Disease In High-risk Patients Research Articles

The EFLM European Urinalysis Guideline 2023.

The EFLM Task and Finish Group Urinalysis has updated the ECLM European Urinalysis Guidelines (2000) on urinalysis and urine bacterial culture, to improve accuracy of these examinations in European clinical laboratories, and to support diagnostic industry to develop new technologies. Graded recommendations were built in the following areas. Strategies of urine testing are described to patients with complicated or uncomplicated urinary tract infection (UTI), and high or low-risk to kidney disease. Patient preparation, and urine collection are supported with two quality indicators: contamination rate (cultures), and density of urine (chemistry, particles). Measurements of both urine albumin and α1-microglobulin are recommended for sensitive detection of kidney disease in high-risk patients. Performance specifications are given for urine protein measurements and quality control of multiproperty strip tests. Procedures for microscopy are reviewed for diagnostic urine particles, including urine bacteria. Technologies in automated particle counting and visual microscopy are updated with advice how to verify new instruments with the reference microscopy. Chromogenic agar is recommended as primary medium in urine cultures. Limits of significant growth are reviewed, with an optimised workflow for routine specimens, using leukocyturia to reduce less important antimicrobial susceptibility testing. Automation in bacteriology is encouraged to shorten turn-around times. Matrix assisted laser desorption ionization time-of-flight mass spectrometry is applicable for rapid identification of uropathogens. Aerococcus urinae, A. sanguinicola and Actinotignum schaalii are taken into the list of uropathogens. A reference examination procedure was developed for urine bacterial cultures.

PP2A activation as a new therapeutic strategy in neuroblastoma: Making sense out of senescence.

10055 Background: Neuroblastoma (NBL) is the most common extracranial solid tumor in children, accounting for 15% of all pediatric cancer deaths. The five-year survival rate for children with high-risk disease is less than 50%, with the primary reasons for mortality being refractory and relapsed disease. One hypothesis for the poor response to therapy and propensity for recurrent disease in high-risk patients is treatment-induced senescence (TIS). Protein phosphatase 2A (PP2A) is a known tumor suppressor that is downregulated in NBL. PP2A activation has been shown to reverse cellular senescence in non-cancerous pathologies, therefore we hypothesized that reactivation of PP2A using novel small molecule activators would function as a novel senotherapeutic in NBL. Methods: We employed MYCNamplified, SK-N-BE(2), and non-amplified, SK-N-AS, established human NBL cell lines. Topotecan, a common NBL chemotherapeutic, known to induce senescence, and ATUX-1215, a small molecule PP2A activator, were utilized. NBL cells were treated with topotecan and ATUX-1215 alone, as well as in combination. Colorimetric assays detected cell viability and proliferation. Immunoblotting identified proteins of interest including γ-H2AX and CCL2. TIS was detected by S-β galactosidase (Sβgal) assay. Results: We found increased expression of the senescence marker, histone γ-H2AX, and increased Sβgal-positive tumor cells supporting the ability of topotecan to generate TIS in NBL. Following treatment with PP2A activator in combination with topotecan, markers of TIS are decreased in both MYCN amplified and non-amplified NBL cells. Further, and importantly, PP2A activation reversed the effects of topotecan TIS and acted in a synergistic fashion to decrease NBL cell viability. Conclusions: Activation of PP2A with a novel small molecule ameliorates topotecan-induced TIS in NBL cells irrespective of MYCN status. These results are promising, providing a potential novel therapeutic adjunct to children who are most in need of innovative interventions.

Community pharmacist-led point-of-care eGFR screening: early detection of chronic kidney disease in high-risk patients

