High-risk Patients Research Articles

Microbiota restoration for recurrent Clostridioides difficile infection.

Since the publication of the recent North American and European guidelines on management of Clostridioides difficile infection (CDI), new evidence describing the epidemiology, testing and treatment of CDI has emerged. Despite all advances in infection control and antibiotic stewardship, the incidence and burden of CDI in the hospitals and the community remains at a stable high. Coupled with the incidence of primary CDI, there is a stable high incidence of recurrent CDI. Testing for primary and recurrent CDI remains a clinical challenge owing to high sensitivity of the PCR (leading to false positives) and somewhat limited sensitivity of EIA for toxin. The pathophysiology of recurrent CDI involves an ongoing disruption of the microbiota owing to the infection and the treatment of CDI employed. Broad spectrum antibiotics such as vancomycin leads to further disruption of microbiota compared to fidaxomicin which has a lower disruption of the microbiota and leads to fewer recurrences. Owing to these data fidaxomicin is considered as the first line antibiotic for recurrent CDI. Intravenous bezlotoxumab is a monoclonal antibody that reduces the risk of recurrence in high-risk patients but does not restore the microbiota. Experimental fecal microbiota transplantation (FMT) has been available for more than a decade. Owing to the success of FMT, two new non-invasive donor dependent Food and Drug Administration (FDA) approved therapies have been available since late 2022. This review summarizes all these conundrums regarding CDI and provides clinical pearls to use in day-to-day practice.

Severe heterotopic ossification after total hip arthroplasty in male patients under 70years of age: effectiveness of prophylactic protocol.

This study aims to evaluate the incidence of clinically significant heterotopic ossification (HO) in primary total hip arthroplasty (THA), comparing outcomes with and without the adoption of an HO prophylactic protocol in male patients under 70years of age. The prophylactic protocol involved the administration of 50mg of Indomethacin twice daily for 3 weeks. HO presence was classified according to the Brooker classification system, considering "severe" clinically significant HO (Brooker grade 3 and 4). Two hundred and seventy-nine patients were included in our study, and an overall HO rate of 68.2% versus a rate of 61.5% was found respectively in patients not subjected and subjected to prophylactic protocol, without significant difference (PR 0.062). However, patients not subjected to the HO prophylactic protocol exhibited a severe HO rate of 22.4% compared to 7.7% in the prophylactic group, with a statistically significant difference (P = 0.008). Our study demonstrated that prophylactic protocol adoption is significantly associated with lower rate of severe HO in male patients under 70years of age. Currently, there are no orthopedic guidelines for the prevention and management of HO after THA, but in the absence of contraindications, the adoption of a prophylactic protocol for HO should always be considered in high-risk patients.

Defining Cardiomyocyte Repolarization Response to Pharmacotherapy in Long-QT Syndrome Type 3.

Long-QT syndrome is a primary cardiac ion channelopathy predisposing a patient to ventricular arrhythmia through delayed repolarization on the resting ECG. We aimed to establish a patient-specific, human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes model of long-QT syndrome type 3 (LQT3) using clustered regularly interspaced palindromic repeats (CRISPR/Cas9), for disease modeling and drug challenge. HiPSCswere generated from a patient with LQT3 harboring an SCN5A pathogenic variant (c.1231G>A; p.Val411Met), and an unrelated healthy control. The same SCN5A pathogenic variant was engineered into the background healthy control hiPSCs via CRISPR/Cas9gene editing to generate a second disease model of LQT3 for comparison with an isogenic control. All 3 hiPSC lines were differentiated into cardiomyocytes. Both the patient-derived LQT3 (SCN5A+/-) and genetically engineered LQT3 (SCN5A+/-) hiPSC-derived cardiomyocytesshowed significantly prolonged cardiomyocyte repolarization compared with the healthy control. Mexiletine, a cardiac voltage-gated sodium channel (NaV1.5) blocker, shortened repolarization in both patient-derived LQT3 and geneticallyengineered LQT3 hiPSC-derived cardiomyocytes, but had no effect in the control. Notably, calcium channel blockers nifedipine and verapamil showed a dose-dependent shortening of repolarization, rescuing the phenotype. Additionally, therapeutic drugs known to prolong the corrected QT in humans (ondansetron, clarithromycin, and sotalol) demonstrated this effect invitro, but the LQT3 clones were not more disproportionately affected compared with the control. We demonstrated that patient-derived and genetically engineered LQT3 hiPSC-derived cardiomyocytesfaithfully recapitulate pathologic characteristics of LQT3. The clinical significance of such an invitro model is in the exploration of novel therapeutic strategies, stratifying drug adverse reaction risk and potentially facilitating a more targeted, patient-specific approach in high-risk patients with LQT3.

