A Propensity-Matched Cohort Study of Intravenous Iron versus Red Cell Transfusions for Preoperative Iron-Deficiency Anemia.

BACKGROUND: While preoperative anemia is associated with adverse perioperative outcomes, the benefits of treatment with iron replacement versus red blood cell (RBC) transfusion remain uncertain. We used a national database to establish trends in preoperative iron-deficiency anemia (IDA) treatment and to test the hypothesis that treatment with preoperative iron may be superior to RBC transfusion. METHODS: This study is a propensity-matched retrospective cohort analysis from 2003 to 2023 using TriNetX Research Network, which included surgical patients diagnosed with IDA within 3 months preoperatively. After matching for surgery type and comorbidities, we compared a cohort of patients with preoperative IDA who were treated with preoperative intravenous (IV) iron but not RBCs (n = 77,179), with a cohort receiving preoperative RBCs but not IV iron (n = 77,179). Propensity-score matching was performed for age, ethnicity, race, sex, overweight and obesity, type 2 diabetes, hyperlipidemia, essential hypertension, heart failure, chronic ischemic heart disease, neoplasms, hypothyroidism, chronic kidney disease, nicotine dependence, surgery type, and lab values from the day of surgery including ferritin, transferrin, and hemoglobin split into low (<7 g/dL), medium (7-<12 g/dL), and high (≥12 g/dL) to account for anemia severity. The primary outcome was 30-day postoperative mortality with the secondary outcomes being 30-day morbidity, postoperative hemoglobin level, and 30-day postoperative RBC transfusion. RESULTS: Compared with RBC transfusion, preoperative IV iron was associated with lower risk of postoperative mortality (n = 2550/77,179 [3.3%] vs n = 4042/77,179 [5.2%]; relative risk [RR], 0.63, 95% confidence interval [CI], 0.60-0.66), and a lower risk of postoperative composite morbidity (n = 14,174/77,179 [18.4%] vs n = 18,632/77,179 [24.1%]; RR, 0.76, 95% CI, 0.75-0.78) (both P = .001 after Bonferroni adjustment). Compared with RBC transfusion, IV iron was also associated with a higher hemoglobin in the 30-day postoperative period (10.1 ± 1.8 g/dL vs 9.4 ± 1.7 g/dL, P = .001 after Bonferroni adjustment) and a reduced incidence of postoperative RBC transfusion (n = 3773/77,179 [4.9%] vs n = 12,629/77,179 [16.4%]; RR, 0.30, 95% CI, 0.29-0.31). CONCLUSIONS: In a risk-adjusted analysis, preoperative IDA treatment with IV iron compared to RBC transfusion was associated with a reduction in 30-day postoperative mortality and morbidity, a higher 30-day postoperative hemoglobin level, and reduced postoperative RBC transfusion. This evidence represents a promising opportunity to improve patient outcomes and reduce blood transfusions and their associated risk and costs.

DNA mismatch and damage patterns revealed by single-molecule sequencing.

Mutations accumulate in the genome of every cell of the body throughout life, causing cancer and other diseases1,2. Most mutations begin as nucleotide mismatches or damage in one of the two strands of the DNA before becoming double-strand mutations if unrepaired or misrepaired3,4. However, current DNA-sequencing technologies cannot accurately resolve these initial single-strand events. Here we develop a single-molecule, long-read sequencing method (Hairpin Duplex Enhanced Fidelity sequencing (HiDEF-seq)) that achieves single-molecule fidelity for base substitutions when present in either one or both DNA strands. HiDEF-seq also detects cytosine deamination-a common type of DNA damage-with single-molecule fidelity. We profiled 134 samples from diverse tissues, including from individuals with cancer predisposition syndromes, and derive from them single-strand mismatch and damage signatures. We find correspondences between these single-strand signatures and known double-strand mutational signatures, which resolves the identity of the initiating lesions. Tumours deficient in both mismatch repair and replicative polymerase proofreading show distinct single-strand mismatch patterns compared to samples that are deficient in only polymerase proofreading. We also define a single-strand damage signature for APOBEC3A. In the mitochondrial genome, our findings support a mutagenic mechanism occurring primarily during replication. As double-strand DNA mutations are only the end point of the mutation process, our approach to detect the initiating single-strand events at single-molecule resolution will enable studies of how mutations arise in a variety of contexts, especially in cancer and ageing.

Testosterone therapy in females is not associated with increased cardiovascular or breast cancer risk: a claims database analysis.

