The influence of internally architected voids in the creation of high-strength, low-weight 3D-printed cobalt-chromium prototypes.

Background: The additive manufacturing technology made the topology optimization technique feasible. This technique can indefinitely reduce the weight of the printed items with a promising increase in the mechanical properties of that item. Materials and Methods: In the current experimental study, 50 samples were fabricated for a 3-point bending test. They were divided into (n = 5) as a control Group 1 free of internal geometries, (n = 15) for each of Groups 2-4, and they were subdivided into (n = 5) for each percentage of reduction per volume (10%, 15%, and 20%). Spherical, ovoid, and diamond shapes were each group's fundamental geometries, respectively. Cylindrical tunnels connected the voids in each group. Radiographic images were performed to validate the created geometries, the weight was measured, and flexural strength and modulus of elasticity were calculated. Data were analyzed by one-way ANOVA and Duncan's post hoc tests at P < 0.05. Results: The weight results showed a significant reduction in mass. The flexural strength of Group 2 at a 10% reduction per volume had the highest mean significantly without compromising the elastic modulus. In comparison, the means of group 4 at 20% reduction showed the lowest level of toughness. Conclusion: The weight was reduced according to the reduction percentage. The flexural strength of Group 2 at a 10% reduction showed the highest degree of toughness among all groups. The void shape and density influenced the mechanical properties tested.

The role of internal architecture in producing high-strength 3D printed cobalt-chromium objects.

PURPOSE: The objectives of the current study were to estimate the influence of self-reinforced hollow structures with a graded density on the dimensional accuracy, weight, and mechanical properties of Co-Cr objects printed with the direct metal laser sintering (DMLS) technique. MATERIALS AND METHODS: Sixty-five dog-bone samples were manufactured to evaluate the dimensional accuracy of printing, weight, and tensile properties of DMLS printed Co-Cr. They were divided into Group 1 (control) (n = 5), Group 2, 3, and 4 with incorporated hollow structures based on (spherical, elliptical, and diamond) shapes; they were subdivided into subgroups (n = 5) according to the volumetric reduction (10%, 15%, 20% and 25%). Radiographic imaging and microscopic analysis of the fractographs were conducted to validate the created geometries; the dimensional accuracy, weight, yield tensile strength, and modulus of elasticity were calculated. The data were estimated by one-way ANOVA and Duncan's tests at P < .05. RESULTS: The accuracy test showed an insignificant difference in the x, y, z directions in all printed groups. The weight was significantly reduced proportionally to the reduced volume fraction. The yield strength and elastic modulus of the control group and Group 2 at 10% volume reduction were comparable and significantly higher than the other subgroups. CONCLUSION: The printing accuracy was not affected by the presence or type of the hollow geometry. The weight of Group 2 at 10% reduction was significantly lower than that of the control group. The yield strength and elastic modulus of the Group 2 at a 10% reduction showed means equivalent to the compact objects and were significantly higher than other subgroups.

Diversity trends in traumatic brain injury clinical trials in the United States.

BACKGROUND: This study aims to understand the demographic representation of patients in Traumatic Brain Injury (TBI) clinical trials by evaluating the proportions of patients from various demographic categories amongst completed TBI clinical trials in the United States. METHODS: ClinicalTrials.gov was queried for active TBI clinical trials. One hundred and eight completed trials in the United States were selected based on inclusion criteria, and information regarding intervention, setting, age, sex, race, and ethnicity was extracted. 2002-2006 TBI incidence data was obtained from the CDC. Chi-squared testing was applied to analyze the relationship between distributions of race and sex in the collected clinical trials and the national TBI data, and logistic regression was conducted to identify variables that may predict reporting of race or ethnicity. RESULTS: About 53.7% of selected clinical trials reported racial data and 34.3% reported ethnicity data. Logistic regression identified that clinical trials in defined phases were more likely to report racial data (p = 0.047 [1.015, 9.603]). CONCLUSION: Current TBI trials do not consistently report race or ethnicity data. Future efforts to ensure equitable representation in clinical trials may involve reform of recruitment processes and accountability measures implemented within the grant application process to ensure proper racial and ethnicity data reporting.

