High Risk Research Articles

Optimizing Post-activation Performance Enhancement in Athletic Tasks: A Systematic Review with Meta-analysis for Prescription Variables and Research Methods.

Post-activation performance enhancement (PAPE) has demonstrated efficacy in acutely improving athletic performance. However, its distinction from general warm-up (GW) effects remains ambiguous, and experimental designs adopted in most PAPE studies exhibit important limitations. The aims of this work are to (i) examine the effects of research methodology on PAPE outcomes, (ii) explore PAPE outcomes in relation to comparison methods, performance measures, GW comprehensiveness, recovery duration, participants' characteristics, conditioning activity (CA) parameters, and (iii) make recommendations for future PAPE experimental designs on the basis of the results of the meta-analysis. Four databases were searched for peer-reviewed English-language literature. Risk of bias was assessed using a modified Cochrane Collaboration's tool and PEDro scale. PAPE groups were compared with control groups, pre-conditioning activity (pre-CA) performances were compared with post-conditioning activity (post-CA) performances throughout a verification test in PAPE groups, and control groups were compared before and after the "rest" period using a three-level meta-analysis. Further analyses, including subgroup analysis and both linear and nonlinear meta-regression methods, were used to explore the effect of different moderating factors on PAPE magnitude. A subgroup analysis of GW comprehensiveness was conducted using four classification methods. One method classified GW as non-comprehensive (stretching or jogging only), partially comprehensive (stretching, jogging, and low-intensity self-weighted dynamic exercises), and comprehensive (adding maximal or near-maximal intensity CAs to a partially comprehensive GW). The other three classifications were adjusted according to the type and number of GW exercises. Certainty of evidence was assessed using the GRADE approach. The final analysis included 62 PAPE studies (1039 participants, male: n = 857, female: n = 182) with a high risk of bias and low certainty of pooled evidence. A trivial PAPE effect was observed from pre- to post-CA (effect size [ES] = 0.12, 95% CI [0.06 to 0.19], prediction intervals [PI] = - 0.29 to 0.54); a small PAPE effect was observed when compared with a control group (ES = 0.30, 95% CI [0.20 to 0.40], PI [- 0.38 to 0.97]). The slightly greater effect against control resulted from a small decrease in performance in control groups (ES = - 0.08, 95% CI [- 0.13 to - 0.03], PI [- 0.30 to 0.14]), but there was no relationship with between PAPE recovery time (β = - 0.005, p = 0.149). Subgroup analyses showed that PAPE magnitude was greater for non-comprehensive GWs (ES = 0.16) than comprehensive (ES = 0.01) and partially comprehensive GWs (ES = 0.11). In contrast, the control group showed a decline in performance after comprehensive GW (ES = - 0.20). An inverted U-shaped PAPE was noted as a function of recovery time. In some cases, PAPE appeared to manifest at < 1min post CA. Additionally, participants with longer training experience (ES = 0.36) and higher training levels (ES = 0.38) had larger PAPE magnitudes. PAPE effect was higher in females (ES = 0.51) than males (ES = 0.32) and mixed groups (ES = 0.16) but did not reach a significant difference (p > 0.05). Plyometric exercise (ES = 0.42) induced greater PAPE amplitude than traditional resistance exercise (ES = 0.23), maximal isometric voluntary contraction (ES = 0.31) and other CA types (ES = 0.24). Although the overall pooled results for both PAPE pre- versus post-CA and PAPE versus control group comparisons showed significant improvement, the wider and past-zero prediction intervals indicate that future studies are still likely to produce negative results. The comprehensiveness of the GW, the time between GW and the pre-CA test, participant sex, training level, training experience, type of CA, number of CA sets, and recovery time after CA all influence the PAPE magnitude. The PAPE magnitude was trivial after comprehensive GW, but it was greater in studies with a control group (i.e., no CA) because performance decreased over the control period, inflating the PAPE effect. Finally, two theoretical models of PAPE experimental design and suggestions for methodological issues are subsequently presented. Future studies can build on this to further explore the effects of PAPE. The original protocol was prospectively registered (osf.io/v7sbt) with the Open Science Framework.

Total marrow irradiation as part of autologous stem cell transplantation for patients with multiple myeloma.