Implementation of Liquid Biopsy in Non-Small-Cell Lung Cancer: An Ontario Perspective

Lung cancer is the leading cause of cancer-related deaths in Canada, with non-small-cell lung cancer (NSCLC) accounting for the majority of cases. Timely access to comprehensive molecular profiling is critical for selecting biomarker-matched targeted therapies, which lead to improved outcomes in advanced NSCLC. Tissue biopsy samples are the gold standard for molecular profiling; however, several challenges can prevent timely and complete molecular profiling from being performed, causing delays in treatment or suboptimal therapy selection. Liquid biopsy offers a minimally invasive method for molecular profiling by analyzing circulating tumour DNA (ctDNA) and RNA (cfRNA) in plasma, potentially overcoming these barriers. This paper discusses the outcomes of a multidisciplinary working group in Ontario, which proposed three eligibility criteria for liquid biopsy reimbursement: (1) insufficient tissue for complete testing or failed tissue biomarker testing; (2) suspected advanced NSCLC where tissue biopsy is not feasible; and (3) high-risk patients who may deteriorate before tissue results are available. The group also addressed considerations for assay selection, implementation, and economic impact. These discussions aim to inform reimbursement and implementation strategies for liquid biopsy in Ontario’s public healthcare system, recognizing the need for ongoing evaluation as technology and evidence evolve.

Kidney Outcomes with GLP-1RAs, SGLT2 Inhibitors, DPP-4 Inhibitors, and Sulfonylureas in Type 2 Diabetes and Moderate Cardiovascular Risk

Background: Chronic kidney disease (CKD) is a serious diabetes-related complication. While guidelines recommend use of sodium-glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists to mitigate cardiorenal risk in high-risk patients, the benefit of early initiation of these agents relative to other commonly prescribed glucose-lowering agents in patients at lower baseline cardiovascular disease (CVD) risk remains less clear. Methods: This retrospective observational study emulated an idealized target trial using claims data from OptumLabs® Data Warehouse to test the comparative association of treatment with a dipeptidyl peptidase-4 (DPP-4) inhibitor, SGLT2 inhibitor, GLP-1 receptor agonist, or sulfonylurea on a primary kidney composite outcome of incident CKD stages 3-5, kidney failure, or need for kidney replacement therapy (KRT) in patients with type 2 diabetes (T2D) and moderate CVD risk. A secondary composite outcome included all components of the primary composite outcome plus death. Results: A total of 364,714 adults ≥21 years of age initiating treatment with a DPP-4 inhibitor (N=78,843), GLP-1 receptor agonist (N=42,049), SGLT2 inhibitor (N=45,466), or sulfonylurea (N=198,356) were identified. Relative to DPP-4 inhibitor, SGLT2 inhibitor (HR: 0.71; 95% CI: 0.67-0.74; P˂0.001) and GLP-1 receptor agonist (HR: 0.87; 95% CI: 0.83-0.92; P˂0.001) treatment was superior for the primary composite outcome. Similarly, SGLT2 inhibitor (HR: 0.69; CI: 0.66-0.73) and GLP-1 receptor agonist (HR: 0.86; CI: 0.82-0.91) treatment was associated with risk reductions for the primary outcome relative to sulfonylurea treatment. When comparing SGLT2 inhibitor to GLP-1 receptor agonist therapy, SGLT2 inhibitors were superior for the primary composite outcome (HR: 0.81; 95% CI: 0.75-0.76; P˂0.001). Similar findings were observed for the secondary composite outcome across all comparisons. Conclusions: SGLT2 inhibitors and GLP-1 receptor agonists were superior to DPP-4 inhibitors and sulfonylurea for preventing kidney complications in a T2D population with moderate baseline CVD risk.

