bluuebunny/crossref_metadata_2025 huggingface dataset:
624 DEALING WITH THE UNKNOWN: A STRANGE CASE OF RECURRENT FEVER
Authors: Brugiatelli Leonardo , Coretti Francesca , Alfieri Michele , Bastianoni Gianmarco , Paolini Federico , Coraducci Francesca , Belleggia Sara , Torselletti Lorenzo , Barbarossa Alessandro , Ciliberti Giuseppe , Principi Samuele , Di Noto Giorgio , Lanari Antonella , Giovagnoli Andrea , Tavio Marcello , Stronati Giulia , Russo Antonio Dello , Guerra Federico
Published: December 2022

Blood culture negative endocarditis (BCNE) accounts for 5-10% of all cases of endocarditis. The most common cause of this outcome is initiation of antibiotics prior to cultures. The second most common etiology of negative blood culture is infection secondary to intracellular organisms, which require specific serological tests to be detected. Less frequently, the cause BCNE is noninfectious endocarditis. In this case, it could be secondary to systemic inflammatory diseases or malignancies.

We present the case of a 64-year-old male who presented to his physician complaining of fever, malaise and generalized weakness. He was treated with oral antibiotics and with evidence of initial improvement, but after a few days the fever recurred. His past medical history was significant for cardiac surgery: he had an aortic bioprosthesis implanted for severe regurgitation secondary to left coronary cusp prolapse. Furthermore, he underwent mitral and tricuspid valve annuloplasty for severe regurgitation secondary to diffuse prolapse of these valves.

After recurrence of the fever, he presented to his local hospital. A CT scan was executed and showed left basal lobe hypoattenuation. Given the context, this finding led to a diagnosis of community-acquired pneumonia. He was then treated accordingly and improved. A few days later, the fever returned, and he went back to his local hospital. This time he was visited by a cardiologist, and a transthoracic echocardiogram showed the presence of a vegetation adherent to the aortic bioprosthetic valve. Revising the initial CT scan, the lobar consolidation initially seen was interpreted retrospectively as an atelectasis. On that same day, due to the presence of a painful red eye, the patient was visited by an ophthalmologist. Retinal examination revealed the presence of lesions strongly suggestive of fungal endophthalmitis.

Considering these results, fungal endocarditis was suspected. In view of the patient's complexity and the need for a cardiac surgery, the patient was transferred to our hospital and, after performing blood cultures to identify the pathogen, immediately started on an empirical broad-spectrum antibiotic and antifungal therapy. On admission a cerebral CT scan showed the presence of asymptomatic cerebral septic emboli. Due to the presence of cerebral lesions deemed at high hemorrhagic risk, no immediate surgical indication was posed, despite the suspicion of fungal endocarditis. Fortunately, the patient responded to medical treatment alone. However, blood cultures never revealed the presence of a defined pathogen. Therefore, the final diagnosis was that of blood culture negative endocarditis.
959 AN UNEXPECTED DIAGNOSIS BY ECHOCARDIOGRAPHY: APPLICATION IN CLINICAL PRACTICE
Authors: De Luca Valeria Maria , Antonelli Giorgio , Cammalleri Valeria , Carpenito Myriam , Mega Simona , Caricato Marco , Andrisani Gianluca , Quattrocchi Carlo Cosimo , Grigioni Francesco , Ussia Gian Paolo
Published: December 2022

A carcinoid tumore is a rare neuroendocrinologic malignancy that commonly origins from enterochromaffin or Kulchitsky cells in the gastrointestinal tract and secretes bioactive molecules in blood. Up to 60% of patients with carcinoid tumors have cardiac involvement, often on the right-sided heart valves (typically the tricuspid valve and the pulmonic valve).

A 66 year old woman was admitted to hospital with congestive heart failure, chronic diarrhea and weight loss. A contrast-enhanced computed tomography scan of the liver showed multiple masses (the largest 70 mm×45mm) compatible with metastases. A transthoracic echocardiogram showed dilatation of right sections of the heart with severe tricuspid regurgitation (RV 64 ml/beat, ERO 1 cmq) and mild pulmonary valve stenosis (Peak gradient 13 mmHg). Patient's aortic and mitral valves were normal in structure and function. The EKG revealed low-voltage QRS complexes of all leads, unspecific ST segment changes and sinusal rhythm. The blood tests showed a significant increase in chromogranin A (17670 ng/ml) and enolase; a 24-hour urine collection showed a total output of 5-hydroxyindoleacetic acid eleveted. A biopsy of the liver with immunostaining for chromogranin and synaptophysin were strongly positive and confirmed the diagnosis of metastatic carcinoid syndrome (grade 1, cells CDX2 positive).

The echocardiographic findings of carcinoid heart disease is drumstick-like, rigid, and shortened leaflets with a visible regurgitant orifice, causing torrential tricuspid regurgitation. The pulmonic valve presents more frequently valvular stenosis.