Shifts in Reduction Mammaplasty Surgical Volumes With the Emergence of a Global Pandemic.

INTRODUCTION: The onset of the COVID-19 pandemic resulted in significant changes to the surgical caseload for various surgery departments across the United States. As medical institutions prioritized resources for the expected increase in patient volumes due to the SARS-CoV-2 viral infection, surgical departments saw a decrease in nonemergent and elective surgical procedures. Reduction mammoplasties, which are largely covered by insurance, are among the elective procedures that provide significant revenue to the hospital. This expected decline in procedures suggests a potential decline in revenue provided by the plastic surgery department of a hospital. The purpose of this study was to analyze the loss of revenue experienced by a single academic medical institution due to changes in breast reduction mammoplasty volumes during the COVID-19 pandemic. METHODS: Upon institutional review board approval, using the Augusta University Medical Center's Financial Billing Data, 373 patients who underwent bilateral reduction mammoplasty were queried. A time horizon of March 2019 to February 2022 was used to determine the pre- and post-COVID case load and charges that were incurred. Statistical analysis to compare the prior 12 months and after 24 months of COVID was conducted using 2 samples of equal variance t test and F test confirming equal variance. RESULTS: There was a statistically significant increase in the number of reduction mammoplasties performed per month from the year before the onset of COVID-19 (March 2020) to the 2 years after (6.6-11.4 per month, P = 0.0024). There was a statistically significant increase in the per-month charges from the AU Health system for reduction mammoplasties for the same period ($31,780.92-$52,113.34 per month, P = 0.0054). Although there was an increase in per-month revenue from reduction mammoplasties, this increase failed to reach statistical significance ($7,059.95-$10,423.51 per month, P = 0.064). CONCLUSIONS: The plastic surgery department saw a statistically significant increase in reduction mammoplasty cases and subsequent charges in the post-COVID cohort. These findings suggest that the emergence of a nationwide pandemic did not necessarily lead to a decrease in the volume of nonemergent surgical cases despite an expected decrease in caseload due to the need to reallocate hospital resources. On the contrary, there was an increase in caseload suggesting that there may be other factors contributing to patients' pursuance of reduction mammoplasty post-COVID including convenience, resulting from time off due to pandemic, meeting insurance-covered reduction criteria, and projected recovery time.

Salivary gland adenoid cystic carcinoma in the U.S population: Importance of grade, site of metastases, and adjuvant radiation for survival.

BACKGROUND: Adenoid cystic carcinoma (AdCC) is a rare and relatively heterogenous salivary gland malignancy, for which there is debate regarding grading, and clinical prognostic factors, including the role of adjuvant radiotherapy. METHODS: Surveillance, Epidemiology, and End Results (SEER) data were reviewed for AdCC cases from 2000 to 2018. RESULTS: A total of 1978 patients with AdCC were identified. Most patients were between 50 and 59 years of age (21.4 %), female (59.9 %), and Caucasian (76.8 %). Most tumors were localized at presentation (44.3 %), and moderately differentiated (or grade II) (43.7 %). Overall and DSS 5-year survival rates were 70.7 % (95 % CI, 69.9-78.8), and 78.6 % (95 % CI, 77.6-79.6). The best overall 5-year survival rate was observed for those treated with surgery plus radiation, 76.8 % (95 % CI, 75.5-78.1). Multivariate analysis revealed male sex, age > 65 (H.R. 2.659 (95 % CI,2.291-3.098), p < .001), grade III/IV (H.R.5.172 (95 % CI, 3.418-7.824), p < .001), nodal metastasis, distant metastasis (H.R. 2.400 (95 % CI, 2.178-2.645), p < .001), chemotherapy only, and combination therapy as negative prognostic factors, and receiving surgery plus radiation therapy (H.R.0.586 (95 % CI, 0.505-0.679), p < .001) as a positive prognostic factor. When limited just to the lungs, had much better survival than those patients with distant metastases to other sites such as the bones and liver (p < .001). CONCLUSION: This SEER study identifies grade, particularly III and IV, to be the strongest single predictor of worse survival. Patients did best when treated with surgery and postoperative radiotherapy. These results can inform future management of patients with this challenging cancer type.