Multidimensional analysis of the impact of Gemmatimonas, Rhodothermus, and Sutterella on drug and treatment response in colorectal cancer

BackgroundColorectal cancer is the third most prevalent cancer across the globe. Despite a diversity of treatment methods, the recurrence and mortality rates of the disease remain high. Recent studies have revealed a close association of the gut microbiota with the occurrence, development, treatment response, and prognosis of colorectal cancer.ObjectiveThis study aims to integrate transcriptome and microbiome data to identify colorectal cancer subtypes associated with different gut microbiota and evaluate their roles in patient survival prognosis, tumor microenvironment (TME), and drug treatment response.MethodsAn integrated analysis of microbiome data was conducted on samples of colorectal cancer from public databases. Based on this, two tumor subtypes (C1 and C2) closely associated with patient survival prognosis were identified and a risk score model was constructed. The survival status, clinical parameters, immune scores, and other features were analyzed in-depth, and the sensitivity of various potential drugs was examined.ResultsA thorough examination of microbiome information obtained from colorectal cancer patients led to the identification of two primary tumor clusters (C1 and C2), exhibiting notable variations in survival outcomes. Patients with the C1 subtype were closely associated with better prognosis, while those with the C2 subtype had higher gut microbial richness and poorer survival prognosis. A predictive model utilizing the microbiome data was developed to accurately forecast the survival outcome of patients with colorectal cancer. The TME scores provided a biological basis for risk assessment in high-risk (similar to the C2 subtype) patient cohorts. Evaluation of the sensitivity of different subtypes to various potential drugs, indicated the critical importance of personalized treatment. Further analysis showed good potential of the developed risk-scoring model in predicting immune checkpoint functions and treatment response of patients, which may be crucial in guiding the selection of immunotherapy strategies for patients with colorectal cancer.ConclusionThis study, through a comprehensive analysis of colorectal cancer microbiome, immune microenvironment, and drug sensitivity, enhances the current understanding of the multidimensional interactions of colorectal cancer and provides important clinical indications for improving future treatment strategies. The findings offer a new perspective on improving treatment response and long-term prognosis of patients with CRC through the regulation of microbiota or the utilization of biomarkers provided by it.

Role of 18F-FDG-PET/CT in the initial staging of very high-risk Ewing Sarcoma in a prospective multicentric Phase II Study: Is there still a place for bone marrow sampling?

The Ewing Sarcoma Family of Tumors (ESFT) constitutes a group of rare malignancies, wherein approximately one-third of cases exhibit metastatic spread, particularly impacting prognosis when bone and/or bone marrow (BM) are involved. Primary extra-pulmonary metastatic ESFT often necessitates intensified therapeutic approaches. Accurate staging plays a pivotal role in clinical decision-making, with fluorine-18-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) currently serving as a non-invasive modality for assessing ESFT's BM extent. In the French phase II COMBINAIR3 (NCT03011528) study, a comprehensive approach for patients with extra-pulmonary ESFT metastasis was evaluated. We prospectively compared the efficacy of PET/CT to BM aspiration and biopsy (BMAB) analysis in patients undergoing initial staging. Among the 42 patients analyzed (median age 14 y, 2:1 male/female ratio), 45% presented with pelvic primary tumors and 83% had bone/BM involvement at diagnosis. Our findings showed PET/CT had 100% specificity and 83.3% sensitivity in detecting initial BM involvement. Overall, PET/CT correctly classified 92.8% of patients, reaching 100% accuracy in patients identified with bone involvement, thus surpassing the standard BMAB. These results suggest that the conventional use of BMAB in the initial staging of high-risk ESFT patients can be omitted, promoting PET/CT as a non-invasive alternative, thus improving staging accuracy and treatment decisions in ESFT management.

Prognostic significance of pretreatment PET parameters in inoperable, node-positive NSCLC patients with poor prognostic factors undergoing hypofractionated radiotherapy: a single-institution retrospective study.