A combination of biomarkers and cardiac imaging is useful in screening and diagnosis of carcinoid heart involvement in patients with carcinoid syndrome. The management of carcinoid heart disease is hardful and requires a multidisciplinary approach, medical and surgical treatment, for optimized care.
943 THE RIGHT VENTRICULAR-ARTERIAL COUPLING AS AN INDICATOR OF PROGNOSIS IN PATIENTS WITH FUNCTIONAL MITRAL REGURGITATION UNDERGOING TRANSCATHETER “EDGE-TO-EDGE“ VALVE REPAIR
Authors: Lucchino Alessandro , Polimeni Alberto , Mongiardo Annalisa , Spaccarotella Carmen , Messina Chiara , Vizzari Francesca , Velato Letizia , Di Costanzo Assunta , Durante Pierfrancesco , Estévez-loureiro Rodrigo , D´ascenzo Fabrizio , Indolfi Ciro
Published: December 2022

Aims

Patients affected by severe functional Mitral Regurgitation (MR) complaining symptoms despite optimal medical therapy should undergo intervention. When the surgery, the gold standard, is not indicated due to high surgical risk, the transcatheter edge-to-edge repair (TEER) should be considered, if feasible. In patients undergoing TEER, the clinical outcome is not always optimal and strongly correlates to the patient's clinical conditions, so a correct selection of the patients is essential. In this regard, some studies have evaluated the RV-PA coupling as an important predictor of outcome in patients with Heart Failure (HF). In clinical practice, RV-pulmonary artery (PA) coupling could be estimated in a non-invasive way through the relationship between TAPSE (systolic excursion of the annular plane of the tricuspid valve) /PAPs (systolic pressure of the pulmonary artery) ratio that gives information about the state of contractility and adaptability to the load of the RV. In this study, we sought to evaluate how the TAPSE /PAPs ratio at baseline may improve prognostic stratification in patients undergoing TEER with the MitraClip system.

Methods and Results

Data from 236 patients with symptomatic, moderate to severe functional MR, subjected to implantation of MitraClip between March 2012 and June 2021, were obtained from the University's MITRA-CTV, multicenter observational register comprising data from the Magna Graecia University of Catanzaro (Italy), the University of Turin (Italy) and the University of Vigo (Spain). The median follow-up was 686 days (IQR 393-1131 days), with a 1-year follow-up in 224 of 236 (95%) patients. We divided the population into two groups based on the median value of the ratio TAPSE / PAPs ≤ 0.35 and TAPSE / PAPs> 0.35. The primary endpoint of this study includes Re-hospitalization for HF and Death from all causes at one-year follow-up. At Cox regression analysis, Hospital stay> 10 days (HR 1.67, 95% CI [1.03-2.77], p = 0.039) and the TAPSE / PAPs ratio ≤ 0.35 (HR1.58, 95% CI [1, 01-2.48], p = 0.0488) independently increased the risk of the primary endpoint at long-term follow-up. At Kaplan Meier analysis, a TAPSE / PAPs ratio of ≤ 0.35 was related to an increased incidence of the primary endpoint of Rehospitalization for HF and Death (HR 1.54, 95% CI [ 1-2.41], p = 0.0464).

Conclusion

In our study, the right ventricular-arterial coupling, estimated through TAPSE/PAPs Ratio, was identified as a predictor of outcome in patients with severe functional MR undergoing TEER.
763 ACTIVATION OF SIRT1 ATTENUATES VASCULAR DYSFUNCTION AND THROMBOSIS IN MTHFR DEFICIENCY
Authors: Carrizzo Albino , Iside Concetta , Nebbioso Angela , Carafa Vincenzo , Damato Antonio , Ciccarelli Michele , Venturini Eleonora , Di Pietro Paola , Trimarco Bruno , Selleri Carmine , Altucci Lucia , Vecchione Carmine
Published: December 2022

Beyond well-assessed risk factors, cardiovascular events could be also associated with the presence of epigenetic and genetic alterations, such as the methylenetetrahydrofolate-reductase (MTHFR) C677T polymorphism. This gene variant is related to increased circulating levels of homocysteine (Hcy) and cardiovascular risk. However, heterozygous carriers have an augmented risk of cardiovascular accidents independently from normal Hcy levels, suggesting the presence of additional deregulated processes in MTHFR C677T carriers. Here we hypothesize that targeting Sirtuin 1 (SIRT1) could be an alternative mechanism to control the cardiovascular risk associated to MTHFR deficiency condition.

Flow Mediated Dilatation (FMD) and light transmission aggregometry assay were performed in subjects carrying MTHFR C677T allele after administration of resveratrol, the most powerful natural clinical usable compound that owns SIRT1 activating properties. MTHFR C677T carriers with normal Hcy levels revealed endothelial dysfunction and enhanced platelet aggregation associated with SIRT1 downregulation. SIRT1 activity stimulation by resveratrol intake was able to override these abnormalities without affecting Hcy levels.

Impaired endothelial function, bleeding time, and wire-induced thrombus formation were rescued in a heterozygous Mthfr-deficient (Mthfr+/-) mouse model after resveratrol treatment. Using a cell-based high-throughput multiplexed screening (HTS) assay, a novel selective synthetic SIRT1 activator, namely ISIDE11, was identified. Ex vivo and in vivo treatment of Mthfr+/- mice with ISIDE11 rescues endothelial vasorelaxation and reduces wire-induced thrombus formation, effects that were abolished by SIRT1 inhibitor. Moreover, platelets from MTHFR C677T allele carriers treated with ISIDE11 showed normalization of their typical hyper-reactivity.

These results candidate SIRT1 activation as a new therapeutic strategy to contain cardio and cerebrovascular events in MTHFR carriers.
719 CIRCULATING SORTILIN LEVELS ARE INCREASED IN PATIENTS RECEIVING LONG-TERM WARFARIN AND ITS INHIBITION ATTENUATES WARFARIN-INDUCED VASCULAR CALCIFICATION
Authors: Di Pietro Paola , Abate Angela Carmelita , Rusciano Maria Rosaria , Visco Valeria , Izzo Carmine , Iacoviello Licia , Toni Anna Laura , Ciccarelli Michele , Carrizzo Albino , Vecchione Carmine
Published: December 2022

Long-term use of the vitamin K antagonist (VKA) warfarin, has been shown to accelerate vascular and valvular calcification both in rodents and in humans. Increasing evidence suggests that vascular endothelium contributes to calcification via endothelial-mesenchymal transition (EndMT). However, additional research is warranted to elucidate the signaling mechanisms involved. In the last decade, a prominent role for sortilin has been demonstrated in cardiovascular calcification. Moreover, we recently demonstrated that the increase of sortilin in the endothelium promotes endothelial dysfunction, a known initiator of EndMT.

