Treatment Of High-risk Patients Research Articles

A Cardiovascular Disease Risk Score Model Based on High Contribution Characteristics

Cardiovascular disease (CVD) risk prediction shows great significance for disease diagnosis and treatment, especially early intervention for CVD, which has a direct impact on preventing and reducing adverse outcomes. In this paper, we collected clinical indicators and outcomes of 14,832 patients with cardiovascular disease in Shanxi, China, and proposed a cardiovascular disease risk prediction model, XGBH, based on key contributing characteristics to perform risk scoring of patients’ clinical outcomes. The XGBH risk prediction model had high accuracy, with a significant improvement compared to the baseline risk score (AUC = 0.80 vs. AUC = 0.65). At the same time, we found that with the addition of conventional biometric variables, the accuracy of the model’s CVD risk prediction would also be improved. Finally, we designed a simpler model to quantify disease risk based on only three questions answered by the patient, with only a modest reduction in accuracy (AUC = 0.79), and providing a valid risk assessment for CVD. Overall, our models may allow early-stage intervention in high-risk patients, as well as a cost-effective screening approach. Further prospective studies and studies in other populations are needed to assess the actual clinical effect of XGBH risk prediction models.

Osteoporoza

Osteoporosis is the most frequent metabolic bone disease. It is characterized by decreased bone strength and bone fractures and consequently decreased quality of life with increased morbidity and mortality. It affects the population of postmenopausal women and older people of both gender, but also patients with other primary diseases. Modern diagnostic procedures such as bone mineral density measurement, trabecular bone score (TBS) measurement, and fracture assessment risk score (FRAX) enable early diagnosis and treatment in high-risk patients. The complex etiology and pathophysiology of osteoporosis require secondary causes to be differentiated from primary osteoporosis before the most optimal treatment is initiated. The treatment should be personalized. Two methods of treatment are antiresorptive treatment aimed toward the inhibition of bone degradation and anabolic treatment with stimulation of new bone formation. Ideally, the prevention of fractures should be the treatment of choice, otherwise, prevention of new fractures and improvement of life is the therapeutic goal. Bisphosphonates are the first line antiresorptive treatment together with denosumab, a monoclonal human antibody against RANK ligand (receptor activator of nuclear factor kappa B). Teriparatide, an N-terminal parathormone fragment, is the dominant anabolic drug. Vitamin D deficiency is a widespread problem and contributes to bone mass decrement and increased risk for fractures. With further advancements in understanding the biology of bone tissue, new therapeutic agents are expected in the treatment of patients with osteoporosis.

PS-BPC02-1: PCSK-9-INHIBITOR THERAPY IMPROVES ENDOTHELIAL FUNCTION IN HIGH-RISK PATIENTS WITH CARDIOVASCULAR DISEASE

Background: Impaired endothelial function predicts cardiovascular events. The aim of this study was to analyse the effect of evolocumab on endothelial function in patients with cardiovascular disease and on obligatory statin therapy. Methods: This was a prospective, double-blinded, randomized, controlled, single center study (NCT03626831) including patients with cardiovascular disease (diagnosis of coronary artery disease, non-hemorrhagic stroke, transient ischemic attack or symptomatic peripheral artery disease) and treated with statins, similar to the inclusion criteria of the FOURIER study. Patients were consecutively randomized (1:1) to either evolocumab treatment (420 mg was administrated in monthly intervals, twice during the study) or placebo. All patients underwent examination of endothelial function at baseline, and after 1, 4 and 8 weeks of treatment by a semi-automatic high-resolution ultrasound system (UNEX EF 18G; Unex Co., Nagoya, Japan). Endothelial function parameter such as flow-mediated vasodilation (FMD; vasodilator responsiveness), low flow-mediated vasocontriction (L-FMC; vasoconstrictor responsiveness) and vasoactive range (VAR; total vasomotor responsiveness) were measured. Results: 103 patients with a mean age of 66.2 (±7.7) years and a mean LDL-cholesterol of 98.2 (±19.1) mg/dl completed the study. 83.5% of the study population was known to have coronary artery disease. Endothelial function parameter (VAR) increased after 8 weeks of treatment with evolocumab compared to baseline (p = 0.034), whereas there was no significant change at 1 and 4 weeks after treatment. Moreover, an improvement in VAR from baseline at week 8 was found with evolocumab compared to placebo (p = 0.045). In a subgroup analysis, in patients with age < 67 years, lower systolic blood pressure (< 125 mmHg) or higher baseline LDL-cholesterol (> 95 mg/dl), significant evolocumab treatment effect was found in VAR improvement (p = 0.006, p = 0.049 and p = 0.042, respectively) from baseline at week 8. No serious adverse event related to study medication occurred during the study. Conclusion: Our data indicate that endothelial function could be improved with evolocumab treatment in high-risk patients with preexisting cardiovascular disease and on statin therapy. Our results contribute to the mechanistic explanation why lower incidence of the cardiovascular composite endpoint has been demonstrated in the FOURIER study.