Node-positive non-small cell lung cancers (NSCLCs) present a challenge for treatment decisions, particularly in patients ineligible for concurrent chemoradiotherapy (CRT) due to poor performance status and compromised lung function. We aimed to investigate the prognostic value of pretreatment positron emission tomography (PET) parameters in high-risk patients undergoing hypofractionated radiotherapy. A retrospective analysis was conducted on 42 consecutive patients with inoperable node-positive NSCLC, who underwent hypofractionated radiotherapy between 2014 and 2021 at a single institution. Clinical, treatment-related, and [18F]FDG PET-based parameters were correlated with progression-free survival (PFS) and overall survival (OS). Median dichotomisation was performed to establish risk groups. Statistical analyses included univariable and multivariable Cox regression and Kaplan-Meier survival analyses. After a median follow-up of 47.1 months (range: 0.5-101.7), the median PFS and OS were 11.5 months (95% CI: 7.4-22.0), and 24.3 months (95% CI: 14.1-31.8). In univariable Cox regression analysis, significant predictors of PFS included receipt of salvage systemic treatment (p=0.007), SUVmax (p=0.032), and tMTV (p=0.038). Similarly, ECOG-PS (p=0.014), Histology (p=0.046), and tMTV (p=0.028) were significant predictors of OS. Multivariable Cox regression analysis (MVA) identified SUVmax as a significant predictor for PFS [HR: 2.29 (95% CI: 1.02-5.15); p=0.044]. For OS, ECOG-PS remained a significant prognosticator [HR: 3.53 (95% CI: 1.49-8.39); p=0.004], and tMTV approached significance [HR: 2.24 (95% CI: 0.95-5.26); p=0.065]. Furthermore, the high tMTV group exhibited a median PFS of 5.3 months [95% CI: 2.8-10.4], while the low tMTV group had a PFS of 15.2 months [95% CI: 10.1-33.5] (p=0.038, log-rank test). Median OS was 33.5 months [95% CI: 18.3-56.8] for tMTV ≤ 36.6 ml vs. 14.1 months [95% CI: 8.1-27.2] for tMTV > 36.6 ml (p=0.028, log-rank test). Pretreatment PET parameters, especially tMTV, hold promise as prognostic indicators in NSCLC patients undergoing hypofractionated radiotherapy. The study highlights the potential of PET metrics as biomarkers for patient stratification.

Exploring the protective capabilities developed by hospital nurses to deflect workplace violence: a qualitative study in Taiwan.

Workplace violence is a serious safety hazard in the healthcare sector and has attracted much attention worldwide, especially for nursing staff. Equipping nursing personnel with protective capabilities for workplace violence can reduce the risk they face in work settings. This study explored scenarios of common violent patient-nurse conflicts in the workplace of hospital nursing staff and their capabilities for de-escalating such conflicts. We used a qualitative content analysis for this study. Qualitative interviews were conducted with 21 nurses in two teaching hospitals in New Taipei City, Taiwan, until data saturation was reached. The data were transcribed, encoded, and analyzed and similar concepts were grouped under the same category. Four categories of workplace violence scenarios common to hospital nursing staff were identified: unreasonable requests, caring for high-risk patients, long waiting times for medical consultation, and close contact when caring for patients. Two protective capabilities were recognized: communication and interpersonal capabilities and problem-solving skills. Each scenario may require a different combination of abilities. Our findings suggest that a violence-prevention training program could be designed for various workplace violence scenarios to enhance nurses' abilities to de-escalate workplace violence in hospitals.

Effects of asparaginase-associated pancreatitis in children with haematological tumours

BackgroundAsparaginase-associated pancreatitis (AAP) is a major challenge for continuing asparaginase therapy. We aimed to investigate the acute and long-term complications and survival rates related to first and second AAP episodes in Chinese children with haematological malignancies.MethodsWe retrospectively analysed clinical data of children with pancreatitis who received asparaginase chemotherapy for acute lymphoblastic leukaemia (ALL), acute mixed cell leukaemia, and non-Hodgkin’s lymphoma at Shanghai Children’s Medical Center from November 2013 to November 2023.ResultsOf the 76 children included in the study, 12 had local complications (15.79%), with no deaths recorded. Systemic complications manifested in 28 patients (36.84%), resulting in 3 deaths (3.95%). Four patients (5.26%) developed long-term complications (chronic pancreatitis or insulin-dependent diabetes mellitus). No significant differences in local or long-term complications were recorded between children in the asparaginase re-exposed (n=39) and non-re-exposed (n=45) groups. Among the re-exposed patients, eight (25.81%) experienced a second attack without fatalities or complications. Survival analysis of intermediate- to high-risk patients revealed a significantly higher event-free survival (EFS) rate for the re-exposed group than for the non-re-exposed group. The second AAP episode’s occurrence and severity had no relation to the first AAP episode’s severity, and the second AAP episode was significantly less severe than the first (p<0.001).ConclusionsThe second AAP episode’s occurrence is unrelated to the first AAP episode’s severity, and the second AAP episode’s severity is significantly lower than that of the first. Further, asparaginase therapy could improve EFS in children with intermediate and high-risk ALL.

