US Centers Research Articles

Impact of neutrophil-to-lymphocyte ratio on clinical outcomes in patients with or without chronic kidney disease undergoing percutaneous coronary intervention

Abstract Background Neutrophil-to-lymphocyte ratio (NLR) has recently emerged as inexpensive inflammatory biomarker associated with worse cardiovascular outcomes. However, little is known about its role in risk stratification of patients with both chronic kidney disease (CKD) and coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). Purpose We aimed to evaluate the clinical impact of baseline NLR in patients with and without CKD undergoing PCI. Methods We retrospectively evaluated all consecutive patients undergoing PCI between 2012-2022 in a large tertiary US center. We excluded patients without available NLR and those who were deemed to have active hematological or infective diseases, including patients with extremely low or high lymphocyte and neutrophil counts or with hs-CRP above 10 mg/L. Quartiles of NLR were derived in the overall population and patients were stratified according to presence of CKD (eGFR < 60 ml/min). Within each group, we estimated the risk of adverse events using the lowest NLR quartile as reference. The primary endpoint was 12-month incidence of major adverse cardiovascular events (MACE), defined as the composite of all-cause death, myocardial infarction, or stroke. Secondary endpoints included incidence of clinically relevant bleeding and contrast-associated acute kidney injury (CA-AKI), defined as ≥ 0.3 mg/dL or ≥ 50% serum creatinine increase from baseline. Results A total of 7,287 patients were included in the analysis; of these 2,008 (27.6%) had CKD and 5,279 (72.4%) did not. CKD patients (mean eGFR 40.8±16.1 ml/min) were older, had more comorbidities, and presented with higher hs-CRP levels and a greater estimated risk of CA-AKI. Overall, patients with elevated NLR had more severe CAD and underwent more complex PCI. In CKD patients, incidence of adverse events increased stepwise and those in the 4th NLR quartile had the highest adjusted risks of MACE (HRadj 1.86, 95% CI 1.12-3.08; P=0.012), all cause death (HRadj 2.44, 95% CI 1.18-5.05; P=0.003) and bleeding (HRadj 1.74, 95% CI 1.07-2.84; P=0.002) at 1 year, as compared to those in the lowest quartile (Table 1). In patients without CKD, MACE and all-cause death incidences were numerically higher in the 4th quartile but risk estimates were no longer statistically significant after adjustment. The overall incidence of CA-AKI was much greater in the CKD group. When compared to the lowest quartile, patients in the 4th NLR quartile showed a trend for higher risk of CA-AKI in CKD group, while they had a significant increased risk in non-CKD group (Figure 1). Conclusions Elevated NLR is strongly associated with higher risk of MACE and all-cause mortality in CKD patients. Conversely, the risk of bleeding and CA-AKI is increased with elevated NLR in both CKD and non-CKD patients. Thus, NLR may further inform risk stratification of CKD patients undergoing PCI.

Increased adoption of IL-1 pathway inhibition and the steroid-sparing paradigm shift: temporal trends in recurrent pericarditis treatment from the RESONANCE patient registry

Abstract Background Recurrent pericarditis (RP) is a chronic autoinflammatory disease mediated by IL-1 that requires long-term treatment. While the 2015 European Society of Cardiology Guidelines position IL-1 pathway inhibition only after corticosteroids, complications associated with long-term steroid use underscore the importance of steroid-sparing strategies. Rilonacept, an IL-1α and IL-1β cytokine trap, is the only FDA-approved treatment for RP (available since April 2021). RESONANCE, an ongoing 5-year non-interventional US registry of patients (pts) with RP, has collected real-world data from pts cared for by cardiologists with a focus on pericardial disease, with a goal of informing contemporary RP clinical management. Purpose Analysis of temporal trends in RP management from RESONANCE. Methods From a database cut-off (DCO) on 21 December 2023, patient demographics and disease characteristics are reported for 242 active RP pts (excluding RHAPSODY prior participants) at 20 US sites (median [Q1:Q3] 2.1 [1.5:2.6] years and 556 patient-years [PY] of observation). Complete medication class use data were available for 239 pts (total 546 PY). Proportional medication class use prior to initiating rilonacept was analyzed annually across the observation period. Results Mean (standard deviation) age at DCO was 50.2 (16.6) years; 58.1% were female. Median [Q1:Q3] disease duration at DCO from index pericarditis episode was 3.1 [2.2:5] years. Median [Q1:Q3] number of prior recurrences at enrollment was 3 [2:5]. Prior to rilonacept availability, NSAIDs/Colchicine/Aspirin represented the highest proportion of treatment (73% of PY); steroid use was 9% of PY, IL-1 pathway inhibition (anakinra) was 13% of PY, and conventional synthetic disease modifying antirheumatic drugs (csDMARDs) were 0.46% PY (no RP-specific treatment was 5% of PY) (Fig 1). In the years since rilonacept availability, proportional IL-1 pathway inhibition use has increased, from 13% of PY in 2020-21 to 26% of PY in 2023, driven by an increase in rilonacept use (6%, 13%, 16% of PY in 2021, 2022, and 2023, respectively). Over that same period, proportional NSAIDs/Colchicine/Aspirin use (57%-63% of PY) has been consistently 6-times more than proportional steroid use (10%-11% of PY). Among pts who initiated rilonacept (n=81), similar proportions transitioned from NSAIDs/Colchicine/Aspirin as from corticosteroids (Fig 2), a robust trend observed each year. Of those pts transitioning from corticosteroids, 1/3 had used corticosteroids for <30 days and 1/3 for >6 months. Conclusions Real-world data from the RESONANCE registry reveal a temporal shift in RP management in US centers with RP-focused cardiologists, with increased proportional IL-1 pathway inhibition use since rilonacept availability in 2021. Advancing beyond 2015 guideline recommendations, IL-1 pathway inhibition is often being used as steroid-sparing treatment, i.e., after colchicine instead of chronic corticosteroids.