Thus, we aim to investigate a potential contribution of sortilin in vascular calcification induced by warfarin. For this purpose, human endothelial cells and aortic rings from wild type C57BL/6J mice were cultured in promineralization medium in the presence of therapeutic levels of warfarin. Plasma sortilin and calcium levels were measured in 19 patients under VKA therapy who were stratified into short-term (3-12 months) or long-term group (24-45 months) based on VKA treatment duration.

Increased protein expression of sortilin was found both in the endothelial and in the medial smooth muscle layers of aortic rings. Sortilin immunostaining was found to co-localize with α-SMA in the endothelium of warfarin-treated aortic rings, a hallmark of EndMT. Interestingly, pharmacological inhibition of sortilin with AF38469 reduced calcification and prevented loss of expression of the endothelial marker von Willebrand Factor (vWF) induced by warfarin treatment in human endothelial cells and mouse aortas.

Finally, along with elevated plasma calcium levels, patients receiving long-term VKA showed increased circulating sortilin levels when compared to short term VKA-treated patients.

Our data provide evidence for a potential role for endothelial-derived sortilin in regulating vascular calcification promoted by warfarin, and suggest that targeting circulating sortilin may be beneficial for the prevention of warfarin-associated cardiovascular calcification.
734 APHASIC AORTITIS - A CASE REPORT
Authors: Berghi Razvan , Gonano Nicola , Del Mestre Eva , Pagura Linda , Tomietto Paola , Franzese Ilaria , Mazzaro Enzo , Merlo Marco , Sinagra Gianfranco
Published: December 2022

A 66yo man, without previous cardiological history, 3-month history of asthenia and left leg claudication, presence of tibial painless nodular lesions, was admitted at our emergency department in the clinical context of an acute aortic syndrome with chest and interscapular pain, fluctuating systemic BP (215/90 ←→ 90/60 mmHg) ​​and 60 mmHg pressure gradient between the arms. EKG documented diffuse negative T waves. Echocardiography revealed normal biventricular morphology and function and normal valve system. TC angiography documented a dilated aortic root (46mm), diffuse thickening of the aortic walls from the valvular plane (8mm), with involvement of the coronary and epiaortic arteries (50% stenosis of left subclavian artery), extended up to the aortic bifurcation to affect the common iliac arteries. Blood chemistry showed high C-reactive protein levels (29 mg/L; n.v. <5 mg/L) and low troponin levels. In the suspicion of an aortic wall hematoma, the patient was rushed to the OR with evidence of a lardaceous-looking aorta and free from wall hematomas. Surgery was stopped. Histological sample of left inguinal artery showed diffuse wall sclerosis and rare intramural lymphocyte infiltration. PET-CT showed an increased metabolism of the aortic walls. On the second postoperative day, the patient developed fluctuating aphasia aggravated by orthostatic position and arterial hypotension. In the suspicion of TIA, CT angiography was performed and showed no acute brain lesions, but a critical stenosis of the right carotid bifurcation, a right vertebral artery occlusion and a left internal carotid subocclusion. DAPT (clopidogrel + aspirin) was initiated. Blood chemistry showed normal WBC count, elevated C-reactive protein (133 mg/L; n.v. < 5 mg/L) and erythrocyte sedimentation rate (90 mm/h; n.v. < 35 mm/h). Blood and urine cultures, bacterial serology (syphilis, tubercolosis), viral serology (HBV, HCV, HIV) and autoantibodies tested (ANA, ENA, ANCA, MPO, PR3) resulted negative. In the context of a great vessel arteritis, IV methylprednisolone was introduced with clinical and biochemical response (C-reactive Protein 10 mg/L). MRI on day 10 demonstrated the presence of two cerebral subacute ischemic lesions with hemorrhagic infarction. Aspirin was discontinued. In suspicion of Takayasu arteritis, methotrexate was initiated with clinical benefit. Takayasu arteritis has an incidence of 2.6/1 million, female:male 8:1 and the age of onset is usually between 15 and 30 years. The cause is unknown. It can manifest as an acute aortic syndrome. It is important to be aware of this disease and to consider it in clinically ambiguous cases like this one.
676 A PITFALL IN ECHOGRAPHIC DIAGNOSIS OF ABDOMINAL AORTIC ANEURYSM: WHEN PARA-AORTIC LYMPH NODES REQUIRE ATTENTION
Authors: Natale Francesco , Loffredo Francesco , Molinari Riccardo , Covino Simona , Alfieri Roberta , Altobelli Ippolita , Pezzullo Enrica , Cimmino Giovanni
Published: December 2022

Image focus

A 65-year-old women was scheduled for coronary angiography during the pre-surgery evaluation because of an abdominal aortic aneurysm (AAA) detected at ultrasound (Figure). The patient referred worsening dyspnoea and asthenia in the last few months, associated with atypical chest pain. Because of these symptoms and taking into account that AAA patients are at very high cardiovascular risk, exclusion of coronary artery disease seemed appropriate. At admission, patient showed enlarged lymph nodes at cervical and inguinal region. In the suspicion of a malignant cancer, a contrast enhanced computed tomography was scheduled, showing an increase in para-aortic, inguinal, cervical and axillary lymph nodes size in absence of the AAA (Figure). After blood tests and an haematologic consultation, a final diagnosis of chronic myeloid leukaemia was made.