Adherence to scheduled physician screenings for renal function monitoring in patients with chronic kidney disease (CKD) or those at high risk remains suboptimal despite the endorsement of regular screenings by several clinical practice guidelines. Our study aims to assess the effectiveness of a point-of-care CKD screening program led by these pharmacists using the PICCOLO device while recognizing the unique position of community pharmacists in primary care. We conducted an 11-month prospective point-of-care interventional research study in the United Arab Emirates to evaluate the performance of a community pharmacist-led CKD screening program for high-risk patients. Six diverse community pharmacies were selected based on staff availability, patient volume, and their offered range of services. Eligible individuals with risk factors for CKD were identified during medication evaluations. The PICCOLO Comprehensive Metabolic Panel facilitated on-site blood analysis, delivering estimated Glomerular Filtration Rate (eGFR) results within 10 to 15 min. Data also included eGFR categories, demographic information, and insights into lifestyle and health habits collected through a questionnaire. Pharmacists conducted comprehensive medication reviews and offered referrals and lifestyle guidance as part of the program. The study encompassed a total of 400 patients, with an average age of 69 ± 13.4 years within the study cohort. Notably, 38.8% (155 individuals) of the 400 patients were found to have undiagnosed CKD stages 3–5. Univariate logistic regression analysis revealed a significant association between a higher incidence of CKD stages 3–5 and factors such as older age, a history of hypertension, vascular disease, and diabetes mellitus. In the multivariate regression model, age and a history of diabetes mellitus emerged as significant predictors of an elevated risk of CKD. This study sheds light on the viability and impact of CKD screening programs conducted by community pharmacists, particularly in detecting CKD stages 3–5. The findings have implications for healthcare policies, as they can influence the enhancement of early detection and management of CKD. Moreover, these insights may catalyze focused screening initiatives and strengthen collaboration between community pharmacies and healthcare systems to benefit patients at high risk of CKD.

Surveillance over cytomegalovirus (CMV) reactivation following hematopoietic stem cell transplantation: a single-center experience

Cytomegalovirus (CMV) infection is widespread and usually asymptomatic in immunocompetent individuals. However, during immune suppression, especially after hematopoietic stem cell transplantation (HSCT), viral reactivation may result in symptomatic infection and end-organ disease. Because there is high incidence of CMV seropositivity in Bulgaria, CMV infection/reactivation is an expected common complication in HSCT recipients which requires frequent monitoring. CMV reactivation monitoring via qRT PCR has a significant role in terms of the moment of initiating pre-emptive therapy in these high-risk patients in order to avoid the development of CMV disease and better clinical management. The aim of this study was to determine and analyze the incidence of CMV reactivation in HSCT recipients in a new transplant center in Bulgaria. The incidence of early CMV reactivation after HSCT in our center is very high (76.7%) most likely related to the high-risk donor/recipient (D/R) profile of our recipients. The mean period from HSCT to the first positive PCR result was quite short, 21.5 days on average. The highest-risk group donor-/recipient+ (D-/R+) experienced the longest and the highest levels of viremia, as well as the highest number of reactivations. The nature of the D/R status most significantly affected the degree of viral load. Our data demonstrate the essential role of monitoring of CMV with reliable and sensitive laboratory methods, such as qRT-PCR to avoid development of CMV disease in high-risk patients.

Herbal Components for the Treatment of Various Kidney Disorders

Abstract:: Acute kidney injury is described as a loss of renal excretory function that occurs suddenly. AKI is one of several ailments grouped together as acute kidney diseases and disorders (AKD), in which progressive degradation of kidney function or persistent renal dysfunction is associated with irreversible loss of kidney cells and nephrons, potentially leading to chronic kidney disease (CKD). The prevalence and incidence of KDs are assessed in light of population disparities in the prevalence of risk factors such as diabetes, hypertension, and obesity. However, the presence of these associated illnesses does not fully explain the increased rate of progression of chronic renal disease in high-risk patients (CKD). The development of renal disease is accompanied by a decline in renal function, which eventually leads to renal failure. The current status of diagnostic testing does not allow for accurate early disease diagnosis, prognosis, or therapy efficacy monitoring. Despite significant advances in care and understanding of the causes of acute renal failure (ARF), many aspects of ARF remain controversial, confusing, and uncertain. Accurate information on the disease's prevalence, genesis, and clinical manifestations is required to successfully advocate for enough funding and resources to manage the disease. Herbal components for the treatment of a variety of kidney disorders, and the page includes a list of plants that are good for kidney treatment. This review focuses on several herbal products used to treat renal problems. It is clear from this study that medicinal plants play an important role in the fight against many different diseases. Several different plants and plant extracts have been shown to have beneficial effects in treating renal disease. These medications have great promise for use in treating kidney damage because of their nephroprotective, cytoprotective, immunomodulatory, antioxidant, anti-inflammatory, and reducing effects on oxidative stress, renal hypertension, and blood toxins such as urea, creatinine, and others. Therefore, India's traditional medicine offers a wide variety of medications that can be utilized in renal illnesses due to their effectiveness in both treating the ailment and restoring normal kidney function. Therefore, it is suggested that additional research be conducted to learn many aspects and mechanisms of medications.