Symptoms and ASCVD score fail to identify majority of the patients at risk of first myocardial infarction

Abstract Background Cardiovascular disease screening has long relied on the presence of symptoms like chest pain or on the Atherosclerotic Cardiovascular Disease (ASCVD) risk score, which is typically initiated at age 40. However, current research suggests that the ASCVD risk score may not incorporate a comprehensive range of factors and should be started earlier. Furthermore, the absence of symptoms such as angina in some patients prior to acute coronary syndrome (ACS) casts doubt on the reliability of symptom-based screening methods. Purpose This study aimed to evaluate the effectiveness of the ASCVD risk score and chest pain as predictors for ACS. Methods We retrospectively analyzed the data of all patients of 65 or younger who presented with their first ACS event in a single US center from January 2020 to January 2024. We collected the demographic and clinical data, including age, sex, lipid panel, blood pressure, medical history, onset of symptoms, and calculated their individual ASCVD risk score. We explored whether these patients, if assessed one week before their ACS event, would have been identified as at risk and thus prescribed lipid lowering or recommended for further diagnostic tests. Results Among 166 patients presenting with ACS, 64 (39%) were considered low risk with an ASCVD risk score of <5 or too low to calculate. 20 (12%) patients were assessed as borderline risk with an estimated risk score of 5-7.5%. In the intermediate risk category, 20 patients (12%) had a score of 7.5% -10% and 42 patients (25%) were estimated to have a score of >10 to <20%. 14 patients (8%) fell in the high-risk category, and lastly 6 patients had an LDL that was above 190 mg/dl. Regarding symptoms of chest pain or shortness of breath, 14 patients (8%) did not experience any symptoms prior to their presentation, 98 (59%) patients experienced their first episode of symptoms within 48 hours, 19 patients (11%) within 2 days to a week, 10 patients (6%) had CP leading up to their event from a week to a month, 6 patients (4%) in the range of a month to 3 months and 19 patients (11%) had symptoms longer than 3 months prior to their presentation. To summarize if there were seen 1 week prior to their first ACS events, 51% of them were not recommended for statin therapy based on their ASCVD risk score and 67% of patients either had no chest pain until the event or chest pain within 48hrs of onset of their ACS and consequently would not have been routinely screened for coronary artery disease (CAD) by any anatomical or functional methods. Conclusion(s) ASCVD risk score and symptoms fail to identify majority of patient below 65 years of age with their first MI. Given high prevalence of CAD and associated mortality, improved screening tools, in addition to symptomatology or risk scores, would be more effective in identifying individuals at risk.

Initial Safety of Total Talus Replacement Used to Treat Talar Avascular Necrosis.

Total talus replacement (TTR) implants are designed to replace the diseased talar anatomy, reduce pain, maintain ankle range of motion, and restore ankle function after conservative treatments have failed. Currently TTR implants are produced by 3D printing a patient-specific implant designed from the patient's preoperative anatomy. TTR surgery using patient-specific implants is a relatively new technique that remains understudied in the literature. Therefore, the purpose of this investigation was to determine the early safety and potential benefit of the TTR implant in patients with talar avascular necrosis. This retrospective, multicenter, cohort study evaluates the safety and potential benefits of TTR using 3D-printed patient-specific implants across 4 US centers. The primary outcome was the occurrence of early adverse events after TTR surgery. Secondary outcomes including, pain, and physical function were assessed using the pain visual analog scale (VAS), and Patient-Reported Outcomes Measurement Information System (PROMIS) physical function (PF), respectively. The study team analyzed 15 patients with more than 1 year of follow-up. The mean duration of follow-up was 25.9 months (range: 18.3-41 months). Although 33.3% (5 of 15) of patients experienced adverse events, primarily occurring within the initial 6 months postoperatively, 93% (14 of 15) of patients reported implant survivorship. Of the 5 cases (33.3%) resulting in an adverse event, 3 (60.0%) were determined to be unrelated to the subject device, 2 (40.0%) were determined to be possibly procedure-related, and none (0%) were determined to be device-related. Although further studies are needed to compare TTR with the standard of care, the results of this study demonstrate the relative early safety of TTR surgery using a 3D-printed implant for the treatment of challenging talar pathologies. A larger and longer clinical study is required to see if the efficacy of this approach will be statistically and clinically meaningful.

Characteristics, clinical care, and outcomes of sepsis among patients boarding in the emergency department.