Who enrolls and why? Examining center-specific underlying patterns behind enrollment: a New York City-based traumatic brain injury model systems study.

BACKGROUND: To elucidate the sociodemographic and study factors involved in enrollment in the Traumatic Brain Injury Model System (TBIMS) database, this study examined the effect of a variety of variables on enrollment at a local TBIMS center. METHODS: A sample of 654 individuals from the local TBIMS center was studied examining enrollment by age, gender, race, ethnicity, homelessness status at date of injury, history of homelessness, health insurance status, presence of social support, primary language, consenting in hospital or after discharge, and the need for an interpreter. Binary logistic regression was conducted to identify variables that predict center-based enrollment into TBIMS. RESULTS: Results demonstrated that older age was associated with decreasing enrollment (OR = 0.99, p = 0.01), needing an interpreter made enrollment less likely (OR = 0.33, p < 0.01), being primarily Spanish speaking predicted enrollment (OR = 3.20, p = 0.02), Hispanic ethnicity predicted enrollment (OR = 7.31, p = 0.03), and approaching individuals in the hospital predicted enrollment (OR = 6.94, p < 0.01). Here, OR denotes the odds ratio estimate from a logistic regression model and P denotes the corresponding p-value. CONCLUSIONS: These results can be useful in driving enrollment strategies at this center for other similar TBI research, and to contribute a representative TBI sample to the national database.

Use of Advanced Diagnostics for Timely Identification of Travel-associated Leptospira santarosai Infection in Four Adolescents Through Plasma Microbial Cell-free DNA Sequencing With the Karius Test.

BACKGROUND: Leptospirosis is an important zoonotic infection worldwide. Diagnosis of leptospirosis is challenging given its nonspecific clinical symptoms that overlap with other acute febrile illnesses and limitations with conventional diagnostic testing. Alternative advanced diagnostics, such as microbial cell-free DNA (mcfDNA), are increasingly being used to aid in the diagnosis of infections and can be applied to pathogens with public health importance such as Leptospira , a nationally notifiable disease. METHODS: The Karius Test uses plasma mcfDNA sequencing to detect and quantify DNA-based pathogens. This test offered through the Karius lab detected 4 cases of Leptospira santarosai during a 5-month period across the United States in 2021 and were clinically reviewed. RESULTS: In our case series, 4 adolescents with recent travel to Central America (Costa Rica, n = 3 and Belize, n = 1) from April to August 2021 were diagnosed with leptospirosis. While a large workup was performed in all cases, mcfDNA testing was the first test to detect L. santarosai as the microbiological diagnosis in all cases. CONCLUSIONS: Results of the Karius Test enabled rapid, noninvasive diagnosis of leptospirosis allowing for targeted therapy. Use of mcfDNA can be utilized for diagnosis of pathogens where conventional testing is challenging or limited. This in turn can enable quick diagnosis for targeted treatment and potentially aid in supporting case definitions of reportable diseases of public health concern.

Serial Quantitation of Plasma Microbial Cell-Free DNA Before and After Diagnosis of Pulmonary Invasive Mold Infections After Hematopoietic Cell Transplant.

BACKGROUND: Plasma microbial cell-free DNA sequencing (mcfDNA-Seq) is a noninvasive test for microbial diagnosis of invasive mold infection (IMI). The utility of mcfDNA-Seq for predicting IMI onset and the clinical implications of mcfDNA concentrations are unknown. METHODS: We retrospectively tested plasma from hematopoietic cell transplant (HCT) recipients with pulmonary IMI and ≥1 mold identified by mcfDNA-Seq in plasma collected within 14 days of clinical diagnosis. Samples collected from up to 4 weeks before and 4 weeks after IMI diagnosis were evaluated using mcfDNA-Seq. RESULTS: Thirty-five HCT recipients with 39 IMIs (16 Aspergillus and 23 non-Aspergillus infections) were included. Pathogenic molds were detected in 38%, 26%, 11%, and 0% of samples collected during the first, second, third, and fourth week before clinical diagnosis, respectively. In non-Aspergillus infections, median mcfDNA concentrations in samples collected within 3 days of clinical diagnosis were higher in infections with versus without extrapulmonary spread (4.3 vs 3.3 log10 molecules per microliter [mpm], P = .02), and all patients (8/8) with mcfDNA concentrations >4.0 log10 mpm died within 42 days after clinical diagnosis. CONCLUSIONS: Plasma mcfDNA-Seq can identify pathogenic molds up to 3 weeks before clinical diagnosis of pulmonary IMI. Plasma mcfDNA concentrations may correlate with extrapulmonary spread and mortality in non-Aspergillus IMI.