The Echo-colour Doppler is the first line imaging test for the diagnosis of AAA. However, in some cases it might be not sufficient. Para-aortic lymphadenopathy should be considered as a possible pitfall in the differential diagnosis of abdominal aortic aneurysm.
Association of genetically predicted lipid traits and lipid-modifying targets with heart failure
Authors: Xiao Jun , Ji Jianguang , Zhang Naiqi , Yang Xi , Chen Keyuan , Chen Liangwan , Huang Wuqing
Published: December 2022

Aims

To assess the association of genetically predicted lipid traits and lipid-modification via licensed or investigational targets with heart failure (HF).

Methods and results

Two-sample Mendelian randomization (MR) study was conducted using summary-level genome-wide association studies (GWASs) from UK Biobank and HERMES Consortium. Genetic variants obtained from UK Biobank GWAS data were selected as instrumental variables to predict the level of lipid traits [LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (ApoB), and apolipoprotein AI (ApoAI)] and lipid-modifying effect of eight drug targets [HMGCR, PCSK9, NPC1L1, PPARA, lipoprotein lipase (LPL), ANGPTL3, APOC3, and cholesteryl ester transfer protein (CETP)]. In this study, we observed that genetically predicted LDL-C, TG, HDL-C or ApoB were significantly related to HF, which were mainly mediated by coronary heart disease (CHD). Drug target MR analyses identified PCSK9, CETP, and LPL as potential targets to prevent HF. The genetic proxy of LDL-C and ApoB increase modified by PCSK9 showed similar evidence in increasing risk of HF (PLDL-C = 1.27*10−4; PApoB = 1.94*10−4); CETP played a role in HF risk via modifying all investigational lipid traits with the strongest evidence though ApoB (P = 5.87*10−6); LPL exerted effects on HF via modifying most lipid traits with the strongest evidence observed via modifying TG (P = 3.73*10−12).

Conclusion

This two-sample MR study provided genetic evidence of the associations between lipid traits and HF risk, which were mostly mediated by CHD. Besides, drug target MR studies indicated that PCSK9 inhibition, CETP inhibition, and LPL activation were effective in HF reduction.
Prevalence and concordance of oral and genital HPV by sexual orientation among US men
Authors: Sonawane Kalyani , Shyu Shiang Shiuan , Damgacioglu Haluk , Li Ruosha , Nyitray Alan G , Deshmukh Ashish A
Published: December 2022

The objective of our study was to describe oral and genital human papillomavirus (HPV) infection prevalence and concordance by sexual orientation among US men using a nationally representative sample. We conducted a retrospective cross-sectional analysis of the 2013-2016 National Health and Nutrition Examination Survey. The survey conducts a physical examination and collects oral rinse and genital swab specimens; demographic and health behaviors are self-reported. We used descriptive statistics and multivariate regression models to estimate HPV infection prevalence and the likelihood of HPV infection, respectively. All analyses were adjusted for National Health and Nutrition Examination Survey design and weights, and statistical significance was tested at a 2-sided P value of less than .05. Men who have sex with men had a statistically significantly higher prevalence of oral HPV (high-risk, 9-valent, 4-valent, and HPV 16 and 18), genital HPV (9-valent, 4-valent, and HPV 16 and 18), and concordant oral and genital HPV (high-risk and 9-valent) infections compared with heterosexual men. Improved HPV prevention among men is needed.
Integrating Geriatric Assessment Measures into National Cancer Institute Clinical Trials
Authors: Magnuson Allison , Van der Walde Noam , McKoy June M , Wildes Tanya M , Wong Melisa L , Le-Rademacher Jennifer , Little Richard F , Klepin Heidi D
Published: December 2022

To improve the care of older adults with cancer, the traditional approach to clinical trial design needs to be reconsidered. Older adults are underrepresented in clinical trials with limited or no information on geriatric-specific factors, such as cognition or comorbidities. To address this knowledge gap and increase relevance of therapeutic clinical trial results to the real-life population, integration of aspects relevant to older adults is needed in oncology clinical trials. Geriatric assessment (GA) is a multidimensional tool comprising validated measures assessing specific health domains that are more frequently affected in older adults, including aspects related to physical function, comorbidity, medication use (polypharmacy), cognitive and psychological status, social support, and nutritional status. There are several mechanisms for incorporating either the full GA or specific GA measures into oncology therapeutic clinical trials to contribute to the overarching goal of the trial. Mechanisms include utilizing GA measures to better characterize the trial population, define trial eligibility, allocate treatment receipt within the context of the trial, develop predictive models for treatment outcomes, guide supportive care strategies, personalize care delivery, and assess longitudinal changes in GA domains. The objective of this manuscript is to review how GA measures can contribute to the overall goal of a clinical trial, to provide a framework to guide the selection and integration of GA measures into clinical trial design, and ultimately enable accrual of older adults to clinical trials by facilitating the design of trials tailored to older adults treated in clinical practice.
Workers’ Responses to Paternalism in British Factory-Based Events (1840–1860)
Authors: Moine Fabienne
Published: December 2022

Opportunities to celebrate the success of the firm, its leaders and, by extension, its employees, were numerous in the mid-Victorian period: banquets, dinners and outings, annual gatherings, pleasure trips and excursions, processions around the mills, or ceremonies directly related with the employer’s family. The purpose of this paper is to analyse some of these large communal events organized in textile mills in order to better understand the practices and meanings of paternalism on the side of the workers. The first part of this study of paternalism ‘from below’ explores the feudal structure of paternalism and the complex role played by deference in the large communal events organized in textile factories. The second part, about the large social events organized by captains of industry turned philanthropists, Titus Salt and Samuel Courtauld, examines the display of power in ‘the theatre of paternalism’ and raises the question of a possible circumvention of the paternalistic model on the part of workers. The last part is about the specificities of laudatory poems praising captains of industry and thanking them for the outings and celebrations they organized for their employees. It analyses how this specific poetical subgenre offers a space for renegotiation of paternalism and social boundaries.
86. Antibiotic-resistant gram-negative bacterial infections among persons with or without a prior positive test for SARS-CoV-2 in 10 U.S. sites, 2020
Authors: Bulens Sandra N , Grass Julian E , Duffy Nadezhda , Tola Jigsa , Jacob Jesse T , Smith Gillian , Vaeth Elisabeth , Dumyati Ghinwa , Looi Hsioa Che , Phipps Erin C , Flores Kristina , Wilson Christopher , Muleta Daniel , Czaja Christopher A , Driscoll Jennifer , Lynfield Ruth , O'Malley Sean M , Maloney Meghan , Stabach Nicole , Nadle Joelle , Pierce Rebecca , Hertzel Heather , Guh Alice
Published: December 2022