Surveillance for COVID-19 associated mucormycosis: A coordinated effort in prevention and management of rhino-orbital mucormycosis

Abstract Context: Patients of coronavirus disease 2019 (COVID-19) and factors inducing a diabetogenic state are at increased risk for rhino-orbital mucormycosis (ROM). Efforts to diagnose ROM in its pre-clinical stage would avoid the disease and its consequences. Aim: This study aimed to diagnose ROM in the pre-clinical stage of the disease in high-risk patients and treat patients accordingly. Settings and Design: This is a single-center, prospective study conducted at a tertiary care center in Northern India in collaboration with departments of Otolaryngology, Internal Medicine, and Mycology. Materials and Methods: Fifty-three high-risk patients were enrolled in the study, and all underwent bedside nasal endoscopy with tissue sampling for fungal culture. Patients with suspicious nasal endoscopy findings but negative fungal culture were prescribed oral posaconazole. Those with positive fungal hyphae on nasal endoscopy and culture underwent surgical intervention followed by intravenous amphotericin B, while the remaining patients were kept on follow-up. Statistical Analysis Used: Statistical analysis was performed using the Statistical Package for Social Sciences software. Results: Among the 53 patients, 13 (24.5%) patients had abnormalities on nasal endoscopy, while the remaining 40 (75.5%) patients had normal nasal mucosal cavities. Seven patients (13.2%) underwent surgery and received intravenous liposomal amphotericin B, while another 7 (13.2%) received oral posaconazole. Thirty-five (66.03%) patients were placed under observation, and 4 (7.5%) patients died due to COVID-19-related illness. Conclusions: Nasal endoscopic-guided tissue sampling for fungal culture serves as a valuable surveillance tool for predicting ROM in COVID-19 patients.

Sclerobanding in the treatment of second and third degree hemorrhoidal disease in high risk patients on antiplatelet/anticoagulant therapy without suspension: a pilot study.

Around 20% of population in western countries is under anticoagulant treatment. However, there is paucity of evidence about the treatment of HD in patients under anticoagulant/antiplatelet therapy, although both suspension and continuation in the perioperative period may increase the risk of severe complications. The aim of this pilot study was to confirm the feasibility and safety of sclerobanding (Combined Rubber Band Ligation with 3% Polidocanol Foam Sclerotherapy), an office-based procedure, for the treatment of second-and third-degree HD in patients under anticoagulant/antiplatelet therapy without suspension. Patients affected by second-third-degree haemorrhoids unresponsive to conservative treatment and under anticoagulant/antiplatelet were enrolled between November 2019 and October 2021. Postoperative complications, readmission, mortality and reintervention during the follow-up were evaluated. Fifty-one patients were recruited, 23 female (45.1%) and 28 male (54.9%), with an average age of 65 years ± 11.4 SD (range 42-90). Twenty-seven patients (52.9%) had II-degree haemorrhoidal disease, and 24 (47.1%) had grade III-degree. The most frequently taken medications were dual antiplatelet therapy (51%) and new oral anticoagulants (NOACs) (21.6%). The mean follow-up was 23 months. No intraoperative complications were recorded. The rate of complications in the first postoperative month was 13.7%, represented by mild complications: 6 cases of moderate to severe pain and 1 case (2%) of thrombosis of a residual haemorrhoidal nodule, all regressing after conservative therapy. No severe complications were reported. Postoperative complications were not statistically significantly associated with the number of nodules treated (1, 2, or 3), the disease grade (2nd vs. 3rd) or the specific anticoagulant/antiplatelet regimen. During follow-up, 2 patients (4%) required a new procedure for recurrent bleeding: one an infrared photocoagulation as outpatient, and another a haemorrhoidectomy after 3 months. No cases of intraoperative or postoperative mortality occurred. Sclerobanding is a safe and effective technique in treating intermediate-grade haemorrhoidal disease in patients at high risk on anticoagulant/antiplatelet therapy. Sclerobanding is repeatable, usually does not require anaesthesia, and is cost-effective. Observational multicentre studies with a larger number of patients and controlled clinical trials will be needed to confirm these results.

Moderate-high intensity exercise associates with reduced incident alcohol-associated liver disease in high-risk patients.

