal ganglia: r = 0.42, thalamus: r = 0.42, cortical gray matter: r = 0.39, white matter: r = 0.39, all P < .01). There was no significant difference in cerebral glucose concentration in relation to injury severity or pattern.

Copyright © Elsevier Inc. All rights reserved.

Source: Tetarbe, M., Wisnowski, J. L., Geyer, E., et al. (2023). Cerebral Glucose Concentration in Neonatal Hypoxic-Ischemic Encephalopathy during Therapeutic Hypothermia. J Pediatr.. Published: October, 2023. DOI: 10.1016/j.jpeds.2023.113560.