Background

The Centers for Disease Control and Prevention’s Emerging Infections Program (EIP) conducts active laboratory- and population-based surveillance for carbapenem-resistant Enterobacterales (CRE), extended spectrum beta-lactamase-producing Enterobacterales (ESBL-E), and carbapenem-resistant Acinetobacter baumannii (CRAB) in 10 U.S. sites. To describe the impact of the COVID-19 pandemic on the epidemiology of these antibiotic-resistant gram-negative bacteria (AR-GNB), we assessed characteristics of AR-GNB patients with and without a prior SARS-CoV-2 positive (SC2+) viral test.

Methods

In 2020 among EIP catchment-area residents, an incident CRAB or CRE case was defined as the first isolation of A. baumannii complex, Escherichia coli, Enterobacter cloacae complex, Klebsiella aerogenes, K. oxytoca, K. pneumonia, or K. variicola in a 30-day period resistant to ≥1 carbapenem (excluding ertapenem for CRAB) from a normally sterile site or urine. An incident ESBL-E case was defined as the first isolation of E. coli, K. pneumonia, or K. oxytoca in a 30-day period resistant to any third-generation cephalosporin and non-resistant to all carbapenems from a normally sterile site or urine. Patient charts were reviewed.

Results

Of 3904 AR-GNB cases with data available, 163 (4%) had a prior SC2+ test (85 ESBL-E, 70 CRE, and 8 CRAB). Median time from the most recent SC2+ test to AR-GNB culture date was 20 days (IQR 1–48 days). AR-GNB cases with a SC2+ test versus those without were more likely to be Black, non-Hispanic than another race/ethnicity (31% vs 15%; P< 0.0001), aged ≥65 years (62% vs 52%; P=0.0139), and to have prior healthcare exposures (63% vs 49%; P=0.0003) and indwelling devices (51% vs 28%; P< 0.0001). They were also more likely to have bacteremia (24% vs 11%; P< 0.0001), pneumonia (6% vs 1%; P< 0.0001) and be hospitalized around the time of their AR-GNB culture (67% vs 36%; P< 0.0001); median time from SC2+ test to hospital admission was 0.5 day (IQR 0–29.5 days).

Conclusion

AR-GNB infections preceded by a SC2+ test were rare but more severe and associated with more healthcare risk factors. This underscores the need for continued infection prevention and control practices and monitoring of these infections during the COVID-19 pandemic.

Disclosures

Ghinwa Dumyati, MD, Pfizer: Grant/Research Support.
92. Incidence of Adenovirus Respiratory Infection and Coinfection in a Longitudinal Birth Cohort
Authors: Gailani Adam E , Teoh Zheyi , Conrey Shannon C , Burke Rachel M , Cline Allison R , Killerby Marie E , Lu Xiaoyan , Mattison Claire , McNeal Monica , Morrow Ardythe L , Payne Daniel C , Staat Mary A
Published: December 2022

Background

Adenoviruses (AdVs) are a common cause of acute respiratory illness (ARI) in children and are often detected with other viruses (coinfection). However, the community incidence of AdV infections is poorly understood due to a lack of prospective studies outside the hospital setting. Here, we aim to characterize respiratory AdV infections and coinfections in a prospective birth cohort of children.

Methods

The PREVAIL cohort is a CDC-funded, 2-year birth cohort, conducted from 2017–2020 in Cincinnati, OH. ARI was defined as the presence of cough or fever identified with weekly maternal text surveys and medical chart review. Mid-turbinate nasal swabs were collected weekly. Swabs were tested using Luminex Respiratory Pathogen Panel. AdV infection was defined as a swab positive for AdV and included subsequent positives < 30 days apart. Coinfection was defined as detection of any other virus(es) during an AdV infection. Children who submitted at least 70% of weekly samples were included in our analysis.

Results

101 children met inclusion criteria, representing 165 child-years. 137 distinct AdV infections were identified (incidence 0.84 infections per child year), with 98 (97%) children having ≥1 AdV infection. Only 40% (n=55) of AdV infections were symptomatic. Of those with symptomatic infections, 51% (n=28) sought medical care, with 42% (n=23) presenting to a primary care provider and 9% (n=5) resulting in an ED visit or hospital admission. Coinfections were detected in 67% (n=92) of AdV infections, with 45% (n=62) coinfected with 1 virus, 19% (n=26) with 2 viruses, and 3% (n=4) with ≥3 viruses. 77% of coinfections (n=71) were rhino/enterovirus. The number of coinfections or the specific coinfection virus was not associated with an increase in symptom prevalence or symptom severity (all p > 0.05).

Viral Coinfection Frequency with Adenovirus Infection in the PREVAIL Cohort.

Adenovirus Infection and Coinfection in the PREVAIL Cohort.

Conclusion

In this cohort of healthy children, AdVs were a common cause of respiratory infection. Most infections were asymptomatic or resulted in mild symptoms. Two-thirds of AdV infections involved viral coinfections, but coinfection was not associated with more frequent or severe symptoms. Our findings suggest studies that only include symptomatic or hospitalized patients may overestimate AdVs disease severity.