Patients who first meet clinical criteria for sepsis while boarding in the emergency department (ED) may not receive optimal sepsis care. Assess the association between ED boarding status and sepsis quality of care and outcomes. We conducted a retrospective cohort study of adult patients admitted to a large academic hospital from July 2021 to October 2023 who had clinical features consistent with sepsis present while physically in the ED. We compared outcomes for patients who experienced time zero (T-0; the time clinical features of sepsis were first present) while boarding in the ED (physically in the ED but admitted to a different service) to those experiencing T-0 while still under the care of the ED provider team. We used logistic regression to estimate the association between ED boarding status at T-0 and compliance with the US Centers for Medicare & Medicaid Services (CMS) Severe Sepsis and Septic Shock: Management Bundle (SEP-1) core measure, individual bundle element compliance, and hospital mortality adjusting for prespecified covariates. In a subgroup analysis among patients who had not already received antibiotics before T-0, we conducted a Cox proportional hazards model to estimate the association between boarding status on time-to-antibiotics. Among 4795 patients meeting a clinical definition of sepsis in the ED, 422 (8.8%) experienced T-0 as ED boarders. These patients were similar in age, sex, and comorbidities compared with patients experiencing T-0 while still under ED care. Fewer patients with T-0 as an ED boarder received SEP-1 compliant care (25% vs. 38%, p < .001), including a lower proportion of fluid resuscitation (15% vs. 26%, p = .004) and lactate assessment (62% vs. 94%, p < .001). Overall, more patients in the ED boarder group received antibiotics within 3 hours, but one-third of patients had already received antibiotics prior to T-0. Among patients who had not already received antibiotics prior to T-0, experiencing T-0 as an ED boarder was associated with a decreased likelihood of receiving antibiotics (hazard ratio [HR]: 0.67 [95% confidence interval [CI], 0.54-0.84]) and longer time to antibiotics from T-0 (142 min vs. 100 min, p = .007). Sepsis patients experiencing T-0 as a boarder in the ED have a lower likelihood of receiving SEP-1 compliant care compared to patients who experience T-0 while still under ED care.

Infodemics and Vaccine Confidence: Protocol for Social Listening and Insight Generation to Inform Action.

In the fall of 2020, the COVID-19 infodemic began to affect public confidence in and demand for COVID-19 vaccines in the United States. While polls indicated what consumers felt regarding COVID-19 vaccines, they did not provide an understanding of why they felt that way or the social and informational influences that factored into vaccine confidence and uptake. It was essential for us to better understand how information ecosystems were affecting the confidence in and demand for COVID-19 vaccines in the United States. The US Centers for Disease Control and Prevention (CDC) established an Insights Unit within the COVID-19 Response's Vaccine Task Force in January 2021 to assist the agency in acting more swiftly to address the questions, concerns, perceptions, and misinformation that appeared to be affecting uptake of COVID-19 vaccines. We established a novel methodology to rapidly detect and report on trends in vaccine confidence and demand to guide communication efforts and improve programmatic quality in near real time. We identified and assessed data sources for inclusion through an informal landscape analysis using a snowball method. Selected data sources provided an expansive look at the information ecosystem of the United States regarding COVID-19 vaccines. The CDC's Vaccinate with Confidence framework and the World Health Organization's behavioral and social drivers for vaccine decision-making framework were selected as guiding principles for interpreting generated insights and their impact. We used qualitative thematic analysis methods and a consensus-building approach to identify prevailing and emerging themes, assess their potential threat to vaccine confidence, and propose actions to increase confidence and demand. As of August 2022, we have produced and distributed 34 reports to >950 recipients within the CDC and externally. State and local health departments, nonprofit organizations, professional associations, and congressional committees have referenced and used the reports for learning about COVID-19 vaccine confidence and demand, developing communication strategies, and demonstrating how the CDC monitored and responded to misinformation. A survey of the reports' end users found that nearly 75% (40/53) of respondents found them "very" or "extremely" relevant and 52% (32/61) used the reports to inform communication strategies. In addition, our methodology underwent continuous process improvement to increase the rigor of the research process, the validity of the findings, and the usability of the reports. This methodology can serve as a diagnostic technique for rapidly identifying opportunities for public health interventions and prevention. As the methodology itself is adaptable, it could be leveraged and scaled for use in a variety of public health settings. Furthermore, it could be considered beyond acute public health crises to support adherence to guidance and recommendations and could be considered within routine monitoring and surveillance systems.

Pregnancy-Related Mortality Disparities During the COVID-19 Pandemic.

Objectives. To compare pregnancy-related mortality ratios (PRMRs) associated with COVID-19 by race/ethnicity, by region of residence, and in states with and without Medicaid expansion. Methods. We used 2020-2021 data from the US Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research in our analysis. We stratified PRMRs by race/ethnicity, census regions, and Medicaid expansion and nonexpansion states. Results. The 2020-2021 PRMR was 40.3 per 100 000 live births. American Indian/ Alaska Native pregnant people had the greatest PRMR, followed by non-Hispanic Blacks and non-Hispanic Native Hawaiians/other Pacific Islanders. PRMRs associated with COVID-19 in the southern region were at least 2 times higher than in other regions and were highest for all pregnant people in the various racial/ethnic groups. PRMRs associated with COVID-19 were lower in Medicaid expansion states than in nonexpansion states. Conclusions. The US COVID-19 epidemic exacerbated racial and ethnic disparities in pregnancy-related mortality. Public Health Implications. The alarming increase in disparities among racial and ethnic pregnant people during the COVID-19 pandemic underscores the need to address social determinants of health at the structural level. (Am J Public Health. Published online ahead of print October 24, 2024:e1-e8. https://doi.org/10.2105/AJPH.2024.307814).

Risk Stratification for Chronic Kidney Disease After Liver Transplant for Metabolic Dysfunction-associated Steatohepatitis (MASH) Cirrhosis: Results From the NailMASH Consortium.