Three-dimensional total body photography, digital dermoscopy, and in vivo reflectance confocal microscopy for follow-up assessments of high-risk patients for melanoma: A prospective, controlled study.

The combination of total body photography (TBP) and digital dermoscopy (DD) for monitoring patients with a high risk for melanoma can allow early detection of melanoma. This study aimed to examine if the use of three-dimensional (3D)-TBP, DD, and reflectance confocal microscopy (RCM) for regular monitoring of patients at high risk for melanoma was beneficial in comparison to monitoring using dermoscopy alone. The intervention group (IG) underwent 3D-TBP examinations at every visit, along with DD and/or RCM for diagnosis and/or monitoring of pigmented lesions if necessary. The control group (CG) underwent dermoscopy examinations alone. A total of 600 patients (324 male and 276 female) were followed-up over a median period of 23 months (mean, 2.85 visits) in the IG and 22 months (mean, 2.74 visits) in the CG (p=0.009). DD and RCM monitoring were performed for 166 and 105 lesions, respectively. The number needed to treat (NNT) to diagnose melanoma with RCM was 2.83. The IG included more second primary melanomas (22 vs. 1, p=0.022) and more excised nevi (186 vs. 10, p<0.001), which consisted of more dysplastic nevi (137 vs. 2, p<0.001). Among the melanomas diagnosed in the IG, three were diagnosed directly with RCM, nine with a combination of 3D-TBP and RCM, and 10 with dermoscopy alone. Follow-up assessments with a combination of 3D-TBP, DD, and RCM led to the detection of more melanomas in comparison to the CG. The use of RCM reduced the NNT for melanocytic lesions.

GAN-Augmented Naïve Bayes for identifying high-risk coronary artery disease patients using CT angiography data.

Coronary artery disease (CAD) is one of the most common cardiovascular disorders affecting millions of individuals globally. It is the leading cause of mortality in both the wealthy and impoverished nations. CAD patients exhibit a wide range of symptoms, some of which are not evident until a major incident occurs. The development of techniques for early detection and precise diagnosis is heavily dependent on research. The proposed system introduces a novel approach, Generative Adversarial Networks Augmented Naïve Bayes (GAN-ANB), to classify high-risk CAD patients using Coronary Computed Tomography Angiography (CCTA) imaging data. The database included images from Coronary Computed Tomography Angiography (CCTA) records of 5,000 individuals. The developed GAN framework consists of a generator to generate synthetic patient profiles, and a discriminator to distinguish between genuine and synthetic profiles to improve the identification of high-risk CAD patients. Adding synthetic data to the training process allowed the discriminator to be utilized further to improve predictive modeling. The performance of the GAN-enhanced prediction model was assessed using accuracy, sensitivity, specificity, and area under the Receiver Operating Characteristic curve (ROC). The model exhibited an outstanding Dice Similarity Coefficient (0.91), Mean Intersection Over Union (0.90), recall (0.96), and precision (0.98) in differentiating between high-risk and low-risk individuals. The identification of high-risk patients with CAD is greatly enhanced by the integration of GANs with clinical and imaging data. ROC of 0.99 was achieved by the GAN-ANB model, which outperformed conventional machine learning models, was achieved using the GAN-ANB model. High cholesterol level, diabetes, and some CCTA-derived imaging characteristics, including plaque load and luminal stenosis, were among the major predictors. This method offers a powerful tool for early diagnosis and intervention, potentially leading to improved patient outcomes and lower healthcare expenditure.