Staphylococcus aureus bacteriuria: implications and management.

Staphylococcus aureus is isolated in around 0.2%-4% of positive urinary cultures, more commonly in the contexts of long-term care, urological abnormalities and procedures, male sex, older age and comorbidities. Isolation may represent contamination, colonization, urinary tract infection or bacteraemic seeding from another site, and may be linked to S. aureus bacteraemia. However, there is little guidance on investigation and management of S. aureus bacteriuria. We performed a retrospective analysis of cases in our service, including clinical characteristics, investigations and treatment. Data were collected on all urine samples taken from adult patients over a 5-year period from which S. aureus was isolated. Detailed analysis including investigations and management was conducted in those collected over a 1-year period. From 511 patients, 668 urine cultures positive for S. aureus were identified; 6.5% of cases were positive for MRSA. Of 93 patients who had blood cultures taken, there were 6 cases of S. aureus bacteraemia, 4 of which were associated with urological instrumentation. Of 94 cases analysed in detail, 57% were treated with antibiotics, and 49% had repeat urine cultures. Factors associated with recurrence were urinary catheterization, urological abnormality, diabetes and inpatient status. Our experience does not support the routine taking of blood cultures or treatment of asymptomatic bacteriuria in well patients with S. aureus bacteriuria in this setting. However, repeat urine culture, and investigation and treatment of higher risk patients, for example, prior to bladder instrumentation, may be warranted. We propose a simple algorithm to guide clinicians.

Risk Factors and Prognosis of Carbapenem-Resistant Organism Colonization and Infection in Acute Cholangitis.

To identify the risk factors and prognosis of carbapenem-resistant organisms (CRO) in patients with acute cholangitis. This retrospective observational study was conducted to explore the risk factors and prognosis of CRO infection in 503 acute cholangitis patients diagnosed between July 2013 and January 2022 at the First Affiliated Hospital of Chongqing Medical University, who were divided into a CRO group and non-CRO group based on the presence or absence of CRO. Univariate, multivariate analyses, and the proportional hazards model were used to compare the risk factors and prognosis of CRO suffering in patients with acute cholangitis. We identified 35 patients colonized with CRO from 503 acute cholangitis patients. In the multivariate analysis, tumor (OR=7.09, 95% CI=1.11-45.30, P=0.038) and chronic kidney disease (OR=8.70, 95% CI=2.11-35.88, P=0.003) were ascertained as the risk factors of the occurrence on CRO infection under the background of acute cholangitis. CRO infection was identified as an independent risk factor for acute cholangitis patient death (HR=5.147, 95% CI=1.475-17.595, P=0.01) by Cox proportional-hazards regression. Tumor and chronic kidney disease may be risk factors for CRO infection. Patients diagnosed with acute cholangitis further infected with CRO had a poor prognosis and a more severe mortality. Active screening for CRO is expected to facilitate early prevention, diagnosis, and treatment of high-risk patients.

The Implementation of Preeclampsia Screening and Prevention (IMPRESS) Study

Preeclampsia affects between 2% and 5% of pregnancies and is one of the leading causes of perinatal morbidity and mortality worldwide. Despite strong evidence that the combination of systematic preeclampsia screening based on the Fetal Medicine Foundation preeclampsia risk calculation algorithm with treatment of high-risk patients with low-dose aspirin reduces the incidence of preterm preeclampsia more than currently used risk-factor-based screening, real-world implementation studies have not yet been done in Canada. This study aimed to assess the operational feasibility of implementing first-trimester screening and prevention of preterm preeclampsia (<37 weeks) alongside a publicly funded first-trimester combined screening program for aneuploidies. This was a prospective implementation study. Consecutive pregnant patients referred for first-trimester combined screening (11-13+6 weeks) were offered screening for preeclampsia based on the Fetal Medicine Foundation algorithm concomitantly with their aneuploidy screen. Consenting participants were screened using maternal risk factors, mean arterial pressure, uterine artery Doppler pulsatility index, pregnancy-associated plasma protein-A, and placental growth factor. Risk for preterm preeclampsia (<37 weeks) was calculated using the Fetal Medicine Foundation algorithm, and individuals with a risk score ≥1 per 100 were recommended to use aspirin (162 mg once daily at bedtime, <16-36 weeks). Implementation metrics assessed included: acceptability, operational impact, proportion of aspirin initiation, quality and safety measures, and screen performance. Between December 1, 2020 and April 23, 2021, 1124 patients consented to preeclampsia screening (98.3% uptake), and 92 (8.2%) screened positive. Appointments for patients receiving first-trimester combined screening aneuploidy and preeclampsia screening averaged 6 minutes longer than first-trimester combined screening alone, and adding uterine artery Doppler pulsatility index averaged 2 minutes. Of the 92 patients who screened as high-risk for preeclampsia, 72 (78.3%) were successfully contacted before 16 weeks' gestation. Of these, 62 (86.1%) initiated aspirin, and 10 (13.9%) did not. Performance audit identified a consistent negative bias with mean arterial pressure measurements (median multiple of the median <1 in 10%); other variables were satisfactory. There were 7 cases of preterm preeclampsia (0.69%): 5 and 2 in the high- and low-risk groups, respectively. Screening detected 5 of 7 (71.4 %) preterm preeclampsia cases, with improved performance after adjustment for aspirin treatment effect. This study confirms the operational feasibility of implementing an evidence-based preeclampsia screening and prevention program in a publicly funded Canadian setting. This will facilitate implementation into clinical service and the scaling up of this program at a regional and provincial level.