Chronic kidney disease (CKD) is a well-recognized complication in patients undergoing liver transplantation (LT), particularly those with metabolic dysfunction-associated steatohepatitis (MASH), a leading cause of cirrhosis in the modern era. This study sought to refine risk stratification for CKD events post-LT in cirrhosis patients with MASH by leveraging baseline renal function at transplant. A total of 717 MASH cirrhosis patients who had LT (1997-2017) at 7 US centers (NailMASH Consortium) were analyzed. Patients were categorized by estimated glomerular filtration rate (eGFR) at transplant: low (LGFR, eGFR ≤30 mL/min/1.73 m²), medium (MGFR, eGFR >30-≤60 mL/min/1.73 m²), and high (HGFR, eGFR >60 mL/min/1.73 m²). Time-related eGFR intercepts, slopes, and assessments of advanced-stage CKD (aCKD) events, defined as 2 eGFR levels <30 mL/min/1.73 m² separated by ≥90 d, were examined. Post-LT, LGFR group showed increased eGFR, whereas the HGFR group experienced a decline. The 3-mo mark was identified as a "reset point," signifying a new reference level, beyond which a different rate of decline was observed. After 3 mo, mean eGFRs of the LGFR group approached MGFRs, whereas the mean eGFR of the HGFR group continued to decrease but remained higher than other groups during a 60-mo follow-up. LGFR patients had significantly higher aCKD probability than MGFR and HGFR groups. Subanalysis at 3 mo post-LT revealed more aCKD events in the LGFR group compared with MGFR and HGFR groups (P < 0.0001). The study underscores renal impact of LT in MASH cirrhosis, indicating unique eGFR trajectories post-LT tied to baseline eGFR, with a reset point at 3 mo. Monitoring post-LT renal function, especially in those at aCKD risk, is crucial. Renal-sparing immunosuppression may help, regardless of baseline eGFR. Further studies are needed for interventions addressing renal dysfunction of patients with MASH post-LT.

Secular Trends in Physical Growth Among Peruvian Children and Adolescents Living at High Altitudes.

We aim (1) to examine secular trends in height, weight, and waist circumference (WC) among Peruvian children and adolescents living in the city of Junín and (2) to compare their growth status with the World Health Organization (WHO) and US Centers for Disease Control and Prevention (CDC) reference data. The sample included 2874 Peruvians (n = 1681 in the 2009 cohort and n = 1193 in the 2019 cohort) aged 6-16 years from the district of Junín (4107 m of altitude). Height, weight, and WC were measured using standardized protocols. Within each sex, a two-way between-subjects analysis of variance-age, and cohort as main factors and age-by-cohort as the interaction-was used to test for differences in height, weight, and WC. STATA 17 software was used in all statistical analyses. Height revealed a positive secular trend among girls, aged 6-11 years, and among boys up to 14 years of age. Similar positive secular trends in weight and WC were found across all age groups in both boys and girls. Compared to North American peers, children in the 2009 cohort were shorter, lighter, and had a smaller WC. For weight and WC, the 2019 cohort overlapped the 50th percentile across all age groups (except for 16-year-old girls). Both boys' and girls' height, weight, and WC showed positive secular trends between 2009 and 2019, with statistically significant differences varying across age groups. Peruvian youth of both sexes were shorter and lighter than their North American peers.

Outcomes After Brexucabtagene Autoleucel Administered as a Standard Therapy for Adults With Relapsed/Refractory B-Cell ALL.

On the basis of the results of the ZUMA-3 trial, brexucabtagene autoleucel (brexu-cel), a CD19-directed chimeric antigen receptor T-cell therapy, gained US Food and Drug Administration approval in October 2021 for adults with relapsed/refractory (R/R) B-cell ALL (B-ALL). We report outcomes of patients treated with brexu-cel as a standard therapy. We developed a collaboration across 31 US centers to study adults with B-ALL who received brexu-cel outside the context of a clinical trial. Data were collected retrospectively from October 2021 to October 2023. Toxicities were graded per American Society for Transplantation and Cellular Therapy guidelines for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). At the time of data lock, 204 patients had undergone apheresis and 189 were infused. Median follow-up time was 11.4 months. Forty-two percent of patients received brexu-cel in morphologic remission and would have been ineligible for participation in ZUMA-3. After brexu-cel, 151 achieved complete remission (CR), of which 79% were measurable residual disease (MRD) negative remissions. Median progression-free survival (PFS) was 9.5 months and median overall survival was not reached. Grade 3-4 CRS or ICANS occurred in 11% and 31%, respectively. In multivariable analysis, patients receiving consolidative hematopoietic cell transplantation (HCT; hazard ratio, 0.34 [95% CI, 0.14 to 0.85]) after brexu-cel had superior PFS compared with those who did not receive any consolidation or maintenance therapy. Similar to ZUMA-3, high rates of MRD-negative CR were observed after brexu-cel treatment for R/R B-ALL. The use of HCT as consolidation after brexu-cel resulted in improved PFS.