The efficacy and safety of total marrow irradiation (TMI) plus a reduced dose of melphalan as autologous stem cell transplantation (ASCT) preconditioning for multiple myeloma (MM) patients were evaluated. The 11 patients with MM had a median age of 57 (range: 46-75) years; six of them were at standard risk and five of them were at high risk based on the Mayo Stratification of Myeloma and Risk-adapted Therapy (mSMART) standard risk factors. Before ASCT, three patients achieved stringent complete response (sCR), two patients achieved complete remission (CR), and the rest of the patients had either partial response (PR) or progressive disease. Most of the 11 patients were pretreated with melphalan 120-140 mg/m2 and TMI 12Gy. The intravenous infusion median mononuclear cell count (MNC) was 8.13 (4.16-11.84) × 108/kg, and the median CD34+ count was 4.74 (2.51-21.98) × 106/kg. The minimal residual disease (MRD) in the grafts as determined by flow cytometry (FCM) and fluorescence in situ hybridization (FISH) were negative in 10 patients but positive in the progressive patient. All patients stopped maintenance therapy after transplantation, and further observation focused on the efficacy and tolerability of the transplantation. The neutropenic and thrombocytopenia durations were 11 (7-28) and 14 (8-70) days, respectively. The primary acute non-hematological toxicities were mild oral and gastrointestinal mucositis; there were no transplant-related deaths or serious complications. Of the eight patients who did not achieve sCR before transplantation, seven converted to sCR and one converted to VGPR after transplantation. The median follow-up period was 24 (10-57.5) months. Only one patient relapsed, and the progression-free survival (PFS) was 90.9%, while the overall survival (OS) was 100%. Our preliminary results suggest that melphalan 120-140 mg/m2 plus TMI 12Gy/6f as a conditioning regimen is safe and efficient for patients with MM.

Association of Geriatric Nutritional Risk Index Scores with Outcomes in Patients Undergoing Maintenance Hemodialysis.

Aims/Background The Geriatric Nutritional Risk Index (GNRI) is an effective tool for identifying malnutrition, and helps monitor the prognosis of patients undergoing maintenance hemodialysis. However, the association between the GNRI and cardiovascular or all-cause mortality in hemodialysis patients remains unclear. Therefore, this study investigated the correlation of the GNRI with all-cause and cardiovascular mortality in patients undergoing maintenance hemodialysis. Methods This study included 402 incident hemodialysis patients. Based on the first-dialysis GNRI quartile, the patients were divided into four groups: N1 (GNRI ≤85.04), N2 (GNRI 85.05-91.04), N3 (91.05-96.49), N4 (GNRI ≥96.5) groups. The risk of all-cause and cardiovascular mortality among the different GNRI groups was compared using the Kaplan-Meier survival curve analysis through log-rank tests. Furthermore, Cox regression analysis was used to assess the association between the GNRI groups and all-cause mortality. Additionally, the predictive capability of the GNRI groups on the prognosis was evaluated by employing receiver operating characteristic (ROC) curve analysis. Results Patients in the N1 group exhibited a significantly higher risk of all-cause mortality (p < 0.001) and cardiovascular mortality (p = 0.004) compared to the other groups. ROC curve analysis revealed that GNRI, age, and serum creatinine had moderate predictive value for mortality, with GNRI indicating an area under the curve (AUC) of 0.605 for all-cause mortality and 0.565 for cardiovascular mortality. Moreover, the N2 and N3 groups had a significantly reduced risk of cardiovascular mortality compared to the N1 group. Conclusion A lower GNRI is closely associated with a higher risk of all-cause and cardiovascular mortality in hemodialysis patients.

Incidence rates of tuberculosis and inflammatory bowel disease in patients with ankylosing spondylitis treated with biologics in Korea.

To describe the incidence rates of inflammatory bowel disease (IBD) and tuberculosis (TB) in Korean patients with ankylosing spondylitis receiving biologics. Data from a Korean claims database between 2010 and 2021 was used to calculate crude incidence rates of TB and IBD using number of events and total patient-years (PYs). Overall, 43 643 and 43 396 patients were included in TB and IBD cohorts. Exposure adjusted incidence rates (EAIRs) of TB for non-exposure, tumor necrosis factor inhibitors (TNFis), and interleukin-17 inhibitors (IL-17is) were 0.14, 0.25, and 0.12 and of IBD were 0.18, 0.19, and 0.44 per 100 PYs, respectively. Incidence rates during biologic disease-modifying antirheumatic drugs (bDMARDs) non-exposure, adalimumab, etanercept, golimumab, infliximab, secukinumab and ixekizumab exposures for TB were 13.96, 27.79, 14.28, 21.19, 33.62, 12.74, and 0.00 and for IBD were 18.29, 19.98, 22.41, 18.85, 15.73, 44.99, and 0.00 per 10 000 PYs, respectively. Compared with bDMARDs non-exposure, adalimumab, golimumab, and infliximab exposures were associated with a significantly higher risk of TB. Etanercept and secukinumab exposure showed no significant increase in risk of TB. Compared with bDMARDs non-exposure, exposure to biologics did not show a significant difference in risk of IBD. EAIRs of TB and IBD with use of IL-17is in patients with AS were within anticipated low range. IL-17is had numerically lower incidence of TB, and numerically higher incidence of IBD compared with TNFis. Notably, secukinumab showed no increased risk of TB compared with bDMARDs non-exposure. Neither TNFis nor IL-17is showed increased risk of IBD compared with bDMARDs non-exposure.

Impact of delirium on post-discharge mortality in coronary care unit patients: A retrospective cohort study.