Disclosures

All Authors: No reported disclosures.
737. Oral Antibiotic Stepdown Therapy for Uncomplicated Streptococcal
Authors: Loomis Jordan M , Mang Norman S , Ortwine Jessica , Prokesch Bonnie C , Wei Wenjing
Published: December 2022

Background

Streptococcus species are known pathogens in bloodstream infections (BSIs). Traditionally, BSIs are managed with intravenous (IV) antibiotics, however there is growing literature supporting oral (PO) antibiotics in BSIs as well as other invasive infections. Advantages to PO therapies include shortened hospital stay, reduced treatment costs, and avoidance of line-related complications. Currently, there is a paucity of data supporting the use of PO antibiotics in streptococcal BSIs.

Methods

This retrospective cohort study evaluated patients with streptococcal bacteremia between September 2019 to September 2021. Patients 18 and older were included if they had at least one positive blood culture for any Streptococcus species and excluded if BSI was polymicrobial, or treatment was for complicated BSI, identified by receipt of targeted therapy for ≥ 16 days, or source being endocarditis, osteomyelitis, or meningitis. Clinical outcomes were compared between patients who completed treatment with IV antibiotics verses those who completed with an PO stepdown regimen. The primary endpoint was clinical failure, which was a composite endpoint defined as BSI recurrence with the same pathogen and infection-related readmission within 30 days from completion of antibiotics.

Results

A total of 158 patients were included, with 77 (49%) receiving a full course of IV antibiotics and 81 (51%) receiving an PO antibiotic stepdown regimen. Clinical failure was not different between the IV antibiotics group versus the PO stepdown group, respectively (16% vs. 15%, odds ratio [OR] = 0.94; 95% confidence interval [CI], 0.40 to 2.25). No differences were observed in 30-day all-cause mortality. Patients that received PO antibiotic stepdown therapy had a significantly shorter hospital length of stay by 6 days (6 versus 12 days, p< 0.01).

Conclusion

Our results suggest that clinical cure with an PO stepdown regimen for uncomplicated streptococcal BSIs is comparable to IV antibiotics. The benefit of comparable efficacy in the setting of reduced length of stay and avoidance of central line placement for outpatient IV antibiotics should be considered when making treatment plans for patients with uncomplicated streptococcal BSIs.

Disclosures

All Authors: No reported disclosures.
752. Decreased Echinocandin Resistance among Candida glabrata over an Eleven-Year Period at a University Hospital
Authors: Raabe Nathan , Zhao Yanan , Paderu Padmaja , Shields Ryan K , Clancy Cornelius J , Nguyen Minh-Hong
Published: December 2022

Background

Invasive candidiasis (IC) is associated with significant morbidity and mortality. Echinocandins (ECH; caspofungin (CAS), micafungin (MFG), anidulafungin (AFG)) are first line therapy for IC. ECH resistance has emerged widely, most commonly among Candida glabrata. At some centers, > 10% of C. glabrata are ECH resistant. We reported ECH resistance in 8% of C. glabrata at our hospital from 2008–2014, which prompted stewardship strategies to limit prolonged ECH treatment courses. We evaluated trends of ECH resistance from Jan 2010-Dec 2020 among C. glabrata clinical isolates, and assayed isolates for FKS hot spot (HS) mutations.

Methods

We mined electronic medical records for ECH MIC data against C. glabrata clinical isolates at UPMC. We defined ECH resistance using Clinical and Laboratory Standards Institute clinical breakpoints. Isolates resistant to any ECH underwent FKS Sanger sequencing. Statistical analysis was performed using Stata.

Results

Overall CAS, AFG and MFG resistance rates among 516 isolates were 4%, 3%, and 2.5%, respectively. There was no significant difference in resistance rates between blood and non-blood sites (Table 1). There was a significant decrease in MFG resistance over the 12-year period (Fig 1). Time series regression analysis showed a decrease in rate of MFG resistance of 0.73% per year (p=.007). Trends for decreases in AFG and CAS resistance rates were also noted (p=.1 and p=.17). Similar analyses showed annual decreases in MFG MICs (0.019 μg/mL per year; p=.07). The average percentage of AFG resistant isolates was significantly lower in 2017–2020 than in 2012–2016 (p=.04); similar trends were evident for MFG (p=.07) and CAS (p=.08) (Fig 2). Sanger sequencing of FKS1/2 was performed for 27 isolates resistant to ≥1 ECH. Mutations were found in 44% (12/27) of isolates: 5 mutations in HS1 FKS1, 1 in HS2 FKS1, 5 in HS1 FKS2 and 1 in HS2 FKS2. Using both CAS and AFG MICs was most predictive of FKS mutations (Fig. 3).

Conclusion

ECH resistance among C. glabrata stabilized or decreased over 11-years at our hospital, in keeping with stewardship interventions to reduce prolonged use of ECHs. These results demonstrate that it is feasible to conserve ECH susceptibility.

Disclosures

Cornelius J. Clancy, MD, receives research funding paid to his institution from Astellas and Merck: Grant/Research Support|serves as an advisory Board member for Astellas, Cidara, and Scynexis, served on the advisory board for Merck, Qpex Biopharma, and Shionogi: Advisor/Consultant|Venatorx and Needham & Associates: Advisor/Consultant Minh-Hong Nguyen, MD, QPX: Grant/Research Support.
779. PIDS Featured Oral Abstract: High Beta Lactam Exposure in Neonates with Bloodstream Infection Associated with Intestinal Dysbiosis and Enterococcus spp. Abundance in the Gut Microbiome
Authors: Hendricks Hope , Weitkamp Jörn-Hendrik , Pakala Suman , Rajagopala Seesandra , Banerjee Ritu
Published: December 2022

Background

To characterize how antibiotic exposure impacts development and durability of intestinal dysbiosis and the acquisition of antibiotic resistance genes (ARGs) in the intestinal flora of premature infants in the Neonatal Intensive Care Unit (NICU), we established an infant gut microbiome biorepository (IGMB).