Noninvasive diagnosis of secondary infections in COVID-19 by sequencing of plasma microbial cell-free DNA.

Secondary infection (SI) diagnosis in severe COVID-19 remains challenging. We correlated metagenomic sequencing of plasma microbial cell-free DNA (mcfDNA-Seq) with clinical SI assessment, immune response, and outcomes. We classified 42 COVID-19 inpatients as microbiologically confirmed-SI (Micro-SI, n = 8), clinically diagnosed-SI (Clinical-SI, n = 13, i.e., empiric antimicrobials), or no-clinical-suspicion-for-SI (No-Suspected-SI, n = 21). McfDNA-Seq was successful in 73% of samples. McfDNA detection was higher in Micro-SI (94%) compared to Clinical-SI (57%, p = 0.03), and unexpectedly high in No-Suspected-SI (83%), similar to Micro-SI. We detected culture-concordant mcfDNA species in 81% of Micro-SI samples. McfDNA correlated with LRT 16S rRNA bacterial burden (r = 0.74, p = 0.02), and biomarkers (white blood cell count, IL-6, IL-8, SPD, all p < 0.05). McfDNA levels were predictive of worse 90-day survival (hazard ratio 1.30 [1.02-1.64] for each log10 mcfDNA, p = 0.03). High mcfDNA levels in COVID-19 patients without clinical SI suspicion may suggest SI under-diagnosis. McfDNA-Seq offers a non-invasive diagnostic tool for pathogen identification, with prognostic value on clinical outcomes.

Demographics and Clinicopathologic Profile of Pulmonary Sarcomatoid Carcinoma with Survival Analysis and Genomic Landscape.

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small cell lung cancer (NSCLC) with an aggressive clinical nature and poor prognosis. With novel targeted therapeutics being developed, new ways to effectively treat PSC are emerging. In this study, we analyze demographics, tumor characteristics, treatment modalities, and outcomes of PSC and genetic mutations in PSC. Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) database were reviewed to analyze cases of pulmonary sarcomatoid carcinoma from 2000 to 2018. The molecular data with the most common mutations in PSC were extracted from the Catalogue Of Somatic Mutations in Cancer (COSMIC) database. Results: A total of 5259 patients with PSC were identified. Most patients were between 70 and 79 years of age (32.2%), male (59.1%), and Caucasian (83.7%). The male-to-female ratio was 1.45:1. Most tumors were between 1 and 7 cm in size (69.4%) and poorly differentiated (grade III) (72.9%). The overall 5-year survival was 15.6% (95% confidence interval (95% CI) = 14.4-16.9)), and the cause-specific 5-year survival was 19.7% (95% CI = 18.3-21.1). The five-year survival for those treated with each modality were as follows: chemotherapy, 19.9% (95% CI = 17.7-22.2); surgery, 41.7% (95% CI = 38.9-44.6); radiation, 19.1% (95% CI = 15.1-23.5); and multimodality therapy (surgery and chemoradiation), 24.8% (95% CI = 17.6-32.7). On multivariable analysis, age, male gender, distant stage, tumor size, bone metastasis, brain metastasis, and liver metastasis were associated with increased mortality, and chemotherapy and surgery were associated with reduced mortality (p < 0.001). The best survival outcomes were achieved with surgery. The most common mutations identified in COSMIC data were TP53 31%, ARID1A 23%, NF1 17%, SMARCA4 16%, and KMT2D 9%. Conclusions: PSC is a rare and aggressive subtype of NSCLC, usually affecting Caucasian males between 70 and 79. Male gender, older age, and distant spread were associated with poor clinical outcomes. Treatment with surgery was associated with better survival outcomes.