Therapies to prevent alcohol-associated liver disease (ALD) in high-risk patients are needed. In this retrospective association study, we examined whether patients with alcohol use disorder (AUD) who reported greater exercise were less likely to develop liver disease. In this retrospective cohort study, we used the Mass General Brigham Biobank to investigate the impact of both moderate-high and light-intensity exercise on the development of ALD in patients with AUD, using clinician-provided diagnostic International Classification of Diseases 10 codes. Exercise was evaluated using a questionnaire completed after an AUD diagnosis, and before evidence of liver disease. Cox regressions were used to generate hazard ratios (HRs) for the development of ALD. 1987 patients met inclusion criteria. These patients were followed for an average of 10.7years. In multivariable analyses, we found that patients that reported at least 2.5h of moderate-high intensity exercise/week (confidence interval recommendation for exercise) were less likely to develop ALD compared to patients that did not exercise (HR: 0.26, 95%CI: 0.085-0.64, P = 0.007). Indeed, each hour of moderate-high intensity exercise was associated with progressively decreasing odds of developing ALD (HR: 0.76, 95%CI: 0.58-0.91, P = 0.02). Conversely, patients who did not engage in any moderate-high intensity exercise were more likely to develop ALD (HR: 2.76, 95%CI: 1.44-5.40, P = 0.003). In our cohort, patients with AUD who reported moderate-high intensity exercise showed a lower association with incidence of ALD development than patients who did not exercise.

Clinical outcome of Mantle Cell Lymphoma patients with high-risk disease (high-risk MIPI-c or high p53 expression)

Currently, treatment allocation of patients with Mantle Cell Lymphoma (MCL) is mainly based on age and medical fitness. The combined MCL International Prognostic Index (MIPI-c) allows to predict prognosis using clinical factors (MIPI) and the Ki-67 index. However, high p53 expression as surrogate for TP53 alterations has demonstrated to be an independent predictor for poor outcome. We aimed to define a clear high-risk group based on the combination of MIPI, Ki-67 and p53 expression/TP53 alteration. A total of 684 patients from the prospective European MCL-Younger and MCL-Elderly trials were evaluable. The classification of high-risk disease (HRD) as high-risk MIPI-c or p53 expression >50% versus low-risk disease (LRD) as low, low-intermediate or high-intermediate MIPI-c and p53 expression ≤50% allowed to characterize two distinct groups with highly divergent outcome. Patients with HRD had significantly shorter median failure-free survival (FFS) (1.1 vs. 5.6 years, p < 0.0001) and overall survival (OS) (2.2 vs. 13.2 years, p < 0.0001) compared to those with LRD. These major differences were confirmed in two validation cohorts from the Italian MCL0208 and the Nordic-MCL4 trials. The results suggest that this subset of HRD patients is not sufficiently managed with the current standard treatment and is asking for novel treatment strategies.

B-28 | Management of Clinical Stent-In-Stent Restenosis (SISR) in High Risk Coronary Artery Disease Patients With Percutaneous Coronary Intervention (PCI) Followed by Coronary Intravascular Brachytherapy (IVBT)

In-stent-restenosis (ISR) is seen in 10% of patients with DES and is often treated with a repeat DES placement. Recurrent ISR or SISR has a high repeat failure rates, requiring target vessel revascularization (TVR). A combination of the presence of multiple layers of stents, previous restenosis, and other additional comorbidities make this patient population complex and higher risk. Angioplasty followed by IVBT is one possible treatment option in the high-risk patients. This study reviewed the efficacy and safety of PCI followed by IVBT for coronary artery disease in high-risk patients experiencing SISR. A retrospective study was performed which reviewed 78 patients treated between 2016-2021 with SISR involving a total of 91 vessels. All patients underwent PCI with balloon angioplasty followed by IVBT. These patients received localized IVBT radiation using the Novoste Beta-Cath System using a strontium-90 isotope. Radiation dose was delivered based on the vessel diameter, with vessels ≥ 3.5mm in diameter receiving 23 Gy, while vessels of <3.5mm in diameter received 18.4 Gy. Major adverse cardiac events (MACE) were defined as all-cause death, myocardial infarction (MI), and stroke. All patients in the cohort had 2 previously placed DESs in the target lesion. Of total 91 treatments, 67% and 33% treatments were delivered to the LAD or the RCA and circumflex vessel or the marginal arteries, respectively. One patient had intraprocedural cardiac arrest due to suspected intracoronary thrombosis. All patients were symptomatic pre-IVBT and 44% experienced symptomatic reduction after treatment. MACE after IVBT includes MI in 18%, stroke in 5%, and all-cause death occurred in 16% of patients at a median time of 9.3 months post treatment with median follow-up being 22.8 months. Of total, 77% retained patency of the irradiated lesion, while 23% percent experienced restenosis requiring TVR. Coronary restenosis post-deployment of multiple layers of DES remains an ongoing challenge in current times. PCI followed by balloon angioplasty with IVBT is a safe and efficacious treatment option for high-risk coronary artery disease patients with SISR, who have very few treatment options otherwise.