Evolving Pattern Improves the IMWG 2/20/20 Classification for Patients with Smoldering Multiple Myeloma

Introduction: Smoldering multiple myeloma (SMM) is a monoclonal gammopathy defined by the presence of an M-protein in serum ≥30 g/L and/or ≥500 mg/24h in urine and/or ≥10% of plasma cells in bone marrow, in the absence of CRAB symptoms or very high-risk criteria (SLiM). Multiple scales are available to stratify the risk of SMM progression. In clinical practice, the most used are the PETHEMA model and the 2/20/20 model established by the Mayo Clinic and validated by the International Myeloma Working Group (IMWG). These scales, in addition to providing prognostic information, allow us to guide patient follow-up and could support the start of treatment in high-risk patients. On the other hand, SMM can develop an evolving pattern, characterized by a progressive increase of the M-protein that is associated with a higher risk of progression to symptomatic multiple myeloma (MM). The objective of this study is to explore whether the incorporation of the evolving pattern to the IMWG score allows for a more accurate identification, particularly of high-risk patients. Materials and methods: Clinical records of patients diagnosed with SMM between 2011 and 2020 in a single hospital center, excluding those who met SLiM criteria, were reviewed. Progression to symptomatic MM was established according to the IMWG criteria. The evolving pattern was defined as the progressive increase of at least 10% or 25% in the M-protein size within the first 12 months from diagnosis when baseline M-protein was ≥30 g/L or <30 g/L, respectively (Ravi et al, Blood Cancer J 2016, Fernandez de Larrea et al, Leukemia 2018). The evolving type was analyzed as a time-dependent covariate. Results: Ninety three patients were initially included in the study; however, 10 patients were finally excluded: 9 for presenting SLiM criteria (1 with >60% bone marrow plasma cells, 9 with a free light chain ratio >100) and 1 for missing data. Median follow-up was 3.2 years (IQR 2-5) with a rate of progression (RP) at 2 and 4 years of 20% (95%CI 12-30) and 33.7% (95%CI 23-46), respectively. Using IMWG risk stratification model, the 2-year RP was 3.3% (95%CI 0.5-21) in low-risk patients, 9.3% (95%CI 2-32) in intermediate-risk patients, and 54 % (95%CI 35-75) in high-risk patients. Regarding the evolving pattern, it was recognized in 25% of patients. Median time from SMM diagnosis and recognition of evolving type was 9 months (IQR 6-12). The RP at 2 and 4 years was 48% (95%CI 29-71) and 65% (95%CI 44-85) for evolving type. After adding the evolving classification to IMWG model, we created a new prognostic classification system that divides patients into three risk groups: low (IMWG low or intermediate risk and non-evolving pattern), intermediate (IMWG low or intermediate risk and evolving pattern, or high risk and non-evolving pattern) and high (IMWG high risk and evolving pattern), with a 2-year RP of 2.4% (95%CI 0.3-15), 20% (95%CI 9-43) and 88.9% (95%CI 61-99), respectively. The cumulative incidence of progression to MM for the three risk groups using the IMWG and the new Evolving-2/20/20 system is represented in Figure 1A, whereas in Figure 1B the reclassification of patients with the new Evolving-2/20/20 system is shown. Regarding the validation of this score, the area under the curve (AUC) of the new score was greater than that of the IMWG and that of the evolving score independently (2y-AUC PETHEMA 0.65, IMWG 0.83, Evolving 0.77, Evolving-2/20/20 0.89; P=0.02). In addition, concordance was superior with the new score Evolving-2/20/20 (C-index 0.93) compared with PETHEMA (0.73), IMWG (0.86) and evolving (0.85) by themselves. The specificity and the positive predictive value for detecting high-risk patients at 2 years with the new model was very high (98% and 88%, respectively) compared to the other risk stratification models (PETHEMA 59% and 27%; IMWG 83 and 52%; Evolving 83% and 49%, respectively). Decision curve analysis indicated that the score was clinically useful. Conclusions: The dynamic addition of the evolving pattern to the IMWG classification (Evolving-2/20/20 system) in patients with SMM, allows more precise risk stratification and the detection of those with very high risk of progression. These patients could benefit from more intensive follow-up and may be eligible for early treatment strategies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

An Emerging Prognosis Prediction Model for Multiple Myeloma: Hypoxia-Immune Related Microenvironmental Gene Signature