Prophylactic Colchicine After Radiofrequency Ablation of Atrial Fibrillation: The PAPERS Study.

BACKGROUND: Pericarditis is common after radiofrequency ablation for atrial fibrillation (AF). OBJECTIVES: Study investigators hypothesized an empirical post-AF ablation treatment protocol with colchicine may reduce the incidence and severity of pericarditis. PAPERS (Post-Ablation PEricarditis Reduction Study) aimed to quantify the risks and benefits associated with prophylactic use of colchicine to prevent pericarditis following AF ablation. METHODS: PAPERS is a multicenter, prospective, randomized controlled study. Patients were randomized on the day of the procedure to receive no postprocedure prophylaxis (group A; standard of care arm) or colchicine 0.6 mg orally twice daily for 7 days starting immediately post-procedure (group B; study arm). All participants underwent a follow-up survey at 14 days postoperatively. The primary endpoint was the development of clinical pericarditis within 2 weeks following ablation. Secondary outcomes included the incidence of pericarditis by ablation type and medical therapy. RESULTS: Among 139 patients enrolled, 66 were randomized to standard of care (group A), and 73 patients were randomized to the colchicine arm (group B). The primary outcome of clinical pericarditis was reached in 7 of 66 (10.6%) patients in group A and in 7 of 73 (9.6%) patients in group B (P = 0.84). The rate of gastrointestinal discomfort was 10 of 66 (15%) in group A and 34 of 73 (47%) in group B (P < 0.001). There was an increased incidence of pericarditis in patients who underwent cavotricuspid isthmus ablation (17 of 50; 34%) in addition to pulmonary vein isolation (6 of 69; 8.7%; P = 0.001). CONCLUSIONS: Prophylactic colchicine therapy initiated after the ablation procedure in patients with AF did not affect the incidence of post-ablation pericarditis and was associated with an increased incidence of gastrointestinal side effects.

Robust odor identification in novel olfactory environments in mice.

Relevant odors signaling food, mates, or predators can be masked by unpredictable mixtures of less relevant background odors. Here, we developed a mouse behavioral paradigm to test the role played by the novelty of the background odors. During the task, mice identified target odors in previously learned background odors and were challenged by catch trials with novel background odors, a task similar to visual CAPTCHA. Female wild-type (WT) mice could accurately identify known targets in novel background odors. WT mice performance was higher than linear classifiers and the nearest neighbor classifier trained using olfactory bulb glomerular activation patterns. Performance was more consistent with an odor deconvolution method. We also used our task to investigate the performance of female Cntnap2-/- mice, which show some autism-like behaviors. Cntnap2-/- mice had glomerular activation patterns similar to WT mice and matched WT mice target detection for known background odors. However, Cntnap2-/- mice performance fell almost to chance levels in the presence of novel backgrounds. Our findings suggest that mice use a robust algorithm for detecting odors in novel environments and this computation is impaired in Cntnap2-/- mice.

Microbial Cell-Free DNA Identifies the Causative Pathogen in Infective Endocarditis and Remains Detectable Longer Than Conventional Blood Culture in Patients with Prior Antibiotic Therapy.

BACKGROUND: The diagnosis of infective endocarditis (IE) can be difficult, particularly if blood cultures fail to yield a pathogen. This study evaluates the potential utility of microbial cell-free DNA (mcfDNA) as a tool to identify the microbial etiology of IE. METHODS: Blood samples from patients with suspected IE were serially collected. mcfDNA was extracted from plasma and underwent next-generation sequencing. Reads were aligned against a library containing DNA sequences belonging to >1400 different pathogens. mcfDNA from organisms present above a statistical threshold were reported and quantified in molecules per milliliter (MPM). Additional mcfDNA was collected on each subject every 2-3 days for a total of 7 collections or until discharge. RESULTS: Of 30 enrolled patients with suspected IE, 23 had definite IE, 2 had possible IE, and IE was rejected in 5 patients by modified Duke Criteria. Only the 23 patients with definite IE were included for analysis. Both mcfDNA and blood cultures achieved a sensitivity of 87%. The median duration of positivity from antibiotic treatment initiation was estimated to be approximately 38.1 days for mcfDNA versus 3.7 days for blood culture (proportional odds, 2.952; P = .02771), using a semiparametric survival analysis. mcfDNA (log10) levels significantly declined (-0.3 MPM log10 units, 95% credible interval -0.45 to -0.14) after surgical source control was performed (pre- vs postprocedure, posterior probability >0.99). CONCLUSION: mcfDNA accurately identifies the microbial etiology of IE. Sequential mcfDNA levels may ultimately help to individualize therapy by estimating a patient's burden of infection and response to treatment.