Coronary care unit (CCU) patients surviving to discharge still face significant mortality. Delirium is common in CCU patients and has been associated with poorer CCU and in-hospital outcomes. To assess the association between delirium and mortality after hospital discharge in CCU survivors. This was a retrospective observational study that included patients admitted to CCU. All data were extracted from the Medical Information Mart for Intensive Care IV database. The exposure was delirium during CCU stay. The primary outcome was mortality 180 days after hospital discharge. Secondary outcomes included post-hospital discharge mortality at 90 days, length of CCU and hospital stays, and hospital discharge disposition. Of the 3609 CCU patients included, 891 were considered delirium-positive during their CCU stay. Delirium was associated with an increased risk of mortality at 180 days after hospital discharge (adjusted hazard ratio [HR], 1.33; 95% confidence interval (CI), 1.08-1.64). Similar results were observed for 90-day post-discharge mortality (adjusted HR,1.43; 95% CI, 1.13-1.83). CCU patients who experienced delirium had longer stays in both the CCU and hospital (adjusted β, 2.11; 95% CI, 1.79-2.43 and 3.87; 95% CI, 3.06-4.69, respectively). They were also more likely to require nursing care after hospital discharge (adjusted odds ratio [OR], 1.65; 95% CI, 1.22-2.22). Delirium during CCU stay was associated with an increased risk of all-cause mortality up to 180 days in CCU patients who survived hospital discharge. Delirium places CCU patients at a higher risk of post-discharge mortality and increased health care resource requirements. Given the high prevalence of delirium in CCU patients and its significantly deleterious impact on both short-term and long-term post-discharge mortality, nurses and physicians should enhance the post-discharge management of patients who experience delirium in order to improve prognosis. This also highlights the importance of preventing and managing delirium during hospitalization.

Socio-economic inequalities in second primary cancer incidence: A competing risks analysis of women with breast cancer in England between 2000 and 2018.

We aimed to investigate socio-economic inequalities in second primary cancer (SPC) incidence among breast cancer survivors. Using Data from cancer registries in England, we included all women diagnosed with a first primary breast cancer (PBC) between 2000 and 2018 and aged between 18 and 99 years and followed them up from 6 months after the PBC diagnosis until a SPC event, death, or right censoring, whichever came first. We used flexible parametric survival models adjusting for age and year of PBC diagnosis, ethnicity, PBC tumour stage, comorbidity, and PBC treatments to model the cause-specific hazards of SPC incidence and death according to income deprivation, and then estimated standardised cumulative incidences of SPC by deprivation, taking death as the competing event. Multiple imputation was performed to account for missing data. Among 649,905 included women, 47,399 SPCs and 171,223 deaths occurred during 4,269,042 person-years of follow-up. Income deprivation was consistently associated with an increased rate of SPC incidence (cause-specific hazard ratio for the most vs. least deprived quintile: 1.29; 95% CI: 1.25, 1.33) and of death (1.36; 1.34, 1.38), translating into an absolute risk difference (the most vs. least deprived quintile) of 1.3% (95% CI: 1.0, 1.5) for SPC incidence and 4.9% (95% CI: 4.6, 5.1) for death at 10 years. Women with PBC from deprived areas in England faced a substantially higher risk of SPC than their counterparts. Future research is warranted to understand mechanisms for observed inequalities to inform strategies to monitor, prevent, and identify SPC in women with PBC.

Immune Cell Characteristics and Infections Associated with Chronic Obstructive Pulmonary Disease (COPD), Asthma, and Interstitial Lung Disease (ILD): A Mendelian Randomization Studies.

Aims/Background Epidemiological studies indicate that the involvement of the immune system in the pathogenesis of infections associated with chronic obstructive pulmonary disease (COPD), asthma, and interstitial lung disease (ILD) remains unclear. This study aims to assess the potential causal link between infections associated with COPD, asthma, or ILD and immune system function. Methods We conducted a two-sample Mendelian randomization analysis using publicly available genome-wide association study (GWAS) datasets. The causal relationship between immune cell signaling and susceptibility to infections related to COPD, asthma, and ILD was evaluated using inverse variance weighting (IVW), Mendelian randomization (MR)-Egger regression, weighted median, weighted mode, and simple mode approaches. To concurrently assess the causal impact of immune cell signaling on infection susceptibility associated with COPD, asthma, and ILD, a reverse Mendelian randomization analysis was also conducted. Results Genetic predisposition to elevated counts of circulating blood cells and their subpopulations demonstrated significant causal associations with a higher risk of COPD/asthma/ILD-related infections, as determined by IVW analysis. Specifically, genetically predicted increases in white blood cell count (odds ratio (OR) 1.08 [95% confidence interval (CI): 1.04-1.11], p < 0.00001), neutrophil count (OR: 1.06 [95% CI: 1.02-1.10], p = 0.00190), lymphocyte count (OR: 1.04 [95% CI: 1.01-1.07], p = 0.01515), monocyte count (OR: 1.03 [95% CI: 1.01-1.06], p = 0.00440), and eosinophil count (OR: 1.07 [95% CI: 1.04-1.10], p = 0.00001) were causally correlated with an increased risk of these respiratory infections. Notably, four immunophenotypes were significantly associated with the risk of COPD/asthma/ILD-related infections: Human Leukocyte Antigen (HLA) DR+ NK% NK (OR: 0.98 [95% CI: 0.97-0.99], p = 0.0004), CD66b on CD66b++ myeloid cell (OR: 0.98 [95% CI: 0.97-0.99], p = 0.0007), HLA DR on CD14+ monocyte (OR: 1.03 [95% CI: 1.01-1.04], p = 0.0002), and HLA DR on CD33- HLA DR+ (OR: 1.03 [95% CI: 1.02-1.05], p < 0.00001). The causal effect of COPD/asthma/ILD-related infections on Immunoglobulin D (IgD) expression in IgD+ CD38br and transitional B cells was estimated to be 0.64 (95% CI: 0.49-0.83, p = 0.00091) and 0.70 (95% CI: 0.54-0.91, p = 0.00727), respectively. Additionally, COPD/asthma/ILD-related infections demonstrated a significant causal effect on several B cell and T cell subpopulations: IgD+ CD38- % B cells, IgD+ CD38- AC, CD4+ CD8dim AC, IgD+ CD38- % lymphocyte, and TD CD4+ AC, with the OR 1.54 (95% CI: 1.19-2.00, p = 0.00113), 1.56 (95% CI: 1.16-2.10, p = 0.00340), 1.60 (95% CI: 1.15-2.22, p = 0.00478), 1.47 (95% CI: 1.12-1.92, p = 0.00483) and 1.63 (95% CI: 1.14-2.34, p = 0.00725), respectively. Conclusion Our study reveals a causal association between altered circulating blood cell counts and specific immunophenotypes with the susceptibility to respiratory infections related to COPD, asthma, and ILD.