Background: Multiple myeloma (MM) is a hematologic malignancy characterized by clonal proliferation of malignant plasma cells. Hypoxia and the immune microenvironment play vital roles in the carcinogenicity and evolution of MM. In this study, we attempted to construct a microenvironmental gene marker associated with hypoxia immunity for effective prognostic prediction and risk stratification. Methods: MM-related datasets (GSE136324, GSE47552 and GSE136337) were downloaded from Gene Expression Omnibus (GEO). A Kaplan-Meier (K-M) survival curve was applied to excavate survival differences among different hypoxia clusters, and the hypoxia state was divided into high hypoxia and low hypoxia groups according to the prognosis. The expression data algorithm was used to estimate the immune score of each MM patient. Based on the optimal truncation immune score value, MM patients were divided into high and low immune score subgroups. The R packages were applied to identify the risk differentially expressed genes (DEGs) and protective DEGs. Univariate Cox and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses were applied to identify prognosis-related genes. Receiver Operating Characteristic curves and K-M survival curves were applied to verify the validity and agility of the prognostic signature. The cell type identification by estimating relative subsets of RNA transcripts algorithm was applied to analyze immune cell infiltration. Quantitative real-time PCR was used to test the signature in vitro. Cell proliferation was measured by a CCK-8 assay. The levels of apoptotic rate were analyzed by the flow cytometer. Cell migration and invasion ability were estimated by Transwell membranes and Matrigel. NOD/SCID mice were divided into four groups: normoxia control (CTL), normoxia shDDIT4 (CTL+shDDIT4), intermittent hypoxia control (IH), and IH shDDIT4 (IH+shDDIT4). CTL had an oxygen concentration of 21% while IH had a nadir of 6%~8%. Results: A total of 867 MM samples were classified according to hypoxia status and immune score and were classified into Hypoxia.low/Immune.high, Hypoxia.high/Immune, lowand mixed groups. K-M survival analysis showed patients in the Hypoxia.low/Immune.high group had a better prognosis than others. Overlapping the three groups of risk DEGs and protective DEGs. There were 472 protective DEGs and 205 risk DEGs with supporting evidence from hypoxia, immune and combing hypoxia/ immune groups. In GSE47522, 2633 DEGs were screened between normal and MM. 81 key hypoxia-immune-related genes were overlapped by the Venn diagram between MM and normal DEGs, protective DEGs and risk DEGs. Using GSE136324 as a training cohort, a univariate Cox regression analysis was performed on 81 key genes. We identified 44 hypoxia-immune-related prognostic DEGs statistically related to the overall survival time of MM patients. Then, an 8-gene signature (including CHRDL1, DDIT4, DNTT, FAM133A, MYB, PRR15, QTRT1, and ZNF275) was identified using the LASSO regression algorithm. MM patients were divided into high-risk and low-risk groups based on a threshold of the median risk score in the prognostic value of the 8-gene signature. K-M curves suggested that the MM patients in the low-risk group showed a statistically longer overall survival than those in the high-risk group. The AUC of 1 year in the training cohort was greater than 0.7. Univariate and multivariate Cox regression analyses showed that the risk score could be an independent prognostic risk factor. Moreover, we revealed that the proportions of 17 types of immune cells were significantly different between the two risk groups, . In the high-risk group, PD-L1 expression levels were higher than in the low-risk group. Finally, we found knockout of DDIT4 inhibited tumor formation in vitro under hypoxia. Further, the survival rate of the IH+shDDIT4 group was higher than that of the IH group. Moreover, both tumor volume and tumor weight in the IH+shDDIT4 group were reduced. Conclusions: We established a hypoxia-immune related prognostic signature. It could predict the prognosis of MM well and was related to the tumor microenvironment of MM. The downregulation of DDIT4 inhibited tumor formation and development in vitro and vivo under hypoxia. Meanwhile, our results suggest that the immune checkpoint inhibitors, PD-L1 inhibitors, may be helpful in the treatment of high-risk patients.

Abstract 13958: Evolocumab Alters Vascular Function in Patients With Cardiovascular Disease