Atrial Flutter Masquerading as an ST-segment-elevation Myocardial Infarction in a Patient with Dextrocardia.

Electrocardiogram (ECG) findings suggestive of an ST-segment-elevation myocardial infarction (STEMI) often lead to emergent left heart catheterization. Occasionally, non-coronary conditions mimic ECG findings of STEMI, resulting in an increased risk and expenses from emergent transportation and procedures. In this report, we describe diagnostic and management strategies for a case of 1:1 atrial flutter in a patient with dextrocardia presenting as a STEMI.

Diagnostic utility of early premature ventricular complexes in differentiating atrioventricular reentrant and atrioventricular nodal reentrant tachycardias.

BACKGROUND: His-refractory premature ventricular complexes perturbing a supraventricular tachycardia (SVT) establish the presence of an accessory pathway (AP). Earlier premature ventricular complexes (ErPVCs) may perturb SVTs but are considered nondiagnostic. OBJECTIVE: The purpose of this study was to test the hypothesis that an ErPVC will always show a difference >35 ms in its advancement of the next atrial activation during atrioventricular nodal reentrant tachycardia (AVNRT). During atrioventricular reentrant tachycardia (AVRT), a PVC delivered close to the circuit can result in greater advancement of atrial activation due to retrograde conduction via an AP. Thus, an AP response, defined as ErPVC (H1S2) advancing the subsequent atrial activation (A1-A2) more than this minimum difference (A1A2 ≤ H1S2+35 ms), establishes the presence of an AP. METHODS: Sixty-five consecutive patients with SVT were retrospectively evaluated. ErPVCs were defined when the ventricular pacing stimulus was >35 ms ahead of the His during tachycardia. RESULTS: Among the 65 cases, 43 were AVNRT and 22 AVRT. Fourteen AVRT cases had an AP response with a mean H1S2+35 ms of 336 ± 58 ms and A1A2 of 309 ± 51ms. No AVNRT cases had an AP response. The specificity of an AP response to ErPVC in predicting AVRT was 100%. CONCLUSION: An AP response to PVCs (A1A2 ≤ H1S2+35 ms) is 100% specific for the presence of an AP.

A Rare Etiology for Ascending Paralysis in an Infant.

An 11-month-old male infant with ascending paralysis had an unremarkable initial cerebrospinal fluid (CSF) analysis and imaging. Progressive neurological symptoms resulted in repeated CSF sampling, microscopy, and plasma microbial cell-free DNA next-generation sequencing analysis, that in combination with epidemiology, confirmed the diagnosis.

Persistent 2-for-1 Atrioventricular Node Anterograde Conduction During a Supraventricular Tachycardia.

We present a case of persistent dual AV node conduction during AV node reentry tachycardia as a new clinical manifestation of 2-for-1 AV node conduction. The interpretation of the complex physiology ponders the possibility of an accessory pathway mediated atrioventricular reentry existing with more ventricular than atrial events.

Utility of severity assessment tools in COVID-19 pneumonia: a multicentre observational study.