Diabetes Risk After Treatment for Childhood and Young Adult Cancer.

Diabetes is a potential late consequence of childhood and young adult cancer (CYAC) treatment. Causative treatments associated with diabetes have been identified in retrospective cohort studies but have not been validated in population-based cohorts. Our aim was to define the extent of diabetes risk and explore contributory factors for its development in survivors of CYAC in the United Kingdom. Cancer registration data (n = 4,238) were linked to electronic health care databases to identify cases of diabetes through clinical coding or HbA1c values. Total effect of prespecified treatment exposures on diabetes risk was estimated using flexible parametric modeling and standardized cause-specific cumulative incidence functions (CIFs). After median follow-up of 14.4 years, 163 individuals (3.8%) were identified with diabetes. Total body irradiation (TBI) increases diabetes risk over time, with a 40-year CIF reaching 21.0% (95% CI 13.8-31.9) compared with 8.4% (95% CI 6.1-11.5) without TBI. Survivors treated with corticosteroids had a 7.7% increased risk at 40 years after cancer diagnosis. Hematopoietic stem cell transplant (HSCT) survivors had markedly higher risk, with a 40-year CIF of 19.6% (95% CI 13.4-28.6) versus 8.2% (95% CI 6.0-11.3) for patients who had not undergone HSCT. Among patients who received allogeneic HSCT, the 40-year CIF of diabetes was 25.7% (95% CI 17.4-38.0), compared with 7.9% (95% CI 3.3-19.1) in patients who received autologous transplants. This evaluation of a hospital-based cohort of patients with CYAC identifies these patients' increased long-term risk of developing diabetes and how this varies temporally according to treatment modalities. Notable contrasts in risk by treatment were detected as early as 10 years after cancer diagnosis. Findings should inform the development of risk-stratified evidence-based screening.

A cohort study on the association between blood pressure trajectories and variability in adolescence and subsequent target organ damage