Multicenter Analysis of Valganciclovir Prophylaxis in Pediatric Solid Organ Transplant Recipients

Abstract Background Valganciclovir (VGCV) prophylaxis against cytomegalovirus (CMV) infection and disease has provided an important advance in the management of pediatric solid organ transplantation (SOT) recipients over the past two decades. However, there remain significant questions regarding its relative safety and efficacy, optimal dosing strategies, and toxicities including neutropenia and lymphopenia. We performed a multi-center retrospective study of children post SOT who were to receive at least 3 months of valganciclovir. The primary outcomes were CMV DNAemia while receiving prophylaxis (breakthrough) and post-prophylaxis CMV DNAemia within the first year. Methods The study population included patients ≤ 20 years of age at the time of their first transplant between January 2016 and December 2019 from 8 US centers in PIDTRAN Network. Data for each patient was extracted from the electronic medical record and entered into a REDcap database hosted by St. Jude Children’s Research Hospital. Variables analyzed included demographics, donor/recipient CMV serostatus, immunosuppression, trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis use, rejection, other viral or bacterial infections and one-year survival. Statistics were performed using STATA software for univariate and multivariate models; p-value&amp;lt; 0.05 was considered statistically significant. Results 749 pediatric SOT patients were enrolled over the 3-year study period. Breakthrough DNAemia occurred in 85 (11.4%) patients and post-prophylaxis CMV DNAemia was documented in an additional 46 (6.9%) patients. CMV disease occurred in only 30 patients (4%). In univariate analysis, there were no differences in age, sex, race/ethnicity, or immunosuppression comparing those who experienced breakthrough or post-prophylaxis CMV DNAemia compared to those without CMV DNAemia, but there were differences based on transplanted organ (p&amp;lt; 0.001, liver and lung &amp;gt; heart &amp;gt; kidney) and CMV risk status (high and intermediate) (p&amp;lt;0.001). Neutropenia (p&amp;lt;0.001) and lymphopenia (p=0.003) as well as VGCV discontinuation or dose reduction for perceived toxicity (p&amp;lt;0.001) were associated with breakthrough CMV infection. Bacteremia (p=0.001), EBV viremia (p=0.02), and adenovirus viremia (p=0.002) were also documented more in those with breakthrough compared to those who never had CMV DNAemia. In an adjusted Cox regression hazard model using all significant univariate variables, transplanted organ, CMV risk status, toxicity related VGCV modification (p=0.005), and bacteremia (p=0.01) were independently associated with breakthrough CMV infection. Breakthrough CMV was also associated with rejection (p=0.01) in a separate logistic multivariable model. Both liver (p&amp;lt;0.001) and heart transplant (p&amp;lt;0.001) patients had a greater risk of rejection over the first year of transplantation, but only liver transplant patients had a greater risk of rejection with breakthrough CMV infection (p=0.004). Post prophylaxis CMV DNAemia was associated with mortality at 1 year in the univariate analysis in the full cohort (p=0.001). Conclusion Rates of CMV disease when using valganciclovir prophylaxis were low in this large, multicenter cohort of pediatric SOT recipients. However, breakthrough CMV infection continues to be a problem in intermediate- and high-risk CMV patients and is associated with significant morbidity and rejection, particularly in the liver transplant population. Alternative approaches to prevent breakthrough and post-prophylaxis CMV and with a better safety profile should be studied in pediatric SOT patients.

Chronic total occlusion percutaneous coronary intervention of anomalous coronary arteries: insights from the PROGRESS CTO registry.

There is limited information about the frequency and outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) in anomalous coronary arteries (ACA). We examined the clinical and angiographic characteristics and procedural outcomes of CTO PCI in ACA among 14,173 patients who underwent 14,470 CTO PCIs at 46 US and non-US centers between 2012 and 2023. Of 14,470 CTO PCIs, 36 (0.24%) were CTO PCIs in an ACA. ACA patients had similar baseline characteristics as those without an ACA. The type of ACA in which the CTO lesion was found were as follows: anomalous origin of the right coronary artery (ARCA) (17, 48.5%), anomalous origin of left circumflex coronary artery (9, 25.7%), left anterior descending artery and left circumflex artery with separate origins (4, 11.4%), anomalous origin of the left anterior descending artery (2, 5.7%), dual left anterior descending artery (2, 5.7%) and woven coronary artery 1 (2.8%). The Japan CTO score was similar between both groups (2.17 ± 1.32 vs 2.38 ± 1.26, p = 0.30). The target CTO in ACA patients was more likely to have moderate/severe tortuosity (44% vs 28%, p = 0.035), required more often use of retrograde approach (27% vs 12%, p = 0.028), and was associated with longer procedure (142.5 min vs 112.00 min [74.0, 164.0], p = 0.028) and fluoroscopy (56 min [40, 79 ml] vs 42 min [25, 67], p = 0.014) time and higher contrast volume (260 ml [190, 450] vs 200 ml [150, 300], p = 0.004) but had similar procedural (91.4% vs 85.6%, p = 0.46) and technical (91.4% vs 87.0%, p = 0.59) success. No major adverse cardiac events (MACE) were seen in ACA patients (0% [0] vs 1.9% [281] in non-ACA patients, p = 1.00). Two coronary perforations were reported in ACA CTO PCI (p = 0.7 vs. non-ACA CTO PCI). CTO PCI of ACA comprise 0.24% of all CTO PCIs performed in the PROGRESS CTO registry and was associated with higher procedural complexity but similar technical and procedural success rates and similar MACE compared with non-ACA CTO PCI.