Background: The aim of this study was to analyze the effect of evolocumab on vascular function and structure in patients with cardiovascular disease. Methods: This was a prospective, double-blinded, randomized, controlled study (NCT03626831) including patients with cardiovascular disease and treated with statins. Patients were consecutively randomized (1:1) to either evolocumab treatment (420mg was administrated twice during the study) or placebo. All patients underwent vascular examination at baseline, and after 1, 4 and 8 weeks of treatment by the SphygmoCor XCEL System (pulse wave analysis) and the UNEX EF 18G system (endothelial function). Endothelial function parameter such as flow-mediated vasodilation (FMD), low flow-mediated vasoconstriction (L-FMC) and vasoactive range (VAR) were measured. Moreover, pulse wave analysis parameters such as central systolic pressure, central pulse pressure, augmentation index, pulse wave velocity were measured. Results: 103 patients with a mean age of 66.2 (±7.7) years and a mean LDL-cholesterol of 98.2 (±19.1) mg/dl completed the study. LDL-cholesterol decreased significantly already after 1 week of treatment with evolocumab compared to baseline (-47.4 (±13.1) mg/dl). Endothelial function parameter (VAR) increased after 8 weeks of treatment with evolocumab compared to baseline (p=0.034), whereas there was no significant change at 1 and 4 weeks after treatment. Moreover, an improvement in VAR from baseline at week 8 was found with evolocumab compared to placebo (p=0.045). No change in the pulse wave analysis parameters were found with treatment. In a subgroup analysis, in patients with age ≤67 years, lower systolic blood pressure (≤125 mmHg) or higher baseline LDL-cholesterol (&gt;95 mg/dl), significant evolocumab treatment effect was found in VAR improvement (p=0.006, p=0.049 and p=0.042, respectively) from baseline at week 8. Conclusion: Our data indicate that endothelial function could be improved with evolocumab treatment in high-risk patients with preexisting cardiovascular disease and on statin therapy. Our results contribute to the mechanistic explanation why lower incidence of the cardiovascular composite endpoint has been demonstrated in the FOURIER study.

Mid to Long-Term Echocardiographic Follow-up of Patients Undergoing Transcatheter Tricuspid Valve-in-Valve Replacement for Degenerated Bioprosthetic Valves: First Single-Center Report from Iran.

Transcatheter tricuspid valve-in-valve (TTViV) replacement has become an alternative treatment in high-risk patients with bioprosthetic valve degeneration. This is the first report on the mid to long-term echocardiographic findings of patients who underwent TTViV replacement in a cardiac referral center in Iran. Data of 12 patients, consisting of 11 women and 1 man, who underwent TTViV replacement between 2015 and 2021 were reviewed retrospectively. The patients underwent echocardiography before the procedure and at a mean follow-up time of 3.17±1.75 years. All the patients had New York Heart Association (NYHA) function class III/IV before TTViV. Six patients had tricuspid regurgitation, 1 had tricuspid stenosis, and 5 had both. All the patients had successful TTViV. The mean time from the initial valve surgery to TTViV was 6.25±2.45 years. At follow-up, 2 patients had died: 1 due to COVID-19 pneumonia and 1 without a known cause. The remaining 10 patients experienced improvements in the NYHA functional class. Echocardiographic measures showed significant improvements. Transvalvular mean gradient pressure decreased from 7.08±1.98 mm Hg to 5.29±1.63 mm Hg (P=0.028), tricuspid valve pressure half time decreased from 245.00±49.46 ms to 158.64±57.41 ms (P=0.011), tricuspid regurgitation gradient decreased from 39.91±7.31 mm Hg to 26.72±8.99 mm Hg, and left ventricular ejection fraction increased from 47.71±4.70% to 49.79±4.58% (P=0.046). There was no significant paravalvular or transvalvular leakage at follow-up. This is a single-center report on the mid and long-term echocardiographic follow-up of patients after TTViV replacement. Our study showed that TTViV was a safe and efficient method in treating high-risk patients with degenerated bioprosthetic tricuspid valves and had favorable echocardiographic and clinical results.

PCSK-9-inhibitor therapy improves endothelial function in high-risk patients with cardiovascular disease

Abstract Background Impaired endothelial function predicts cardiovascular events. The aim of this study was to analyse the effect of evolocumab on endothelial function in patients with cardiovascular disease and on obligatory statin therapy. Methods This was a prospective, double-blinded, randomized, controlled, single center study including patients with cardiovascular disease (diagnosis of coronary artery disease, non-hemorrhagic stroke, transient ischemic attack or symptomatic peripheral artery disease) and treated with statins, similar to the inclusion criteria of the FOURIER study. Patients were consecutively randomized (1:1) to either evolocumab treatment (420mg was administrated in monthly intervals, twice during the study) or placebo. All patients underwent examination of endothelial function at baseline, and after 1, 4 and 8 weeks of treatment by a semi-automatic high-resolution ultrasound system (UNEX EF 18G; Unex Co., Nagoya, Japan). Endothelial function parameter such as flow-mediated vasodilation (FMD; vasodilator responsiveness), low flow-mediated vasocontriction (L-FMC; vasoconstrictor responsiveness) and vasoactive range (VAR; total vasomotor responsiveness) were measured. Results 103 patients with a mean age of 66.2 (±7.7) years and a mean LDL-cholesterol of 98.2 (±19.1) mg/dl completed the study. 83.5% of the study population was known to have coronary artery disease. Endothelial function parameter (VAR) increased after 8 weeks of treatment with evolocumab compared to baseline (p=0.034), whereas there was no significant change at 1 and 4 weeks after treatment. Moreover, an improvement in VAR from baseline at week 8 was found with evolocumab compared to placebo (p=0.045). In a subgroup analysis, in patients with age ≤67 years, lower systolic blood pressure (≤125 mmHg) or higher baseline LDL-cholesterol (&amp;gt;95 mg/dl), significant evolocumab treatment effect was found in VAR improvement (p=0.006, p=0.049 and p=0.042, respectively) from baseline at week 8. No serious adverse event related to study medication occurred during the study. Conclusion Our data indicate that endothelial function could be improved with evolocumab treatment in high-risk patients with preexisting cardiovascular disease and on statin therapy. Our results contribute to the mechanistic explanation why lower incidence of the cardiovascular composite endpoint has been demonstrated in the FOURIER study. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): AMGEN GmbH