New Developments in Systemic Management for High-Risk Early-Stage Hormone-Receptor-Positive, HER2-Negative Breast Cancer

For high-risk early-stage hormone-receptor-positive, HER2-negative breast cancer (HR + /HER2 - EBC), short- and long-term recurrence risks remain substantial despite local control with surgery and radiation and systemic treatment with chemotherapy and endocrine therapy (ET). Recent trials have provided new strategies for reducing recurrence. The monarchE trial demonstrated that adding 2years of adjuvant abemaciclib to ET improves invasive disease-free survival (iDFS) and distant recurrence-free survival (DRFS). In the OlympiA trial for high-risk disease in patients with germline BRCA1/BRCA2 mutations, adding 1year of olaparib to ET improved iDFS, DRFS, and overall survival (OS). In addition, for premenopausal women with high-risk tumors, long-term follow-up of the SOFT, ASTRRA, TEXT, ABCSG-12, and HOBOE trials supports the role of ovarian function suppression (OFS), in combination with adjuvant tamoxifen or aromatase inhibition (AI). For postmenopausal women with high-risk tumors, extended-duration AI for at least 7years should be used with zoledronic acid. Given the remaining recurrence risk even with these interventions and with the ongoing development of new strategies for HR + disease, patients with high-risk EBC should be encouraged to participate in clinical trials, such as trials of immunotherapy, novel oral estrogen receptor alpha (ERα)-targeting agents, antibody-drug conjugates (ADCs), and trials guided by measurements of minimal residual disease (MRD).

Guideline for the Management of Fever and Neutropenia in Pediatric Patients With Cancer and Hematopoietic Cell Transplantation Recipients: 2023 Update.

To update a clinical practice guideline (CPG) for the empiric management of fever and neutropenia (FN) in pediatric patients with cancer and hematopoietic cell transplantation recipients. The International Pediatric Fever and Neutropenia Guideline Panel reconvened to conduct the second update of this CPG. We updated the previous systematic review to identify new randomized controlled trials (RCTs) evaluating any strategy for the management of FN in pediatric patients. Using the Grading of Recommendations Assessment, Development and Evaluation framework, evidence quality was classified as high, moderate, low, or very low. The panel updated recommendations related to initial management, ongoing management, and empiric antifungal therapy. Changes from the 2017 CPG were articulated, and good practice statements were considered. We identified 10 new RCTs in addition to the 69 RCTs identified in previous FN CPGs to inform the 2023 FN CPG. Changes from the 2017 CPG included two conditional recommendations regarding (1) discontinuation of empiric antibacterial therapy in clinically well and afebrile patients with low-risk FN if blood cultures remain negative at 48 hours despite no evidence of marrow recovery and (2) pre-emptive antifungal therapy for invasive fungal disease in high-risk patients not receiving antimold prophylaxis. The panel created a good practice statement to initiate FN CPG-consistent empiric antibacterial therapy as soon as possible in clinically unstable febrile patients. The updated FN CPG incorporates important modifications on the basis of recently published trials. Future work should focus on addressing knowledge gaps, improving CPG implementation, and measuring the impact of CPG-consistent care.

1108. Feasibility and Impact of a Monoclonal Antibody Infusion Program in Reaching Vulnerable Underserved Communities

Abstract Background Monoclonal antibodies (mAbs) against SARS-CoV-2 are potent therapeutics that prevent progression of disease in high-risk patients. Deploying mAb infusion programs and reaching communities in need remains challenging. We established a mAb infusion program centered in the emergency department (ED) fast-track. We seek to assess the feasibility and impact of our mAb infusion program in reaching vulnerable underserved communities. Methods The ED fast-track was repurposed for mAb infusions. Indications and protocols were created by the infectious disease (ID) physician and antimicrobial stewardship program (ASP). Test to treat was deployed in the ED and a referral program connected patients from telehealth and providers in the community to the infusion program (Figure 1). Data on mAb use from November 2020 to February 2022 was reviewed. To assess the reach of the program in vulnerable communities, the COVID-19 Community Vulnerability Index (CCVI) map by zip code was used. The CCVI identifies communities at risk by using variables such as sociodemographic variables, occupational factors, cumulative COVID-19 burden, vaccine uptake and other factors. Figure 1.Monoclonal antibody infusion test-to-treat and referral process in the ED fast track Results mAbs were successfully deployed and sustained throughout the pandemic, increasing its use in each COVID-19 surge by &amp;gt;103% (Figure 2). A total of 267 patients were treated, with an average age of 52 years, of which 55% (147) were female. Ethnicity was 46% Hispanic and Race was 54% White, 28% Black, 1.4% Asian, 1.8% Multiracial and 14% Other. Zip codes by CCVI were 64% high, 18% medium, and 3% low CCVI index. 15% were outside of city limits without CCVI index (Figure 3). Figure 2.COVID-19 Community Vulnerability Index (CCVI) of patients who received monoclonal antibodies at our program Figure 3 Monoclonal antibody infusions by COVID-19 Community Vulnerability Index (CCVI) and Zip codes Conclusion A mAb infusion program with test to treat and referrals from the community was successfully deployed in an ED fast track. The ED space and staff can be leveraged for mAbs during surges amid clinic staffing challenges. The program adopted novel mAbs as new COVID-19 variants emerged. Uptake increased with each wave, likely reflecting awareness of mAbs and the infusion program by patients and providers in the community. The majority of patients served (82%) were of high and medium CCVI. Thus, this mAb infusion program led by ID and ASP successfully reached predominantly underserved vulnerable populations. Disclosures All Authors: No reported disclosures.