Methods

We performed prospective weekly stool collection in NICU patients meeting the following criteria: birthweight < 2000 g, postnatal age < 2 months and no diagnoses of congenital gut malformation or cyanotic heart disease. Cases were infants with bloodstream infections (BSI), defined as bacterial growth from blood culture; controls were infants with < 5 days of antibiotic exposure, no BSI nor necrotizing enterocolitis. We performed metagenomic analysis on 5–6 serial stool samples from each of the 10 cases and 10 controls (n= 100 stools). We used Wilcoxon rank sum tests for pairwise comparisons.

Results

From July 2021 to May 2022, 265 infants contributed 1,300 stool samples to the IGMB. In 7 of 8 BSI cases the causative pathogen was identified in the pre-BSI stool sample. Two more BSI cases did not have a pre-BSI stool sample. Microbiome species α-diversity increased with advancing postnatal age in controls but not in cases (Fig. 1). Among 6 cases with high beta lactam exposure ( >14 cumulative days by last stool collection), 3 had notable increases in the relative abundance of Enterococcus spp. (Fig. 2). Controls did not have similar trends in Enterococcus spp., but did have higher relative abundance of facultative anaerobes including Bifidobacterium, Lactobacillus, and Veillonella spp. (Fig. 3). Antibiotic resistance gene (ARG) abundance did not differ significantly between cases and controls.

Conclusion

Compared to controls, neonates with BSI have increased antibiotic intensity throughout their NICU admissions, reduction of microbial species diversity and overabundance of specific organisms in their gut microbiomes. We observed increased Enterococcus spp. prevalence with higher beta lactam exposure. ARG abundance did not differ between cases and controls. The clinical implications of this microbiome dysbiosis warrant further study.

Disclosures

Jörn-Hendrik Weitkamp, MD, Roche Diagnostics: Advisor/Consultant.
782. Infectious Complications of Lung Transplant for COVID-Associated Lung Injury (CALI)
Authors: Osborn Rebecca , Ison Michael G , Alamri Maha M
Published: December 2022

Background

More than 200 orthotopic lung transplants (OLT) have been performed in the United States for patients (pts) with severe CALI. While some outcomes have been reported to generally be good, we conducted this study to describe the infectious outcomes.

Methods

After IRB approval, a retrospective case review was conducted of pts at Northwestern Memorial Hospital who had undergone OLT for CALI between June 1, 2020 and January 31, 2022. Data was collected from our Enterprise Data Warehouse and primary chart review to describe pts demographics and epidemiology of infectious complications.

Results

35 OLTs were included (33 bilateral, 2 single lung; see Table 1). In the two weeks prior to transplant, 65.7% of pts were treated for bacterial, fungal, or mycobacterial infections (Table 2). Post-transplant, 32 (91.4%) of OLTs developed infections (Table 2), with most (28, 80%) developing pneumonia within 30 days of transplant. Five (14.3%) pts had airway complications, 7 (20%) pts required hemodialysis, and 3 (8.6%) pts died within one year of follow-up.

Conclusion

Infections remain a significant cause of morbidity post-OLT for CALI. Enhanced immunosuppression, long ICU stays post-tx, high rates of primary graft dysfunction and deconditioning likely contributed to this high rate of infection. A matched control group is being collected to compare these outcomes to other OLT pts.

Disclosures

Michael G. Ison, MD MS, GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support.
792. Predictive Value of Methicillin-Resistant Staphylococcus aureus (MRSA) PCR Nasal Swab for Invasive MRSA Infection in Critically Ill Pediatric Patients: A Promising Tool for Antimicrobial Stewardship
Authors: Crawford Lexi M , Hamdy Rana F , Pertsovskaya Vera , Zhang Anqing
Published: December 2022

Background

Patients admitted to the pediatric intensive care unit (PICU) are frequently evaluated for bacterial infections and initiated on antibiotic regimens that include a MRSA-active agent even though invasive MRSA infections are rare in this population. The MRSA PCR nasal swab (MRSA-PCR) is a non-invasive test for MRSA colonization that has been shown within adult ICUs to have a high negative predictive value (NPV), making it a potentially valuable tool for antimicrobial stewardship. This study evaluated the performance of the MRSA-PCR in predicting invasive MRSA infection in critically ill pediatric patients.

Methods

A retrospective cohort study was performed in a 44-bed PICU from January 2013 to December 2018 when it was protocol for all admissions to be screened with a MRSA-PCR. Patients who had both a MRSA-PCR and cultures obtained to evaluate for invasive infection within seven days were included in the study. Invasive MRSA infection was defined by the isolation of MRSA from clinical cultures along with infectious signs and symptoms. A random sample comprising 55% of the patient population was evaluated. We calculated sensitivity, specificity, positive predictive value (PPV) and NPV of the MRSA-PCR for confirmed invasive MRSA infection.

Results

Of the 4,410 patients reviewed, 1,961 patients met inclusion criteria (45% female, mean age 7.4 yrs. [birth-19.9 yrs.]). MRSA-PCR was positive in 13.5% of patients. Invasive MRSA infection was identified in 25 patients (2 blood, 19 respiratory, 2 soft tissue, 1 pleural fluid, and 1 urine culture) equaling 1.2% of encounters and an incidence rate of 1.1 case per 1,000 patient days. The MRSA-PCR demonstrated a PPV of 8.7% and a NPV of 99.8% (see table).