Oral fluoroquinolones and risk of aortic dissection and aortic aneurysm: a nationwide nested case-control study

Abstract Background Oral fluoroquinolones are commonly prescribed antibiotics. Observational studies have shown an association between fluoroquinolone-use and subsequent risk of aortic aneurysm (AA) and aortic dissection (AD) due to a potential collagen degrading effect of fluoroquinolones. Purpose To investigate if fluoroquinolone-use was associated with increased rates of AA or AD in patients without known aortic disease. Secondly, to investigate if fluoroquinolone-use was associated with increased all-cause mortality and aortic interventions in high-risk patients with known aortic disease. Methods We used a nested case-control study design in which individuals aged 30–100 years from 2003 to 2018 were included from Danish nationwide registers. Exclusion criteria were bicuspid aortic valve, coarctation of the aorta, and connective tissue disease. A main cohort and a secondary high-risk cohort were defined. The main cohort comprised patients without history of AA/AD in which two case definitions were used: 1) A broad case definition of first-time AA/AD. 2) A severe case definition of ruptured AA/AD. The high-risk cohort comprised patients surviving index AA/AD admission in which cases were defined as all-cause mortality and aortic interventions. Cases were matched on age, sex, and year of inclusion in a 1:30 ratio with controls. For the main cohort, a potential dose-response effect was investigated using groups of cumulative defined daily doses (cDDD) of fluoroquinolones. Hazard ratios (HR) with 95% confidence intervals (CI) for fluoroquinolone-use compared with amoxicillin as an active comparator were obtained from time-dependent Cox regression models using multiple exposure windows. Results The main cohort comprised 4.81 million individuals with 43,280 cases. Short-term 30-day, intermediate-term 90-day, and long-term 1-year fluoroquinolone use were all not associated with AA/AD (30-day HR 1.18 [95% CI: 0.84 to 1.66]; 90-day HR 1.12 [95% CI 0.96 to 1.30]; 1-year HR 1.00 [95% CI 0.93 to 1.07]). Using a severe case definition of ruptured AA/AD yielded comparable results. For the dose-response analysis, increasing cDDD did not confer increased rates of AA/AD (1–5 cDDD: Reference group; 6–10 cDDD: HR 1.03 [95% CI: 0.87 to 1.23]; &amp;gt;10 cDDD: HR 1.00 [95% CI 0.83 to 1.29]) (Figure 1). The secondary high-risk cohort included 20,195 patients surviving index admission with 9,183 cases of all-cause mortality and 1,768 cases of aortic interventions. The 30-day HR for all-cause mortality was 1.21 (95% CI 0.92 to 1.60) and the 60-day HR 1.06 (95% CI 0.89 to 1.26). No association with aortic interventions was found either (Figure 2). Conclusion Fluroquinolone-use was not associated with AA/AD. Furthermore, fluoroquinolone-use was not associated with all-cause mortality or aortic interventions in potentially susceptible patients with known aortic disease. These findings do not support an increased risk of AA/AD with fluoroquinolone-use. Funding Acknowledgement Type of funding sources: None.

Comparable Outcomes for Bebtelovimab and Ritonavir-Boosted Nirmatrelvir Treatment in High-Risk Patients With Coronavirus Disease-2019 During Severe Acute Respiratory Syndrome Coronavirus 2 BA.2 Omicron Epoch.

The effectiveness of bebtelovimab in real-world settings has not been assessed. In this retrospective cohort study of 3607 high-risk patients, bebtelovimab was used more commonly than nirmatrelvir-ritonavir for treatment of coronavirus disease 2019 (COVID-19) among older patients, immunosuppressed patients, and those with multiple comorbid conditions. Despite its use in patients with multiple comorbid conditions, the rate of progression to severe disease after bebtelovimab (1.4% [95% confidence interval, 1.2%–1.7%]) was not significantly different from that for nirmatrelvir-ritonavir treatment (1.2% [.8%–1.5%]). Our findings support the emergency use authorization of bebtelovimab for treatment of COVID-19 during the Omicron epoch dominated by BA.2 and subvariants.

Hepatic encephalopathy is not a contraindication to pre-emptive TIPS in high-risk patients with cirrhosis with variceal bleeding

BackgroundA pre-emptive transjugular intrahepatic portosystemic shunt (pTIPS) reduces mortality in high-risk patients with cirrhosis (Child-Pugh C/B+active bleeding) with acute variceal bleeding (AVB). Real-life studies point out that <15% of patients...

Clinical Impact of Monoclonal Antibodies in the Treatment of High-Risk Patients with SARS-CoV-2 Breakthrough Infections: The ORCHESTRA Prospective Cohort Study.