Use Patterns, Technical Challenges and Patient Selection Associated With Single Use Duodenoscopes & Duodenoscopes With Single Use Endcaps In The United States & Canada

Background & AimsThe extent of adoption, patient selection and use patterns of single use duodenoscopes and duodenoscopes with single use endcaps have not yet been characterized, nor have large scale assessments of endoscopist-reported function and challenges. MethodsAn anonymous 6-minute electronic survey assessing use and experience with single use duodensocopes and duodenoscopes with novel design features was distributed to US and Canadian endoscopy centers and responses were analyzed using descriptive statistics. ResultsThe survey was notable for a 70.2% response rate, with representation from academic (68.9%), community (18%) and veterans affairs (8.2%) centers. Most institutions use standard reprocessable duodenoscopes and duodenoscopes with single use endcaps (34.4%), or a mix of standard reprocessable duodenoscopes, duodenoscopes with single use endcaps and single use duodenoscopes (29.5%). No center used only single use duodenoscopes (0%). 10.3% planned to transition to the duodenoscope with a single use endcap, 10.3% to a mix of single use duodenoscopes and duodenoscopes with single use endcap, and 1.7% to single use duodenoscopes alone. Challenges were reported with each type of novel duodenoscope and selection patterns for use were characterized. ConclusionsThis first-of-its-kind large scale survey of use patterns and functionality of newly introduced duodenoscopes is notable for fairly widespread use of the duodenoscopes with single use endcaps and more limited use of the single use duodenoscope. Both novel duodenoscope designs are associated with mechanical limitations that respondents indicate represent challenges to successful completion of ERCPs.

Effects of doxycycline post-exposure prophylaxis for prevention of sexually transmitted infections on gonorrhoea prevalence and antimicrobial resistance among men who have sex with men in the USA: a modelling study

Doxycycline post-exposure prophylaxis (PEP) has been shown to be efficacious for the prevention of bacterial sexually transmitted infections, but resistance implications for Neisseria gonorrhoeae remain unknown. We aimed to use a mathematical model to investigate the anticipated impact of doxycycline PEP on the burden of gonorrhoea and antimicrobial resistance dynamics in men who have sex with men (MSM) in the USA. Using a deterministic compartmental model, characterising gonorrhoea transmission in a US MSM population comprising three sexual activity groups defined by annual partner turnover rates, we introduced doxycycline PEP at various uptake levels (10-90%) among those with high sexual activity. Infections were stratified by symptom status and resistance profile (ie, susceptible, ceftriaxone-resistant, tetracycline-resistant, or dual-resistant), with ceftriaxone the treatment for active infection. As resistance to tetracycline, not doxycycline, is monitored and reported nationally, we used this as a proxy for doxycycline PEP resistance. We compared the 20-year prevalence, incidence rates, and cumulative incidence of gonococcal infection, resistance dynamics (time to 5% prevalence of ceftriaxone resistance, 5% prevalence of dual resistance, and 84% prevalence of tetracycline resistance), and antibiotic consumption with baseline (ie, no doxycycline PEP). Uptake of doxycycline PEP resulted in substantial reductions in the prevalence and incidence of gonorrhoea, but accelerated the spread of tetracycline resistance. The maximum reduction in prevalence over 20years compared with no uptake ranged from 40·3% (IQR 15·3-83·4) with 10% doxycycline PEP uptake to 77·4% (68·4-84·9) with 90%uptake. Similarly, the maximum reduction in the incidence rate ranged from 38·6% (14·1-83·6) with 10% uptake to 77·6% (68·1-84·7) with 90% uptake. Cumulative gonococcal infections were reduced by a median of 14·5% (IQR8·4-21·6) with 10% uptake and up to 46·2% (26·5-59·9) with 90% uptake after 5years, and by 6·5% (3·4-13·0) with 10% uptake and 8·7% (4·3-36·2) with 90% uptake by 20years. In almost all scenarios explored, doxycycline PEP lost clinical effectiveness (defined as 84% prevalence of tetracycline resistance) within the 20-year period, but itslifespan ranged from a median of 12·1years (IQR 9·9-15·7) with 10% uptake to 1·6years (1·3-1·9) with 90%uptake. Doxycycline PEP implementation had minimal impact on extending the clinical lifespan of ceftriaxone monotherapy (5·0years [IQR 4·0-6·2]), with the median time to 5% prevalence of resistance ranging from 4·8years (3·9-6·0) for 90% uptake to 5·0years (4·1-6·2) for 10% uptake. Similarly, the median time to 5%prevalence of dual resistance to ceftriaxone and tetracycline ranged from 4·8years (3·9-6·0) for 90% uptake to 5·8years (4·8-7·4) for 10% uptake. Median decrease in ceftriaxone consumption for high doxycycline PEP uptake levels compared with baseline ranged from 41·7% (27·0-54·3) for 50% uptake to 50·2% (29·3-62·7) for 90% uptake at 5years, but dropped to 11·8% (6·9-32·0) for 50% uptake and 12·1% (7·0-41·6) for 90% uptake after 20years. Notwithstanding the clear benefits of doxycycline PEP for other sexually transmitted infections, for Ngonorrhoeae, model findings suggest that doxycycline PEP is an effective but impermanent solution for reducing infection burden, given eventual selection for resistant strains. This finding presents a challenge for policy makers considering strategies for doxycycline PEP implementation and oversight: the need to balance the clear, short-term clinical benefits with the risk of harm via antimicrobial resistance. US Centers for Disease Control and Prevention, National Institute of Allergy and Infectious Diseases.

Effectiveness and Safety of Cefiderocol in Clinical Practice for Treatment of Patients with Gram-Negative Bacterial Infections: US Interim Results of the PROVE Study.