Objective: To investigate the relationship between blood pressure trajectories and blood pressure variability with the risk of target organ damage in Chinese population from childhood to middle age. Methods: This study is a population-based, long-term follow-up cohort study. Participants who had their blood pressure measured at least 5 times in the Hanzhong Adolescent hypertension cohort from 1987 to 2023 were included in this study. Group-based trajectory modeling was used to identify different systolic and diastolic blood pressure trajectories, and the subjects were divided into low-increasing group, moderate-increasing group and high-increasing group according to blood pressure trajectories. Blood pressure variability was assessed using standard deviation (SD), variability independent of the mean (VIM), and average real variability (ARV). Target organ damage was evaluated during the final follow-up in 2023 (middle age). Logistic regression models were used to analyze the relationship between blood pressure trajectories and blood pressure variability with the risk of target organ damage. Results: A total of 2 447 subjects were included, with a median age of 48 years, of whom 1 373 were male (56.1%). Based on systolic blood pressure, 868 were in the low-increasing group, 1 238 in the moderate-increasing group, and 341 in the high-increasing group. For diastolic blood pressure, the distribution was 894, 1 263 and 290, respectively. Compared with the low-increasing group of systolic blood pressure, the moderate-increasing group (arteriosclerosis: OR=4.14, 95%CI 2.96-5.79; proteinuria: OR=2.06, 95%CI 1.38-3.07; left ventricular hypertrophy: OR=1.68, 95%CI 1.00-2.82) and high-increasing group (arterial stiffness: OR=15.44, 95%CI 10.14-23.50; proteinuria: OR=5.80, 95%CI 3.63-9.29; left ventricular hypertrophy: OR=2.93, 95%CI 1.55-5.53) had a higher risk of target organ damage (all P<0.005). The moderate-increasing group of diastolic blood pressure had a higher incidence of arterial stiffness (OR=3.72, 95%CI 2.69-5.12) and proteinuria (OR=1.67, 95%CI 1.15-2.42) than the low-increasing group (all P<0.005), while the high-increasing group had a significantly higher risk of all type of target organ damage compared to the low-increasing group (arterial stiffness: OR=10.84, 95%CI 7.08-16.61; proteinuria: OR=3.72, 95%CI 2.31-5.99; left ventricular hypertrophy: OR=2.38, 95%CI 1.23-4.59; all P<0.005). Additionally, higher systolic blood pressure variability was associated with an increased incidence of arterial stiffness (SD: OR=2.25, 95%CI 1.96-2.57; VIM: OR=1.64, 95%CI 1.45-1.86; ARV: OR=1.70, 95%CI 1.50-1.93) and proteinuria (SD: OR=1.65, 95%CI 1.44-1.89; VIM: OR=1.41, 95%CI 1.22-1.63; ARV: OR=1.45, 95%CI 1.26-1.67; all P<0.005). The results for diastolic blood pressure variability indicators were similar to those for systolic blood pressure. Conclusion: Early-life blood pressure trajectories are predictive of target organ damage risk in middle age. Higher blood pressure variability is related to an increased risk of arterial stiffness and proteinuria, but was less associated with left ventricular hypertrophy. Focusing on the risk of high blood pressure early in life can help prevent the occurrence of target organ damage in middle age.

Blood management protocol for baseline anemic patients undergoing hip arthroplasty.

Patients undergoing total hip arthroplasty (THA) with preoperative anemia are at higher risk for transfusion. Blood-conserving interventions can reduce perioperative transfusions. This retrospective study evaluates the efficacy and safety of a patient blood management (PBM) protocol in elective primary THA patients with preoperative anemia. We analyzed data from a prospectively collected database of THAs performed consecutively from January 2013 to October 2023. The patients were grouped based on baseline hemoglobin (Hb) levels, as follows: <12g/dL (group 1) and ≥ 12g/dL (group 2). The PBM protocol included optimized preoperative epoetin (EPO) for Hb < 11g/dL, bleeding reduction measures, and restrictive transfusion thresholds. Blood loss was measured using a bleeding index (BI-7), accounting for Hb decrease from admission to the 7th postoperative day and total transfused units. Multiple linear regression was used to assess the differences in BI-7. Of the 1,442 patients, 104 (7%) had Hb < 12g/dL (group 1). Among these, 46 (45%) received EPO, with none requiring transfusion in the first week. The mean adjusted BI-7 was 2.3g/dL (95% CI, 2.1 to 2.6) in group 1 and 2.7g/dL (95% CI, 2.6 to 2.7) in group 2, showing a significant difference (-0.4g/dL; 95% CI, -0.6 to -0.1; p < 0.001). THA patients with baseline Hb < 12g/dL had a zero-transfusion rate and significantly lower blood loss than those with Hb ≥ 12g/dL. Optimizing preoperative Hb levels above 12 g/dL is not necessary for patients undergoing standard THA. Optimizing preoperative Hb may not be necessary for patients with baseline anemia due to their low blood loss. The PBM protocol was effective in conserving blood, time, and resources, offering a viable alternative for blood conservation in elective hip arthroplasty.

Ionized calcium and PTH as predictors of hypoparathyroidism following total thyroidectomy.

Post-surgical hypoparathyroidism (POSH) is a common complication after total thyroidectomy. This study aims to assess the accuracy of serum and ionized calcium and PTH levels on the first postoperative day (POD-1) to predict postoperative hypocalcemia (PoHC), transient hypoparathyroidism (THPT), and permanent hypoparathyroidism (PtHPT). Biochemical parameters and clinical variables were retrospectively analyzed in 200 patients. The optimal cut-off points were determined using ROC curve analysis. Results were correlated with analytical and clinical variables and patient outcomes. PoHC incidence in POD-1 was 46%; THPT and PtHPT were 37 and 9%, respectively. Ionized calcium < 4.43mg/dL on POD-1 predicted PoHC (AUC = 0.9) better than PTH and serum calcium. PTH < 8.06pg/mL on POD-1 predicted PtHPT (AUC = 0.797). Multivariate analysis identified PTH < 21.2pg/mL, ionized calcium < 4.43mg/dL, and serum calcium < 8.76mg/dL on POD-1 as significant PoHC risk factors. Ionized calcium on POD-1 predicts PoHC accurately, while serum PTH indicates higher risk for PtHPT.

Breast MRI to Screen Women With Extremely Dense Breasts.