The clinical impact of anti-spike monoclonal antibodies (mAb) in Coronavirus Disease 2019 (COVID-19) breakthrough infections is unclear. We present the results of an observational prospective cohort study assessing and comparing COVID-19 progression in high-risk outpatients receiving mAb according to primary or breakthrough infection. Clinical, serological and virological predictors associated with 28-day COVID-19-related hospitalization were identified using multivariate logistic regression and summarized with odds ratio (aOR) and 95% confidence interval (CI). A total of 847 COVID-19 outpatients were included: 414 with primary and 433 with breakthrough infection. Hospitalization was observed in 42/414 (10.1%) patients with primary and 8/433 (1.8%) patients with breakthrough infection (p < 0.001). aOR for hospitalization was significantly lower for breakthrough infection (aOR 0.12, 95%CI: 0.05–0.27, p < 0.001) and higher for immunocompromised status (aOR:2.35, 95%CI:1.08–5.08, p = 0.003), advanced age (aOR:1.06, 95%CI: 1.03–1.08, p < 0.001), and male gender (aOR:1.97, 95%CI: 1.04–3.73, p = 0.037). Among the breakthrough infection group, the median SARS-CoV-2 anti-spike IgGs was lower (p < 0.001) in immunocompromised and elderly patients >75 years compared with that in the immunocompetent patients. Our findings suggest that, among mAb patients, those with breakthrough infection have significantly lower hospitalization risk compared with patients with primary infection. Prognostic algorithms combining clinical and immune-virological characteristics are needed to ensure appropriate and up-to-date clinical protocols targeting high-risk categories.

Low triiodothyronine syndrome is associated with stroke-associated pneumonia.

Stroke-associated pneumonia (SAP) is the most common early consequence in patients suffering from an acute ischaemic stroke (AIS). The purpose of this study was to explore the possible relationship between low triiodothyronine (T3) syndrome and SAP in stroke patients. This study recruited 2460 consecutive AIS patients. SAP was defined according to the modified Centers for Disease Control and Prevention criteria for hospital-acquired pneumonia. The thyroid hormones levels were measured within 24 h after admission. Low T3 syndrome was characterized as T3 below the lower limit of the reference interval accompanied by normal TSH levels. Among the total patients, 336 (13.7%) patients were diagnosed with SAP. SAP in individuals with low T3 syndrome was substantially greater (p < .001) as compared to those without low T3 syndrome. After adjusting for possible confounders, low T3 syndrome (adjusted odds ratio [aOR]=1.59; 95% confidence interval [CI], 1.20-2.09; p=.001) remained significant in our logistic model. Patients with low T3 syndrome had a higher risk of severe SAP (aOR=2.17, 95% confidence interval [CI] 1.38-3.44; p=.001). Low T3 syndrome, independent of recognized risk factors, is a possible risk factor for in-hospital SAP, which can help clinicians in the early detection and treatment of high-risk patients.

Predictors of pneumonia in patients with acute spontaneous intracerebral hemorrhage in Algarve, Southern Portugal

IntroductionFollowing the hyperacute phase of spontaneous intracerebral hemorrhage (SICH), the severest form of stroke, pneumonia emerges as the leading cause of morbidity and mortality. Prevention of stroke associated pneumonia (SAP) is fundamental to improve the prognosis of SICH patients. AimIdentify clinical, sociodemographic and process of care factors associated with occurrence of SAP after SICH in Algarve, southern Portugal. MethodsObservational, retrospective study of community representative consecutive case series of patients with SICH admitted to the sole public hospital in the region. Logistic regression was used to identify predictors of SAP after SICH. ResultsA total of 525 patients were included. The mean age was 71 ( ± 13) years and 64% were men. SAP occurred in 165 (31.5%). Lower Glasgow Coma Scale score (GCS score): ≤ 8 (OR= 2.087; 95% CI= [1.027;4.424]; p = 0.042) and GCS 9–12 (OR= 1.775; 95% CI= [1.030;3.059]; p = 0.039); prolonged emergency room stay (OR= 8.066; 95%CI=[3.082;21.113]; p < 0.001) and hyperactive delirium (OR=2.860; 95% CI= [1.661;4.925]; p < 0.001) increased the likelihood of SAP. Being younger, ≤ 59 years (OR= 0.391; 95% CI= [0.168; 0.911]; p = 0.029) and 60–71 years (OR= 0.389; 95% CI= [0.185; 0.818]; p = 0.013); and having less severe SICH/intracerebral hemorrhage score (ICH score) ≤ 2 (OR=0.601; 95% CI= [0.370; 0.975]; p = 0.039), decreased the risk of SAP. ConclusionAfter SICH, SAP occurs in approximately a third of patients. Non preventable (admission severity, ageing) and potentially preventable (prolonged emergency room stay, hyperactive delirium) determine the occurrence of SAP. Intensification of preventive intervention in high-risk patients, delirium prevention and improvement of the process of care can potentially reduce the occurrence of SAP after SICH.