The international PROVE retrospective chart-review study aims to assess the real-world effectiveness and safety of cefiderocol for treatment of patients with carbapenem-resistant Gram-negative infections. US centers selected hospitalized patients receiving their first cefiderocol treatment for ≥72hours for a Gram-negative bacterial infection (November 2020-March 2023). Patient demographics, clinical characteristics, hospitalization, course of infection, antibiotic use, clinical cure (excluding patients with a relapse/reinfection), clinical response at the end of treatment, microbiology, in-hospital all-cause mortality (IH-ACM) at Day 30, and safety were analyzed using descriptive statistics. This interim analysis included 244 patients. The most frequent infection sites were respiratory tract (55.7%), skin and skin structure (16.8%), and blood (9.8%). The median duration of cefiderocol use was 12 days (interquartile range 8-18.5). Clinical cure was reported for 64.8% (158/244) of patients, clinical response for 74.2% (181/244), and 9.4% (23/244) had relapse/reinfection; 30-day IH-ACM was 18.4% (45/244). Of 82 patients with monomicrobial Pseudomonas aeruginosa infections, 64.6% (n = 53) and 74.4% (n = 61) had clinical cure and clinical response, respectively, and 30-day IH-ACM was 25.6%. Among 43 patients with monomicrobial Acinetobacter baumannii infections, 60.5% (n = 26) and 74.4% (n = 32) had clinical cure and clinical response, respectively, and 30-day IH-ACM was 18.6%. Five patients experienced six adverse drug reactions (one serious event: interstitial nephritis/acute kidney injury), and cefiderocol was discontinued in two cases. Cefiderocol had similar clinical cure and response rates to previous retrospective studies and lower mortality. Cefiderocol was well tolerated in real-world settings in critically ill US patients with problematic Gram-negative pathogens.

Weight loss and health status 10 years after laparoscopic adjustable gastric band insertion in adolescents: a follow-up report from Teen-LABS

BackgroundMetabolic and bariatric surgery is a safe and effective treatment strategy for severe childhood obesity, affecting 10% of US adolescents. ObjectivesThis prospective observational study addresses knowledge gaps related to changes in weight, cardiometabolic risk, and weight-related quality of life (WRQOL) in adolescents 10 years after laparoscopic adjustable gastric band (LAGB) insertion. SettingFive Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) US centers. MethodsAnthropometric, micronutrient, cardiometabolic risk, and WRQOL data were collected on 274 adolescents undergoing metabolic and bariatric surgery, of which 14 participants underwent LAGB insertion (2008–2011). Descriptive analyses compared outcomes from baseline to 10 years. ResultsParticipants were mostly female (86%), White (71%), with a median age of 18.5 years and preoperative median BMI of 49. Baseline prevalence of type 2 diabetes, hypertension, and dyslipidemia were 1 of 14 (7%), 8 of 14 (57%), and 8 of 13 (62%), respectively, versus 10-year prevalence of 1 of 8 (13%), 4 of 10 (40%), and 3 of 9 (33%), respectively. Two participants underwent LAGB removal (years 2 and 3), whereas two converted from LAGB to Roux-en-Y gastric bypass (years 2 and 6). Following initial BMI reduction (−10%) at year 1, 10-year median BMI in the LAGB retention group was 51, representing a 9.2% increase versus baseline. Micronutrient abnormalities and WRQOL remained similar between baseline and 10 years. One participant (1 of 14) withdrew from the study at year 7. ConclusionsLong-term follow-up of this cohort reveals that LAGB had minimal impact on BMI, cardiometabolic risk factors, and WRQOL among adolescents. These results confirm the limited efficacy of LAGB in the pediatric population.

Genomic cluster formation among invasive group A streptococcal infections in the USA: a whole-genome sequencing and population-based surveillance study

Clusters of invasive group Astreptococcal (iGAS) infection, linked to genomically closely related group Astreptococcal (GAS) isolates (referred to as genomic clusters), pose public health threats, and are increasingly identified through whole-genome sequencing (WGS) analysis. In this study, we aimed to assess the risk of genomic cluster formation among iGAS cases not already part of existing genomic clusters. In this WGS and population-based surveillance study, we analysed iGAS case isolates from the Active Bacterial Core surveillance (ABCs), which is part of the US Centers for Disease Control and Prevention's Emerging Infections Program, in ten US states from Jan 1, 2015, to Dec 31, 2019. We included all residents in ABCs sites with iGAS infections meeting the case definition and excluded non-conforming GAS infections and cases with whole-genome assemblies of the isolate containing fewer than 1·5million total bases or more than 150contigs. For iGAS cases we collected basic demographics, underlying conditions, and risk factors for infection from medical records, and for isolates we included emm types, antimicrobial resistance, and presence of virulence-related genes. Two iGAS cases were defined as genomically clustered if their isolates differed by three or less single-nucleotide variants. An iGAS case not clustered with any previous cases at the time of detection, with a minimum trace-back time of 1year, was defined as being at risk of cluster formation. We monitored each iGAS case at risk for a minimum of 1year to identify any cluster formation event, defined as the detection of a subsequent iGAS case clustered with the case at risk. We used the Kaplan-Meier method to estimate the cumulative incidence of cluster formation events over time. We used Cox regression to assess associations between features of cases at risk upon detection and subsequent cluster formation. We developed a random survival forest machine-learning model based on a derivation cohort (random selection of 50% of cases at risk) to predict cluster formation risk. This model was validated using a validation cohort consisting of the remaining 50%of cases at risk. We identified 2764iGAS cases at risk from 2016to 2018, of which 656 (24%) formed genomic clusters by the end of 2019. Overall, the cumulative incidence of cluster formation was 0·057 (95% CI 0·048-0·066) at 30days after detection, 0·12 (0·11-0·13) at 90days after detection, and 0·16 (0·15-0·18) at 180days after detection. Ahigher risk of cluster formation was associated with emm type (adjusted hazard ratio as compared with emm89 was 2·37 [95% CI 1·71-3·30] for emm1, 2·72 [1·82-4·06] for emm3, 2·28 [1·49-3·51] for emm6, 1·47 [1·05-2·06] for emm12, and 2·21 [1·38-3·56] for emm92), homelessness (1·42 [1·01-1·99]), injection drug use (2·08 [1·59-2·72]), residence in a long-term care facility (1·78[1·29-2·45]), and the autumn-winter season (1·34 [1·14-1·57]) in multivariable Cox regression analysis. The machine-learning model stratified the validation cohort (n=1382) into groups at low (n=370), moderate (n=738), and high (n=274) risk. The 90-day risk of cluster formation was 0·03 (95% CI 0·01-0·05) for the group at low risk, 0·10(0·08-0·13) for the group at moderate risk, and 0·21 (0·17-0·25) for the group at high risk. These results were consistent with the cross-validation outcomes in the derivation cohort. Using population-based surveillance data, we found that pathogen, host, and environment factors of iGAS cases were associated with increased likelihood of subsequent genomic cluster formation. Groups at high risk were consistently identified by a predictive model which could inform prevention strategies, although future work to refine the model, incorporating other potential risk factors such as host contact patterns and immunity to GAS, is needed to improve its predictive performance. Centers for Disease Control and Prevention.