Conclusion

The MRSA-PCR has a poor PPV but a very high NPV for invasive MRSA infection in critically ill pediatric patients, a result that is congruent with what has been reported in the adult literature. The high NPV of the MRSA-PCR in this vulnerable patient population makes it a potentially powerful tool for antimicrobial stewardship. Creation of protocols to guide antimicrobial selection based on MRSA-PCR results may lead to a significant reduction in unnecessary antibiotic exposure, drug level monitoring, and patient risk of renal injury or adverse reactions.

Disclosures

All Authors: No reported disclosures.
793. Procalcitonin-guided Antibiotic Stewardship Oversight Reduces Antibiotic Use and Adverse Outcomes for Patients Admitted with Pneumonia, Results from a Real-world Randomized Controlled Trial in US Hospitals
Authors: Mansour Michael
Published: December 2022

Background

ProSAVE (NCT04158804) is the first prospective interventional RCT to address the effect of procalcitonin (PCT)-guidance in the setting of antimicrobial stewardship (ASP) oversight on clinical outcomes and antibiotics usage for patients admitted with pneumonia.

Methods

Analysis of the pilot cohort from a multicenter trial was conducted enrolling subjects admitted with pneumonia at three clinical sites (academic and community hospitals). Subjects meeting eligibility criteria were randomized 1:1 between the standard of care (SoC) versus PCT-guided ASP oversight (PCT arm); subjects were monitored daily by chart review for up to 30 days. An FDA-approved PCT algorithm was used to guide antimicrobial usage.

95 patients were enrolled as ITT of which 60 patients were assigned per-protocol who were adherent to the PCT algorithm (30 in SoC and 30 in the PCT arm). Primary study endpoints were antimicrobial usage and composite safety comprising readmission, death, intubation, septic shock, renal failure, and pneumonia complications such as empyema and abscess up to day 30.

Results

Baseline subject characteristics were similar between both arms; median age 73y (IQR: 62–86, heart disease (43% SoC vs. 40% PCT arm), and diabetes (23% SoC vs. 29% PCT arm). Early antimicrobial cessation by day 4 of hospitalization was achieved more often in the PCT arm as compared to SoC (ITT: SoC n=5, 11% vs. PCT arm n=14, 29%, p=0.045). In addition, antimicrobial prescription at discharge was lower in the intervention arm (ITT: SoC n=24, 51% vs. PCT arm n=15, 31%, p=0.08; similar and statistically significant efficacy for PP) (Fig 1, panel A). A substantial statistically significant improvement of safety was observed in the PCT arm compared to SoC (reduction by 18.3% (95%-CI: 2.3% – 36.3%) from 23.3% (11.9% – 41.1%, SoC) to 3.3% (0.8% – 16.7%, PCT arm) in PP, similar in ITT) (Fig 1, panel B). Readmission was the main driver for fewer safety events in the intervention arm (SoC 50% vs. PCT arm 33%).

Conclusion

In this pilot cohort of ProSAVE, the introduction of PCT-guided, ASP intervention to medical teams proved to be a successful aid for resourceful antibiotic management decisions resulting in shorter antibiotic durations and significantly lower adverse event rates.

Disclosures

Michael Mansour, MD, PhD, ThermoFisher Scientific: Grant/Research Support.
796. HIV transmission clusters among people who inject drugs in North Carolina, 2010 to 2021
Authors: Panichsillapakit Theppharit , Enders Kimberly , Greifinger Annalea C , Zhou Shuntai , Frost Simon , DPhil M A , Swanstrom Ronald , Eron Joseph J , Mobley Victoria , Samoff Erika , Dennis Ann
Published: December 2022

Background

The marked increase in injecting drug use (IDU) in the past decade presents concern for increased HIV transmission among people who inject drugs (PWID) and explosive outbreaks. Among statewide HIV molecular surveillance, we assessed demographic, clinical, and reported behavioral risk factors associated with HIV clusters involving PWID in North Carolina (NC).

Methods

Persons ≥ 13 years old with HIV-infection residing in NC with ≥ 1 partial pol sequence collected between April 2010 and December 2021 were included in the study. We used an automated cluster analysis pipeline to detect genetic clusters (nextHIV2), defined as ≥ 2 sequences with a pairwise genetic distance < 1.5%. Logistic regression was used to estimate the risk and adjusted odds ratios of the relationship between the demographic factors that were likely associated with HIV clustering. Graphics were generated using the R packages ggplot2 and igraph.

Results

Among 19,641 persons with a sequence, 1,611 were PWID. Of these, 347 (21.5%) PWID were members of 248 clusters involving a total of 2,083 persons (size ranged 2–104). Sixty-four clusters (25%) had ≥2 PWID, whereas 2 (1%) included at least 5 PWID. The most commonly injected drug among cluster members was methamphetamine (19%). Overall, in a univariate analysis, younger age, dual risks of male-to-male sex and IDU, having sex under the influence of drugs, recent IDU (past 12 months), acute HIV infection, higher viral loads and higher CD4 T-cell count at the time of HIV diagnosis were significantly associated with clustering PWID individuals (all P< 0.001). In multivariate analyses, only recent IDU and higher CD4 T-cell count at the time of HIV diagnosis were significantly associated with clustering (P< 0.01). In addition, the proportion of PWID in clusters increased from 11.2% in 2010–2013 to 28.5% in 2018–2021 (P< 0.001).

Nodes are colored by their reported PWID in darkred and reported non-PWID in blue.

Conclusion

We detected an increase in HIV genetic clusters among PWID in NC in recent years. Our results support the use of routine local molecular HIV surveillance to identify high priority clusters and offer prevention interventions for specific risk groups to prioritize limited public health resources.

Disclosures

Joseph J. Eron, MD, GSK: Advisor/Consultant|Merck: Advisor/Consultant.