Proteomic analysis of cardiometabolic biomarkers and predictive modeling of severe outcomes in patients hospitalized with COVID-19

BackgroundThe high heterogeneity in the symptoms and severity of COVID-19 makes it challenging to identify high-risk patients early in the disease. Cardiometabolic comorbidities have shown strong associations with COVID-19 severity in epidemiologic studies. Cardiometabolic protein biomarkers, therefore, may provide predictive insight regarding which patients are most susceptible to severe illness from COVID-19.MethodsIn plasma samples collected from 343 patients hospitalized with COVID-19 during the first wave of the pandemic, we measured 92 circulating protein biomarkers previously implicated in cardiometabolic disease. We performed proteomic analysis and developed predictive models for severe outcomes. We then used these models to predict the outcomes of out-of-sample patients hospitalized with COVID-19 later in the surge (N = 194).ResultsWe identified a set of seven protein biomarkers predictive of admission to the intensive care unit and/or death (ICU/death) within 28 days of presentation to care. Two of the biomarkers, ADAMTS13 and VEGFD, were associated with a lower risk of ICU/death. The remaining biomarkers, ACE2, IL-1RA, IL6, KIM1, and CTSL1, were associated with higher risk. When used to predict the outcomes of the future, out-of-sample patients, the predictive models built with these protein biomarkers outperformed all models built from standard clinical data, including known COVID-19 risk factors.ConclusionsThese findings suggest that proteomic profiling can inform the early clinical impression of a patient’s likelihood of developing severe COVID-19 outcomes and, ultimately, accelerate the recognition and treatment of high-risk patients.

Transesophageal Echocardiography (TEE)-Guided Paravalvular Leak (PVL) Closure: Expanding Horizons Beyond Operating Room

AbstractParavalvular leak (PVL) is a common, yet challenging entity occurring due to dehiscence of the annular tissue around the prosthetic valve, resulting in regurgitation of blood retrogradely. Although any prosthetic valve can be subjected to the risk of developing PVL, it is most commonly reported with the mitral valve followed by the aortic valve. The incidence of mitral PVL is around 7 to 17%, whereas with the aortic valve it is 5 to 10%. Symptomology can vary from asymptomatic patients with mild PVL to disabling symptoms pertaining to heart failure and hemolysis. TEE plays a pivotal role in the overall assessment along with procedural guidance for their closure. Multiple two-dimensional (2D) imaging views are required to scan the entire sewing ring diameter of a prosthetic valve. Three-dimensional (3D) TEE can give crucial information such as the number, size, shape, and circumference of the defects. 3D mitral en face view can give anatomical localization of the defect. During the procedure, TEE can assist in the confirmation of the position of the guidewire through the defect and not through the prosthetic valve. It also helps to conform to the adequate positioning of the vascular plug device and unrestrictive movement of the native prosthetic heart valve. TEE when combined with fluoroscopy can help in real-time guidance of passage of the guidewire and transcatheter device in relation to the prosthetic valve. Recently, Ahmed et al have named this technology as “Fusion Technique,” where they have combined real-time 2D and 3D TEE with fluoroscopy to facilitate the closure of PVL. Now that the time of minimally invasive surgery has taken over conventional surgery and fast tracking and enhanced recovery after surgery (ERAS) is the need of the moment, percutaneous PVL closure is preferred over surgical PVL closure. A study done by Gakrinho et al showed that percutaneous PVL closure has a reasonable success rate along with a low complication rate and the results are comparable to surgical treatment in high-risk patients. We hereby share our experience of the successful closure of PVL via the transcatheter technique using various 2D and 3D techniques.

Clinical Characteristics and Prognostic Factors of Severity in Covid-19 Patients in Lahore, Pakistan

Background: The coronavirus disease outbreak of 2019 (COVID-19) has developed into a global emergency. COVID-19's severity is strongly correlated with its mortality rate. We aimed to examine the demographic, medical, laboratory, and imaging characteristics of 120 patients affected by COVID-19. Methods: 120 COVID-19 infected- patients who tested positive from the throat swab specimen on quantitative reverse transcriptase-polymerase chain reaction (q RT-PCR) were included. Demographic, clinical, radiographic, and laboratory data were obtained and analyzed. Results: Male gender, urban residence, current smoker, exposure history, sore-throat, dyspnoea, cough, headache, diarrhea, coronary heart disease, chronic obstructive lung disease, and cancer, decreased level of hemoglobin and albumin and increased level of lymphocyte count, leukocyte count, LDH level, D-dimer, serum ferritin, total bilirubin, urea level (p-value &lt; 0.05) were contributing factors towards disease severity. In the binary logistic regression model LDH (OR 1.002, [CI, 1.001-1.003]; p = 0.001), and D-dimer (OR 1.377, [CI, 1.161-1.633]; p=0.001) were independent predictors of disease severity. Conclusion: Appropriate evaluation of prognostic factors and provision of the appropriate interventions in high-risk patients can decrease the mortality associated with COVID-19