BACKGROUND: Severity scores in pneumonia and sepsis are being applied to SARS-CoV-2 infection. We aimed to assess whether these severity scores are accurate predictors of early adverse outcomes in COVID-19. METHODS: We conducted a multicentre observational study of hospitalised SARS-CoV-2 infection. We assessed risk scores (CURB65, qSOFA, Lac-CURB65, MuLBSTA and NEWS2) in relation to admission to intensive care or death within 7 days of admission, defined as early severe adverse events (ESAE). The 4C Mortality Score was also assessed in a sub-cohort of patients. FINDINGS: In 2,387 participants, the overall mortality was 18%. In all scores examined, increasing score was associated with increased risk of ESAE. Area under the curve (AUC) to predict ESAE for CURB65, qSOFA, Lac-CURB65, MuLBSTA and NEWS2 were 0.61, 0.62, 0.59, 0.59 and 0.68, respectively. AUC to predict ESAE was 0.60 with ISARIC 4C Mortality Score. CONCLUSION: None of the scores examined accurately predicted ESAE in SARS-CoV-2 infection. Non-validated scores should not be used to inform clinical decision making in COVID-19.

Perspective on the Role of Four Beta-blockers in Heart Failure.

BACKGROUND: The current recommendations of the American College of Cardiology/ American Heart Association and a previous Bayesian analysis clearly show a mortality benefit with the use of ß- blockers in chronic HF, especially for bisoprolol, carvedilol, and sustained-release metoprolol succinate. OBJECTIVE: The main objective was to report the evidence on the use of the afore-mentioned ß-blockers in subjects with heart failure and to characterize the stages of heart failure in response to the four different ß-blockers. Furthermore, it shed light on the patient's satisfaction and improved quality of life using the afore-mentioned ß-blockers in subjects with heart failure. METHODS: The current perspective presented the clinical outcomes, including hospitalization, morbidity, mortality, patient's satisfaction, and quality of life, of four beta (ß)-blockers, namely bisoprolol, carvedilol, metoprolol succinate, and nebivolol in different stages of heart failure. RESULTS: The use of these three agents should be recommended for all stable subjects with current or previous symptoms of heart failure and heart failure with reduced ejection fraction unless there is any contraindication. The fore-mentioned ß-blockers (bisoprolol, carvedilol, and metoprolol succinate) can be initiated early, even in stable and symptom-free (at rest) subjects with heart failure. ß-blockers in heart failure should be commenced at small doses and then titrated upward as tolerated to achieve the desired clinical effects on heart rate and symptom control. CONCLUSION: Cardiologists should weigh the benefit-risk in subjects with heart failure and other coexisting cardiovascular problems such as atrial fibrillation and diabetes.

Microbial Cell-Free DNA Identifies Etiology of Bloodstream Infections, Persists Longer Than Conventional Blood Cultures, and Its Duration of Detection Is Associated With Metastatic Infection in Patients With Staphylococcus aureus and Gram-Negative Bacteremia.

BACKGROUND: Microbial cell-free DNA (mcfDNA) sequencing of plasma can identify the presence of a pathogen in a host. In this study, we evaluated the duration of pathogen detection by mcfDNA sequencing vs conventional blood culture in patients with bacteremia. METHODS: Blood samples from patients with culture-confirmed bloodstream infection were collected within 24 hours of the index positive blood culture and 48 to 72 hours thereafter. mcfDNA was extracted from plasma, and next-generation sequencing was applied. Reads were aligned against a curated pathogen database. Statistical significance was defined with Bonferroni adjustment for multiple comparisons (P < .0033). RESULTS: A total of 175 patients with Staphylococcus aureus bacteremia (n = 66), gram-negative bacteremia (n = 74), or noninfected controls (n = 35) were enrolled. The overall sensitivity of mcfDNA sequencing compared with index blood culture was 89.3% (125 of 140), and the specificity was 74.3%. Among patients with bacteremia, pathogen-specific mcfDNA remained detectable for significantly longer than conventional blood cultures (median 15 days vs 2 days; P < .0001). Each additional day of mcfDNA detection significantly increased the odds of metastatic infection (odds ratio, 2.89; 95% confidence interval, 1.53-5.46; P = .0011). CONCLUSIONS: Pathogen mcfDNA identified the bacterial etiology of bloodstream infection for a significantly longer interval than conventional cultures, and its duration of detection was associated with increased risk for metastatic infection. mcfDNA could play a role in the diagnosis of partially treated endovascular infections.