BACKGROUND: Testosterone therapy (TTh) has been shown to improve libido in women with sexual dysfunction, but its utilization has been limited due to concern for cardiovascular events and past studies reporting highly variable results. AIM: To assess the association of TTh in women with major adverse cardiac events (MACEs), including heart attack, stroke, or death, using a large database. METHODS: The TriNetX Diamond Network was queried from 2009 to 2022. Our study cohort included adult females with ≥3 systemic testosterone prescriptions within a year. Our control cohort excluded females with any testosterone prescriptions, polycystic ovary syndrome, or androgen excess. Both cohorts excluded females with prior heart failure, unstable angina, intersex surgery (female to male), personal history of sex reassignment, or gender identity disorders. Propensity matching between the cohorts was performed. A subanalysis by age was conducted (18-55 and >55 years). OUTCOMES: We evaluated the association of TTh to the following: MACE, upper or lower emboli or deep vein thrombosis (DVT), pulmonary embolism (PE), breast neoplasm, and hirsutism within 3 years of TTh. RESULTS: When compared with propensity-matched controls, adult females with TTh had a lower risk of MACE (risk ratio [RR], 0.64; 95% CI, 0.51-0.81), DVT (RR, 0.61; 95% CI, 0.42-0.90), PE (RR, 0.48; 95% CI, 0.28-0.82), and malignant breast neoplasm (RR, 0.48; 95% CI, 0.37-0.62). Similarly, females aged 18 to 55 years with TTh had a lower risk of MACE (RR, 0.49; 95% CI, 0.28-0.85) and DVT (RR, 0.48; 95% CI, 0.25-0.93) and a similar risk of malignant breast neoplasm (RR, 0.62; 95% CI, 0.34-1.12). Females aged ≥56 years with TTh had a similar risk of MACE (RR, 0.84; 95% CI, 0.64-1.10), DVT (RR, 0.82; 95% CI, 0.50-1.36), and PE (RR, 0.52; 95% CI, 0.26-1.05) and a significantly lower risk of malignant breast neoplasm (RR, 0.51; 95% CI, 0.38-0.68). Risk of hirsutism was consistently higher in those with TTh as compared with propensity-matched controls. CLINICAL IMPLICATIONS: Our results contribute to safety data on TTh, a therapy for sexual dysfunction in women. STRENGTHS AND LIMITATIONS: The TriNetX Diamond Network allows for significant generalizability but has insufficient information for some factors. CONCLUSIONS: We found a decreased risk of MACE among women with TTh as compared with matched controls and a similar risk of MACE in postmenopausal women while demonstrating a similar or significantly lower risk of breast cancer on age-based subanalysis.

Perioperative Plasma in Addition to Red Blood Cell Transfusions Is Associated With Increased Venous Thromboembolism Risk Postoperatively.

BACKGROUND: Perioperative red blood cell (RBC) transfusions increase venous thromboembolic (VTE) events. Although a previous study found that plasma resuscitation after trauma was associated with increased VTE, the risk associated with additional perioperative plasma is unknown. METHODS: A US claims and EHR database (TriNetX Diamond Network) was queried. We compared surgical patients who received perioperative plasma and RBC to patients who received perioperative RBC but not plasma. Subanalyses included (1) all surgeries (n = 48,580) and (2) cardiovascular surgeries (n = 38,918). Propensity score matching was performed for age at surgery, ethnicity, race, sex, overweight and obesity, type 2 diabetes, disorders of lipoprotein metabolism, essential hypertension, neoplasms, nicotine dependence, coagulopathies, sepsis, chronic kidney disease, liver disease, nonsteroidal anti-inflammatory analgesics, platelet aggregation inhibitors, anticoagulants, hemoglobin level, outpatient service utilization, and inpatient services; surgery type was included for "all surgeries" analyses. Outcomes included 30-day mortality, postoperative VTE, pulmonary embolism (PE), and disseminated intravascular coagulation (DIC). RESULTS: After matching the surgical cohorts, compared to only RBC, plasma + RBC was associated with higher risk of postoperative mortality (4.52% vs 3.32%, risk ratio [RR]: 1.36 [95% confidence interval, 1.24-1.49]), VTE (3.92% vs 2.70%, RR: 1.36 [1.24-1.49]), PE (1.94% vs 1.33%, RR: 1.46 [1.26-1.68]), and DIC (0.96% vs 0.35%, RR: 2.75 [2.15-3.53]). Among perioperative cardiovascular patients, adding plasma to RBC transfusion was associated with similar increased risk. CONCLUSIONS: When compared with perioperative RBC transfusion, adding plasma was associated with increased 30-day postoperative mortality, VTE, PE, and DIC risk among surgical and cardiovascular surgical patients. Reducing unnecessary plasma transfusion should be a focus of patient blood management to improve overall value in health care.