Treatment with Sotrovimab and Casirivimab/Imdevimab Enhances Serum SARS-CoV-2 S Antibody Levels in Patients Infected with the SARS-CoV-2 Delta, Omicron BA.1, and BA.5 Variants.

The neutralizing ability of sotrovimab and casirivimab/imdevimab against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is attenuated in the subvariant BA.5. However, the efficacy of sotrovimab in the clinical setting remains to be investigated. Patients admitted to Kishiwada City Hospital with COVID-19 delta, omicron BA.1, or BA.5 subvariants were evaluated retrospectively for serum SARS-CoV-2 S and N antibody levels using the Elecsys Anti-SARS-CoV-2 assay. In patients with COVID-19 during the BA.5 wave of the COVID-19 pandemic, anti-SARS-CoV-2 S antibody titers (median [interquartile range]) increased from 2154.0 (864.0-6669.3) U/mL on day 0 to 21,371.0 (19,656.3-32,225.0) U/mL on day 3 in the group treated with sotrovimab (N = 40) and were significantly higher than in the group treated with remdesivir plus dexamethasone plus baricitinib (p &lt; 0.001). Treatment with sotrovimab could prevent severe disease in high-risk patients infected with SARS-CoV-2 subvariant BA.5.

Outcomes and Management of Sars-CoV2 Omicron Variant in Recipients of Hematopoietic Cell Transplantation (HCT) and CAR-T Therapy