Disseminated cryptococcosis in a child with liver transplantation: a case report

Background. Cryptococcus neoformans causes cryptococcosis, primarily affecting immunocompromised individuals, including solid-organ transplant recipients, and, less frequently, immunocompetent people. Case. A 15-year-old male with congenital hepatic fibrosis, portal hypertension, and cirrhosis underwent orthotopic liver transplantation. He received perioperative antimicrobial and antifungal prophylaxis and continued immunosuppressive treatment. Thirty months post-transplant, he presented with fever, hypertension, and sacroiliac joint pain. Peripheral blood cultures showed C. neoformans, confirmed by pan-fungal polymerase chain reaction assay and latex agglutination tests. Despite initial treatment with intravenous (IV) fluconazole, his condition worsened, necessitating intubation for acute hypoxic respiratory failure. Magnetic resonance imaging and computed tomography scans indicated disseminated cryptococcosis with lymphadenitis, possible meningitis, and pneumonia. Treatment was escalated to IV liposomal amphotericin B and 5-flucytosine, while reducing immunosuppressive treatment. Despite negative fungal cultures on the tenth day, the patient deteriorated, developing pancreatitis, pneumonia, and massive gastrointestinal bleeding, leading to death on the 35th day of hospitalization. Conclusion. This case shows the severity and complexity of managing disseminated cryptococcosis in pediatric liver transplant recipients. Aggressive therapy and early identification are essential for improving outcomes in these high-risk patients.

Lipoprotein Apheresis: Utility, Outcomes, and Implementation in Clinical Practice: A Scientific Statement From the American Heart Association.

Despite the availability of multiple classes of lipoprotein-lowering medications, some high-risk patients have persistent hypercholesterolemia and may require nonpharmacologic therapy. Lipoprotein apheresis (LA) is a valuable but underused adjunctive therapeutic option for low-density lipoprotein cholesterol and lipoprotein(a) lowering, particularly in children and adults with familial hypercholesterolemia. In addition to lipid lowering, LA reduces serum levels of proinflammatory and prothrombotic factors, reduces blood viscosity, increases microvascular myocardial perfusion, and may provide beneficial effects on endothelial function. Multiple observational studies demonstrate strong evidence for improved cardiovascular outcomes with LA; however, use in the United States is limited to a fraction of its Food and Drug Administration-approved indications. In addition, there are limited data regarding LA benefit for refractory focal segmental glomerulosclerosis. In this scientific statement, we review the history of LA, mechanisms of action, cardiovascular and renal outcomes data, indications, and options for treatment.

A machine learning algorithm-based risk prediction score for in-hospital/30 day mortality after adult cardiac surgery.

A study of the performance of in-hospital/30 day mortality risk prediction models using an alterantive machine learning algorithm(XGBoost) in adults undergoing cardiac surgery. Retrospective analyses of prospectively routinely collected data on adult patients undergoing cardiac surgery in the UK(UK) from January 2012 to March 2019.Data was temporally split 70:30 into training and validation subsets. Independent mortality prediction models were created using sequential backward floating selection(SBFS) starting with 61 variables. Assessments of discrimination, calibration and clinical utility of the resultant XGBoost model with 23 variables were then conducted. 224,318 adults underwent cardiac surgery during the study period with a 2.76%(N = 6,100) mortality. In the testing cohort, there was good discrimination(AUC 0.846, F1 0.277) and calibration(especially in high-risk patients). Decision curve analysis showed XGBoost-23 had a greater net benefit till a threshold probability of 60%.The most important variables were the type of operation, age, creatinine clearance, urgency of the procedure and the New York Heart Association score. Feature-selected XGBoost showed good discrimination, calibration and clinical benefit when predicting mortality post-cardiac surgery. Prospective external validation of a XGBoost-derived model performance is warranted.

Pharmaco-Economic Assessment of Screening Strategies for High-Risk MASLD in Primary Care.