Women with extremely dense breasts are at a higher risk of breast cancer, and the sensitivity of mammography in this group is reduced due to the masking effect of overlapping tissue. This review examines supplemental screening methods to improve detection in this population, with a focus on MRI. Morphologic techniques offer limited benefits, digital breast tomosynthesis (DBT) shows inconsistent results, and ultrasound (US), while improving cancer detection rates (CDR), results in a higher rate of false positives. Functional imaging techniques show better performance, molecular breast imaging increases CDR but is limited in availability, and contrast-enhanced mammography is promising, with good results and as an accessible technique, but requires further validation. MRI, with sensitivity ranging from 81% to 100%, is the most supported modality. Despite strong evidence for MRI in this population, high costs, use of contrast, and longer scan times hinder widespread use. Abbreviated MRI protocols aim to overcome these barriers by reducing costs and scan duration. As personalized screening becomes a future focus, MRI remains the most effective option for women with extremely dense breasts. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 5.

Distribution of pharmaceuticals in marine surface sediment and macroalgae (ulvophyceae) around Mombasa peri-urban creeks and Gazi Bay, Kenya.

Pollution in marine creeks has been increasing due to anthropogenic activities and has been a global concern. Limited research has been conducted on pharmaceuticals in marine sediment and macroalgae in African countries. In the present study, the levels of pharmaceuticals were assessed in surface sediment and different species of macroalgae (ulvophyceae; Cladophora sudanensis, Chaetomorpha crassa, Chaetomorpha indica, Enteromorpha kylinii, Ulva reticulate, Ulva lactuca and Cladophora sibugae) in Mombasa peri-urban creeks (Tudor, Makupa and Mtwapa creek) and Gazi bay during dry and wet seasons. The concentration of pharmaceuticals in the surface sediment during dry and wet seasons ranged between 0.04-686.8ng/g and 0.01-2580.6ng/g, respectively. The highest concentration of pharmaceuticals was observed in Tudor creek in dry and wet seasons, with a sum concentration of ∑1013ng/g and ∑3111ng/g, respectively. Gazi Bay was used as a reference environment for this study, and pharmaceuticals were detected in dry and wet seasons with a concentration of 0.10-686.8ng/g and 0.18-93.5ng/g, respectively. There was no seasonal variation in the pharmaceutical concentration during the dry and wet seasons. For macroalgae of ulvophyceae species, pharmaceutical concentration ranged below the detection limit (DL)-11059ng/g. Compared to surface sediment, macroalgae showed a high concentration of pharmaceuticals in Tudor, Makupa and Mtwapa creeks. Tetracycline was higher in sediment and macroalgae in all the creeks than other pharmaceutical compounds. A high concentration of pharmaceuticals confirms sewage effluent into the marine environment of Mombasa peri-urban creek. Pharmaceuticals (acetaminophen, sulfamethoxazole, trimethoprim, carbamazepine and nevirapine) in sediment posed a medium (- 1 < Log10 RQ < 0) to higher risk (Log10 RQ > 0) to algae, invertebrates and fish in the dry and wet seasons. There is a need to sensitise the residents of coastal cities on the impact of sewage effluent into the marine environment and enact strict measures to limit the discharge of sewage effluents containing these contaminants into the marine environment. Nevertheless, it is recommended to conduct further research on the distribution of pharmaceuticals in the marine environment and the long-term combined impacts of these substances of these compounds on marine biota.

Impact of maternal overweight/obesity and high fasting plasma glucose on adverse perinatal outcomes in early gestational diabetes mellitus.

To elucidate risk factors associated with adverse perinatal outcomes in early-gestational diabetes mellitus (GDM). A dataset of 385 early-GDM cases from a prospective cohort was analyzed. Early-GDM was diagnosed if one or more of the following criteria were met: fasting plasma glucose (PG) levels of 92-125 mg/dL, 1-h PG levels ≥180 mg/dL, and 2-h PG levels ≥153 mg/dL during a 75-g oral glucose tolerance test before 20 weeks of gestation. Multivariate analysis was used to examine associations between candidate risk factors and a composite outcome of maternal and neonatal adverse events. Pre-pregnancy overweight/obesity (pre-pregnancy body mass index [BMI] ≥25.0 kg/m2) was significantly associated with a higher risk of the composite outcome compared with normal weight (pre-pregnancy BMI of 18.5-24.9 kg/m2), an adjusted risk ratio (aRR) of 1.44 (95% confidence interval [CI]: 1.08-1.93), and an adjusted risk difference (aRD) of 13.6% (95% CI: 2.6-24.6%). Compared with fasting PG levels below 92 mg/dL, levels between 95 and 125 mg/dL were associated with a significantly higher risk of the composite outcome, with an aRR and aRD of 1.42 (95% CI: 1.01-1.99) and 12.9% (95% CI: 0.3-25.5%), respectively. Early-GDM, combined with pre-pregnancy overweight/obesity and/or fasting PG levels of 95-125 mg/dL, is associated with a higher risk of adverse perinatal outcomes and should be prioritized for intervention.

Human health risk assessment by exposure to contaminants from an urban reservoir: a pilot study in the Madin Dam (México).