HCT or CAR-T therapy recipients who develop COVID-19 have decreased overall survival (68% Sharma et al. Lancet Haematol. 2021), likely due to disease-inherent and therapy-related immunodeficiency. The development of specific COVID therapies and vaccination during the pandemic has changed the prevention and management of COVID-19 infection. Nevertheless, with the appearance of new SARS-CoV2 variants and omicron, in particular, questions about the severity of disease in high-risk patients are yet to be defined. Methods We included retrospectively 218 adult HCT/CAR-T recipients diagnosed with presumed COVID-19 omicron variant at Memorial Sloan Kettering Cancer Center (MSK), New York, between December 2021 and February 2022. Data were analyzed using SPSS version 26 (IBM, Armonk, NY). Results Among 218 patients, 107 received an autologous HCT, 92 allogeneic HCT, and 19 CAR-T. The median age was 58 years (range, 21 to 87), and 56% were male. The median time from HCT/CAR-T to SARS-CoV2 infection was 44 months (range, 0.1 to 272 months), and 27 patients (12%) acquired SARS-CoV2 within the first 100 days post-HCT/CAR-T. The primary hematologic diagnoses were plasma cell (37%), myeloid (37%), and lymphoid (26%) malignancies. Myeloablative conditioning was performed in 90 patients (41%). In the alloHCT recipients, 17 donors (18%) were matched related, 51 (55%) matched unrelated, 19 (21%) umbilical cord blood, and 5 (6%) haploidentical. 31% patients had 2 or more comorbidities and 9% received IVIG for hypogammaglobulinemia within the prior month. Of note, 40% of the patients were on active cancer therapy (maintenance or treatment) at the time of COVID-19 infection, and 47% of the alloHCT recipients were on GVHD immunosuppressive treatment. Characteristics of COVID-19 omicron variant infection are shown in Table1. Specific COVID-19 treatment was administered in 111 patients (51%) and included MoAbs in 63 patients (56.7%), sotrovimab being the most frequently used (n=55, 87 %), remdesivir (n= 23, 21%), and other antivirals (n= 15, 14%). Risk factors for admission were presence of > 3 comorbidities (HR, 6.2; 95% CI 2.3-16.3, p= 0.000), progression of disease (POD) (HR, 3.8; 95% CI 1.6-8.9, p= 0.002,) and CAR-T therapy (HR 4.5; 95% CI 1.4-14.1p= 0.008). Regarding vaccination status, 84% (n= 183) of the cohort was vaccinated with mRNA Covid-19 vaccines, with 42% of patients having 1 booster before COVID19 infection. Interestingly, only 15/35 (42%) of the booster patients with measured serologic response showed SARS-CoV-19 Antibodies value> 2500 BAU/I. Nineteen patients showed low titer COVID-19 antibodies (<2500 BAU/I) testing after COVID-19 infection: 3 patients died (2 for POD, 1 for COVID), 3 were not vaccinated, 1 patient had to be revaccinated after HCT, and 6 patients were administered tixagevimab/cilgavimab for future prophylaxis. Persistent/Long COVID were present in 8 (3.5%) patients, showing fatigue and URI symptoms 5/8 (62%) had a previous admission for COVID-19 infection and 5/8 (62%) had a negative spike antibody titer before infection. The median duration of viral shedding (positive SARS-CoV-2 PCR) was 11 weeks (range, 3.2 to 19.1 weeks). After a median follow up of 4 months (range, 0 to 8 months), 21 patients (9.6%) had recurrent COVID infection, and two of them died. The overall mortality rate was 10% in all patients (22/218 patients), with 2.5% (6/22) attributable to COVID. Other causes of death were progressive disease (n=13), sepsis (n=1), and hepatic VOD (n=1). Comparing our omicron cohort with the initial 77 HCT & CAR-T patients infected with first wave COVID-19 in March 2020 at our institution, overall survival at 30 days was 94% vs 78% (p=0.010) (Figure 1). Conclusions In our cohort, mortality attributable to the COVID-19 omicron variant was low (2.5%), and only 19% required admission. Risk factors for admission were presence of 3 or more comorbidities, POD at time of COVID infection, and CAR-T therapy. Altogether our date confirms enhanced overall survival (94%) in HCT, and CART recipients infected with the omicron variant of SARS-CoV2 as compared to prior waves of the COVID-19 pandemic. Access to SARS-COV-2 specific treatments and the higher incidence of vaccination in this cohort appear to be key factors to successfully managing patients in order to reduce COVID-19 mortality. Pre-exposure prophylaxis became available later and is also likely important. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Real-World Data on Comparison of Lipid-Lowering Effects between Alirocumab and Evolocumab in Patients with Hypercholesterolemia.

Even though the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, alirocumab and evolocumab, have been approved to reduce plasma low-density lipoprotein cholesterol (LDL-C) and the risk of atherosclerotic cardiovascular disease in high-risk patients, real-world data showing comparisons of the lipid-lowering effects between alirocumab and evolocumab are scarce because of the low prescription rates of PCSK9 inhibitors in clinical practice. Between Feb 2018 and Sep 2021, 22 patients who received alirocumab and 22 patients who received evolocumab at a tertiary medical center were enrolled. The patients' baseline characteristics, prescribed medications, plasma LDL-C levels, and percentages of reduction in LDL-C were compared between alirocumab users and evolocumab users. The alirocumab users more frequently received ezetimibe treatment (72.7% vs. 40.9%, p = 0.03) and had higher baseline LDL-C (165.6 ± 63.2 mg/dL vs. 130.8 ± 56.3 mg/dL, p = 0.04) compared with the evolocumab users. At 6 months of follow-up, the plasma LDL-C levels in the alirocumab users were similar to those in the evolocumab users (79.3 ± 64.0 mg/dL vs. 63.5 ± 44.1 mg/dL, p = 0.48). Additionally, the percentages of LDL-C reduction following treatment were similar between the alirocumab users and evolocumab users (-47.0% ± 45.0% vs. -49.8 ± 24.9%, p = 0.66). The LDL-C lowering effects of alirocumab are similar to those of evolocumab in clinical practice.

To study prevalence of lower extremity arterial disease in high-risk patients by ankle brachial index

To study prevalence of lower extremity arterial disease in high-risk patients by ankle brachial index

The SON2A2 score: A novel grading scale for predicting hemorrhage and outcomes after thrombolysis.