Several scientific associations recommend a sequential combination of non-invasive tests (NITs) to identify high-risk MASLD patients but their cost-effectiveness is unknown. A cost-utility model was developed to assess the incremental cost-effectiveness ratio (ICER) of recommended screening strategies for patients with clinically suspected MASLD, specifically those with type 2 diabetes (T2D) and obesity with multiple cardiometabolic risk factors which will be initiated in primary care. Six screening strategies were assessed, using either vibration-controlled transient elastography (VCTE) or the enhanced liver fibrosis (ELF) test as a second-line test following an initial Fibrosis-4 (FIB-4) assessment as the first line NIT. The model included treatment effects of resmetirom for metabolic dysfunction-associated steatohepatitis (MASH) patients with F2 or F3 fibrosis. All screening strategies for high-risk MASLD in US incurred additional costs compared to no screening, ranging from $13 587 to $14 730 per patient with T2D and $14 274 to $15 661 per patient with obesity. However, screening reduced long-term costs, ranging from $22 150 to $22 279 per patient with T2D and $13 704 to $13 705 per patient with obesity, compared to $24 221 and $14 956 for no screening, respectively. ICERs ranged from $26 913 to $27 884 per QALY for T2D patients and $23 265 to $24 992 per QALY for patients with obesity. While ICERs were influenced by VCTE availability, they remained cost-effective when using ELF as the second-line test. Our findings remain robust across a range of key parameters. Screening for high-risk MASLD is cost-effective according to recent guidelines. Implementing these screening strategies in primary care should be considered.

Hybrid Surgical treatment of thoraco-abdominal aneurysm: case report

The conventional surgical treatment of TAAA is complex and is associated with important perioperative mortality and mobidity. There is consensus that endovascular aneurysm repair (EVAR) is the preferred treatment for high-risk patients, but the availability of endovascular-branched grafts are quite limited. As an alternative for such dilema, the hybrid approach came as another possibility for high risk patients where totally endovascular treatment is not feasible and clinical condition for convencional surgery is prohibitive. Thus, the objective of this study is to report our service's experience with the hybrid surgical technique for treatment of this severe condition. Male patient, 73 years old, diagnosed with fusiform aortic aneurysm at the thoracoabdominal transition level, measuring 10.1 x 8.9 cm, associated with a large retroperitoneal hematoma, likely corresponding to an aneurysm rupture. The hybrid strategy was chosen, involving two stages: conventional surgery and endovascular procedures. However, approximately 24 hours after the first surgery the patient had refractory cardiac arrest at intensive care unit. Surgical treatment of thoracoabdominal aneurysm is a complex issue, and the trend over time is tending toward total endovascular treatment, and these devices will undoubtedly evolve and be used more and more in the years to come. However, the hybrid repair will likely remain a standard procedure for a while, until total endovascular procedures become more common and the necessary endovascular materials widely available.

The use of interleukin-10 (IL-10) and phosphorus levels as predictors of the time to improvement in COVID-19 patients: a prospective study

AbstractEarly detection of COVID-19 improves the chance of recovery and helps identify high-risk patients. Our study aimed to statistically predict the time to improvement with the admission data of COVID-19 patients.Methods: Our prospective cohort study occurred between January and September 2022 at Alexandria University Hospital’s outpatient clinic and isolation department. We enrolled 43 patients after assessing their eligibility and collecting their baseline data.Results: The mean age was 34.8 years (± 12.3). Most of them were females (65.1%). The mean of oxygen saturation was 95.2% (± 2.8). We used linear regression to predict how long it would take to improve [time to improvement (days) = 1.186*P (mmol/L) + 0.010*IL-10 (pg/mL)]. Its diagnostic performance was 0.723 (95% CI: 0.552–0.894), and it was accurate at predicting improvement within a week but not at longer delays; additionally, its positive and negative predictive values were 56.3% and 85.2%, respectively.Conclusion: We recommend monitoring phosphorus and interleukin-10 levels. The time-to-improvement delay negatively correlated with a reduction in baseline oxygen saturation upon admission. Additionally, for every 0.84 meq/L increase in phosphorus or 100 pg/mL increase in interleukin-10, there was a 1-day delay provided that the other was constant, with a coefficient of determination of 85.9%.

Bifurcated Endografts for the Treatment of Aortoiliac Disease a Systematic Review and Individual Patient Data (IPD) Meta-Analysis.