Water contamination greatly impacts human health. The Metropolitan Area of the Valley of Mexico (MAVM) is one of the most densely inhabited and polluted places globally, with a significant problem being the rising water demand. The research aims to assess the impact of metals such as iron, aluminum, lead, cadmium, and total chromium, among others, in the water of the Madin Dam, a key reservoir in the area's water supply. The assessment concentrated on individuals who were in good health and had been exposed to these pollutants. It analyzed factors such as levels of oxidized proteins; changes in the function of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase); and their genetic expression, the occurrence of micronuclei, and the amount of DNA methylation. The findings were linked to the metals present in the MAVM drinking water, and the risk was evaluated. The research included four groups: two associated with the Madin Dam, consisting of persons living nearby or using water from the reservoir, and two acting as a control. The study highlighted a significant link between long-term exposure to pollutants in drinking water and elevated levels of oxidized proteins, increased micronuclei frequency, changes in antioxidant enzyme activity and gene expression, and a higher percentage of 5-methylcytosine. The risk assessment showed that people who use drinking water and/or consume fish from Madin Dam have a potential higher risk associated with metal contamination.

Palbociclib Is Safe for Breast Cancer Patients With Mild Hepatic Impairment: A Multicenter Retrospective Study Using Real-World Data.

The liver is crucial for metabolizing the anticancer drug palbociclib, but limited information is available on the impact of hepatic impairment on its toxicity and efficacy, with no real-world data available. This study aims to evaluate how hepatic impairment affects hematological toxicity and progression-free survival (PFS) of palbociclib in advanced hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer, using the National Cancer Institute scoring system, in a large real-world dataset. This multicenter retrospective observational study included female patients treated with palbociclib between August 2017 and February 2024. Regression analysis was used to compare the risk of developing grade 3/4 hematological toxicity and PFS between patients with normal and mild impaired liver function. In total, 478 female patients were included. Patients with mild hepatic impairment (n = 205) did not have an increased risk of developing grade 3/4 neutropenia compared with patients with normal hepatic function (n = 273) (hazard ratio (HR) = 1.11; 95% CI 0.83-1.47). In addition, the PFS was not significantly different between both groups (HR = 1.15; 95% CI 0.93-1.42). In real-world settings, patients with mild hepatic impairment do not have a higher risk of developing palbociclib-induced neutropenia or disease progression than patients with normal hepatic function. These findings can guide clinicians when treating breast cancer patients with mild hepatic impairment.

Effects of Investments From the Centers for Disease Control and Prevention's COVID-19 Health Disparities Grant on Health Departments' Capacity to Address Public Health Emergencies.

The COVID-19 pandemic magnified long-standing health disparities, showing that certain populations are at higher risk for effects of public health emergencies than others. The pandemic response also put demands on the nation's health departments and stretched their limited resources. In 2021, the Centers for Disease Control and Prevention launched the National Initiative to Address COVID-19 Health Disparities Among Populations at High-Risk and Underserved, Including Racial and Ethnic Minority Populations and Rural Communities (hereinafter, COVID-19 Health Disparities Grant) to reduce COVID-19 health disparities and advance health equity. Health departments in all 50 states, 50 localities, 5 territories, and 3 freely associated states were recipients of approximately $2.25 billion. This study explored the extent to which investments from the COVID-19 Health Disparities Grant, through the allocation of funds across 5 strategies, correspond to reported changes in recipient health departments' capacity to address the COVID-19 public health emergency and future emergencies as measured in the Health Department and Jurisdiction Capacity Survey in 2023. The survey measured capacity along 4 domains: workforce and human resources, interorganizational relationships, data and informational resources, and governance and planning. In total, 70 of 75 recipients who responded to the survey reported that they began with low capacity in at least 1 capacity domain and advanced their capacity during grant implementation. This study demonstrated the reported value of investments in health departments to build capacity and infrastructure to address health disparities and advance health equity to respond to future public health emergencies.

Alkaline phosphatase of late pregnancy promotes the prediction of adverse birth outcomes.

Adverse birth outcomes (ABO), such as preterm birth (PTB), small and large for gestational age (SGA/LGA), can compromise both the short- and long-term health of mothers and their foetuses. The purpose of this observational study was to investigate the association between maternal serum alkaline phosphatase (ALP) levels in late pregnancy and the risk of ABO, and to evaluate its predictive value of maternal ALP levels for ABO in women with singleton pregnancies. A total of 11 853 consecutive pregnant women underwent hepatic and renal function tests, lipid profile assessments, ALP and high-sensitivity C-reactive protein levels measurements upon admission for labour. Their clinical perinatal parameters and outcomes were also analysed. The prevalence of PTB, SGA, and LGA in this study was 7.2% (n = 849), 8.9% (n = 1053), and 15.6% (n = 1844), respectively. With increasing quartiles of maternal serum ALP levels, the foetal gestational age increased by 0.58 weeks (95% confidence interval (CI) = 0.50-0.66), 0.78 weeks (95% CI = 0.70-0.86), and 0.98 weeks (95% CI = 0.90-1.06), respectively, and the birth weight increased by 62.91 g (95% CI = 43.96-81.86), 91.54 g (95% CI = 72.41-110.67), and 117.92 g (95% CI = 98.18-137.67), respectively. Compared to women in the bottom quartile of ALP, those in the top quartile had a lower risk of PTB (adjusted odds ratio (OR) = 0.14; 95% CI = 0.11-0.18), a lower risk of SGA (adjusted OR = 0.65; 95% CI = 0.53-0.80), and a higher risk of LGA (adjusted OR = 1.92; 95% CI = 1.62-2.28). Sensitivity analyses conducted among individuals without advanced maternal age, obesity, multiparity, pregnancy complications, and PTB (for SGA/LGA) validated the consistency of these results. More importantly, adding ALP to the established model significantly increased the area under the curve (AUC) for predicting adverse birth outcomes: for PTB, the AUC increased from 0.761 to 0.809 (P < 0.001); for SGA, it increased from 0.754 to 0.759 (P = 0.014); and for LGA, it increased from 0.750 to 0.755 (P < 0.001). Maternal serum ALP levels in late pregnancy are significantly associated with the risk of ABO. When combined with clinical characteristics and routine laboratory results, ALP has incremental predictive value for ABO, particularly for PTB.