This study aimed to develop a score including novel putative predictors for predicting the risk of sICH and outcomes after thrombolytic therapy with intravenous (IV) recombinant tissue-type plasminogen activator (r-tPA) in acute ischemic stroke patients. All patients with acute ischemic stroke treated with IV r-tPA at three university-based hospitals in Chongqing, China, from 2014 to 2019 were retrospectively studied. Potential risk factors associated with sICH (NINDS criteria) were determined with multivariate logistic regression, and we developed our score according to the magnitude of logistic regression coefficients. The score was validated in another independent cohort. Area under the receiver operating characteristic curve (AUC-ROC) was used to assess the performance of the score. Calibration was evaluated using the Hosmer-Lemeshow goodness-of-fit method. The SON2A2 score (0 to 8 points) consisted of history of smoking (no = 1, yes = 0, β = 0.81), onset-to-needle time (≥3.5 = 1,<3.5=0, β = 0.74), NIH Stroke Scale on admission (>10 = 2, ≤10 = 0, β = 1.22), neutrophil percentage (≥80.0% = 1, <80% = 0, β = 0.81), ASPECT score (≤11 = 2, >11 = 0, β = 1.30), and age (>65 years = 1, ≤65 years = 0, β = 0.89). The SON2A2 score was strongly associated with sICH (OR 1.98; 95%CI 1.675-2.34) and poor outcomes (OR 1.89; 95%CI 1.68-2.13). AUC-ROC in the derivation cohort was 0.82 (95%CI 0.77-0.86). Similar results were obtained in the validation cohort. The Hosmer-Lemeshow test revealed that predicted and observed event rates in derivation and validation cohorts were very close. The SON2A2 score is a simple, efficient, quick, and easy-to-perform scale for predicting the risk of sICH and outcome after intravenous r-tPA thrombolysis within 4.5 h in patients with ischemic stroke, and risk assessment using this test has the potential for early and personalized management of this disease in high-risk patients.

Zone 0 thoracic endovascular aortic repair in high risk patients: A retrospective case series.

To report our experience applying endovascular stent graft repair to treat ascending aortic diseases in high-risk patients and to evaluate the safety and feasibility of this approach. Patients with comorbid conditions or older age are not suitable for open procedures but may be considered suitable for ascending endovascular repair. Eleven high-risk patients received zone 0 thoracic endovascular aortic repair from September 2014 to May 2020. All patients were followed up until death or December 2021. Primary outcomes were in-hospital and long-term all-cause mortality as well as in-hospital and long-term aorta-related mortality. The mean follow-up duration of all patients was 35.78 months. The cohort comprised of three pathology subgroups: penetrating atherosclerotic ulcer (PAU) (n =6), acute dissection (AD) (n = 3), and chronic dissecting aneurysm (CDA) (n = 2). The in-hospital all-cause mortality rates were 0%, 33.33% and 0% for PAU, AD, and CDA groups, respectively. Long-term all-cause mortality were 33.33%, 33.33%, and 50% for PAU, AD, and CDA groups, respectively. There was only one in-hospital death related to acute aortic dissection, and no long-term aorta-related deaths occurred during the study period. During the follow-up time, the majority of patients had good remodeling of ascending aorta, slow progression in cases with endoleak, and no aorta-related mortality. Ascending endovascular aortic repair appears to be a safe and feasible procedure for emergent aortic repair in carefully selected patients with prohibitive surgical risk who are not candidates for open procedures.

ACTIVE SEARCH SCREENING FOR ORAL POTENTIALLY MALIGNANT DISORDERS AND ORAL CANCER AND IN THE CITY OF PIRACICABA

<h3>Objectives</h3> Oral cancer is a world public health problem. Squamous cell carcinoma (SCC) represents approximately 90% of all oral malignancies and is frequently preceded by oral potentially malignant disorders (OPMDs). Screening programs aimed at early detection of oral lesions have been conducted. Therefore, the objective of this research was to carry out an active search screening program in the city of Piracicaba. <h3>Study Design</h3> High-risk patients were identified at the city's health center through their medical records and invited for a dental consultation. Patients who opportunistically sought consultation also attended, and if they did not presented risk factors for SCC they were considered low risk. <h3>Results</h3> Seven hundred fifty-six patients were examined: 445 in the high-risk group and 311 in the low-risk group. Of 33 OPMD and SCC diagnosed, 27 occurred in high-risk patients and 6 in low-risk patients. After chi-square was applied, a statistically significant value (<i>P</i> = .006) for the detection of these diseases in high-risk patients was observed. <h3>Conclusions</h3> It was noted that active search screening focusing on high-risk patients was effective in diagnosing OPMD and SCC, and we encourage its implementation at large scales to reduce the current scenario of this disease.