Ranolazine in chronic total occlusion percutaneous coronary intervention.

Ranolazine is an anti-anginal medication given to patients with chronic angina and persistent symptoms despite medical therapy. We examined 11 491 chronic total occlusion (CTO) percutaneous coronary interventions (PCI) that were performed at 41 US and non-US centers between 2012 and 2023 in the PROGRESS-CTO Registry. Patients on ranolazine at baseline had more comorbidities, more complex lesions, lower procedural and technical success (based on univariable but not multivariable analysis), and higher incidence of major adverse cardiac events (MACE) (on both univariable and multivariable analysis).

Intravascular Lithotripsy versus Rotational Atherectomy in Coronary Chronic Total Occlusions: Analysis from the PROGRESS-CTO registry

There is limited comparative data on the use of plaque modification devices during chronic total occlusion (CTO) percutaneous coronary intervention (PCI). We compared intravascular lithotripsy (IVL) with rotational atherectomy (RA) for lesion preparation in patients who underwent CTO PCI across 50 US and non-US centers from 2019 to 2024. Among 15,690 patients who underwent CTO PCI during the study period, 436 (2.78%) underwent IVL and 381 (2.45%) RA. Patients treated with IVL had more comorbidities and more complex CTO lesions. Antegrade wiring was the most commonly used initial and successful crossing strategy for lesions treated with both IVL and RA, although the retrograde approach was more frequently employed in IVL cases. Procedure and fluoroscopy times, as well as air kerma radiation doses and contrast volumes, were higher in patients treated with RA compared with IVL. There were no significant differences between the groups in technical success (97.2% vs. 95.3%, p=0.20), procedural success (94.7% vs. 91.8%, p=0.14), and in-hospital major adverse cardiac events (MACE) (3.0 % vs. 4.2%, p=0.47). However, coronary perforations were more frequent in patients undergoing RA (9.5% vs. 3.2%, p<0.001). Multivariable logistic regression analysis revealed that IVL compared with RA was not independently associated with technical success, procedural success, or in-hospital MACE. In patients undergoing CTO PCI, IVL is associated with similar in-hospital MACE, technical success, and procedural success, but lower incidence of coronary perforation, compared with RA.

Development and validation of a deep learning model for detecting signs of tuberculosis on chest radiographs among US-bound immigrants and refugees.

Immigrants and refugees seeking admission to the United States must first undergo an overseas medical exam, overseen by the US Centers for Disease Control and Prevention (CDC), during which all persons ≥15 years old receive a chest x-ray to look for signs of tuberculosis. Although individual screening sites often implement quality control (QC) programs to ensure radiographs are interpreted correctly, the CDC does not currently have a method for conducting similar QC reviews at scale. We obtained digitized chest radiographs collected as part of the overseas immigration medical exam. Using radiographs from applicants 15 years old and older, we trained deep learning models to perform three tasks: identifying abnormal radiographs; identifying abnormal radiographs suggestive of tuberculosis; and identifying the specific findings (e.g., cavities or infiltrates) in abnormal radiographs. We then evaluated the models on both internal and external testing datasets, focusing on two classes of performance metrics: individual-level metrics, like sensitivity and specificity, and sample-level metrics, like accuracy in predicting the prevalence of abnormal radiographs. A total of 152,012 images (one image per applicant; mean applicant age 39 years) were used for model training. On our internal test dataset, our models performed well both in identifying abnormalities suggestive of TB (area under the curve [AUC] of 0.97; 95% confidence interval [CI]: 0.95, 0.98) and in estimating sample-level counts of the same (-2% absolute percentage error; 95% CIC: -8%, 6%). On the external test datasets, our models performed similarly well in identifying both generic abnormalities (AUCs ranging from 0.89 to 0.92) and those suggestive of TB (AUCs from 0.94 to 0.99). This performance was consistent across metrics, including those based on thresholded class predictions, like sensitivity, specificity, and F1 score. Strong performance relative to high-quality radiological reference standards across a variety of datasets suggests our models may make reliable tools for supporting chest radiography QC activities at CDC.