Lipoprotein(a) Atherosclerotic Cardiovascular Disease Risk Score Development and Prediction in Primary Prevention From Real-World Data.

Lp(a; Lipoprotein[a]) is a predictor of atherosclerotic cardiovascular disease (ASCVD); however, there are few algorithms incorporating Lp(a), especially from real-world settings. We developed an electronic health record (EHR)-based risk prediction algorithm including Lp(a). Utilizing a large EHR database, we categorized Lp(a) cut points at 25, 50, and 75 mg/dL and constructed 10-year ASCVD risk prediction models incorporating Lp(a), with external validation in a pooled cohort of 4 US prospective studies. Net reclassification improvement was determined among borderline-intermediate risk patients. We included 5902 patients aged ≥18 years (mean age 48.7±16.7 years, 51.2% women, and 7.7% Black). Our EHR model included Lp(a), age, sex, Black race/ethnicity, systolic blood pressure, total and high-density lipoprotein cholesterol, diabetes, smoking, and hypertension medication. Over a mean follow-up of 6.8 years, ASCVD event rates (per 1000 people-years) ranged from 8.7 to 16.7 across Lp(a) groups. A 25 mg/dL increment in Lp(a) was associated with an adjusted hazard ratio of 1.23 (95% CI, 1.10-1.37) for composite ASCVD. Those with Lp(a) ≥75 mg/dL had an 88% higher risk of ASCVD (hazard ratio, 1.88 [95% CI, 1.30-2.70]) and more than double the risk of incident stroke (hazard ratio, 2.55 [95% CI, 1.54-4.23]). C-statistics for our EHR and EHR+Lp(a) models in our EHR training data set were 0.7475 and 0.7556, respectively, with external validation in our pooled cohort (n=21 864) of 0.7350 and 0.7368, respectively. Among those at borderline/intermediate risk, the net reclassification improvement was 21.3%. We show the feasibility of developing an improved ASCVD risk prediction model incorporating Lp(a) based on a real-world adult clinic population. The inclusion of Lp(a) in ASCVD prediction models can reclassify risk in patients who may benefit from more intensified ASCVD prevention efforts.

Utility of loop diuretics as a marker of risk in clinical trials of heart failure with preserved ejection fraction: Analysis from the Swedish Heart Failure Registry.

It is common in heart failure (HF) trials, especially in HF with preserved (HFpEF) and mildly reduced ejection fraction (HFmrEF), to select for increased risk of outcomes ('enrichment'). We investigated the association between loop diuretic use and common trial outcomes. Patients in the Swedish HF Registry with HFmrEF and HFpEF were divided into three groups: no loop diuretic use, 1-40 mg furosemide equivalent, and >40 mg. Outcomes were assessed for all patients and high risk for exacerbation patients (previous HF hospitalization [HFH] or N-terminal pro-B-type natriuretic peptide ≥300 ng/L). Among 25 986 patients, 41.3% were not taking loop diuretics, 33.5% had 1-40 mg, and 25.2% had >40 mg; 80.7% were at high risk. With increasing diuretic dose, the crude risk of all outcomes increased in both analysis groups. Event rates for cardiovascular death (CVD)/HFH were as follows for total: no loop diuretic: 6, dose 1-40 mg: 17, dose >40 mg: 34 and as follows for high risk: no loop diuretic: 8, dose 1-40 mg: 19, dose >40 mg: 36. Hazard ratios (HRs) for CVD/HFH with no loop diuretic as reference for the total population were: 1-40 mg HR 2.59, >40 mg HR 4.91 (all p < 0.001), and for high risk were: 1-40 mg HR 2.21, >40 mg HR 4.05 (all p < 0.001). In HFpEF and HFmrEF, loop diuretics were used in 58.7% of patients. Use of and higher doses were strongly associated with HF trial-relevant outcomes. These associations were similar regardless of other risk markers. In HFpEF/HFmrEF trials, requiring loop diuretics as an enrichment factor will reduce the number of eligible patients but increase event rates considerably.