This review aimed to assess the efficacy and safety of bifurcated endografts in the treatment of aortoiliac disease (AOID). A systematic search on PubMed, Scopus, and Web of Science was performed. The primary endpoint was primary patency, whereas secondary endpoints included reintervention, technical, clinical success, and overall postoperative complications. Ten studies with a total of 365 patients were included in this review. Most included studies used the AFX unibody endograft, one study the Excluder endograft, and one the Powerlink endograft. The majority of included patients displayed TransAtlantic InterSociety Consensus (TASC) D aortoiliac lesions (56.1% 205/365). The pooled primary patency estimates at 12, 24, and 36 months were 93.93% (95% confidence interval [CI]: 87.7-100), 91.46% (95% CI: 84.6-98.8), and 90.25% (95% CI: 82.6-98.6), respectively. The mean primary patency time was 85.74 months (95% CI: 71.99-86.88). The pooled freedom from reintervention estimates at 12, 24, and 36 months were 91.94% (95% CI: 81.4-100), 91.03% (95% CI: 79.8-100), and 91.03% (95% CI: 79.8-100), respectively. The pooled estimates of major complications (rupture, graft thrombosis, amputation) were 11.12% (95% CI, 0.05%-3.03%), 3.76% (0.32%-9.45%), and 0.38% (0%-2.59%), whereas the pooled estimates for minor complications (hematoma, groin infection, dissection) and overall mortality were 5.27% (95% CI, 1.11%-11.38%), 6.93% (95% CI, 2.94%-12.16%), 2.19% (95% CI, 0.06%-6.14%), and1.57% (95% CI, 0.13-3.97), respectively. Technical and clinical success estimates were 99.92% (95% CI: 98.86%-100%) and 99.47% (95% CI: 94.92%-100%), respectively. The application of bifurcated endografts may present a safe and viable option in the treatment of AOID, with preliminary results indicating promising primary patency outcomes. However, the definitive assessment of their efficacy and safety will be better determined through long-term follow-up studies and high-quality randomized controlled trials, which are essential to substantiate these initial findings. Bifurcated endograft application may be a safe and viable alternative for high-risk patients with complex AOID TASC C and D lesions with encouraging primary patency outcomes potentially comparable to those of open surgery. Non-negligible postoperative complication rates were also noted. High-quality randomized controlled trials and studies comparing CERAB, kissing stenting, and the use bifurcated endografts for the treatment of AOID is necessary to draw more definite conclusions.

12344 Four-Month Delay In Denosumab Induced Severe Hypocalcemia And Hypophosphatemia. Case Report

Abstract Disclosure: M.M. Eid: None. S. Reutrakul: None. Introduction: Denosumab is a fully human monoclonal antibody that binds to the receptor activator of nuclear factor kappa Β ligand, blocks osteoclast function and reduces bone resorption. Case: A 91 year old male with history of osteoporosis, type 2 diabetes, chronic kidney disease (CKD) and prostate cancer. Presented with fatigue and cold intolerance. Denied confusion, muscle cramp, perioral numbness/tingling, bowel habit change. Medications included empagliflozin 12.5 mg/day, leuprorelin 45 mg every 6 months since 2021 and cholecalciferol 1000IU/day. On examination, he was alert and oriented x 3 with stable vital signs. No thyromegaly. Chvostek's sign was negative. Labs: serum calcium (Ca) 6.5 mg/dl, corrected Ca (Co Ca) 6.7mg/dl(N 8.7-10.4), ionized Ca 0.7mMol/l (N 1.13-1.32), TSH 131uIU/ml (N 0.55-4.78), free T4 0.72ng/dl (N 0.89-1.76), creatinine 1.55mg/dl, GFR 42ml/min/1.73m2, HbA1C 6.1%. EKG with corrected QT interval of 499 msec. Hypocalcemia work up : parathyroid hormone (PTH) 762 pg/ml (N 18.4-80.1), 25 OH vitamin D (Vit D) 37ng/ml (N 30-100), 1,25 OH Vit D 77pg/ml (N 18-72), phosphorus (Phos) 1mg/dl (N 2.4-5.1), magnesium (Mag) 1.7mg/dl (N 1.6-2.6),ALP 59U/L(N 45-117). Clinical impressions were a new diagnosis of primary hypothyroidism and non PTH mediated hypocalcemia with secondary hyperparathyroidism. A thorough review of medication revealed that he received the first dose of denosumab 60 mg 4 months prior to this presentation. Baseline labs 1 month prior to denosumab: Ca/Co Ca 9.1/9.2mg/dl, Phos 4.5mg/dl, PTH 199.6pg/ml, Mag 2.1mg/dl,TSH 2.72 uIU/ml. 2 months after denosumab administration, serum Ca/Co Ca 8.8/8.6mg/dl. He was admitted and received Ca gluconate 2gm IV pushes, calcitriol 0.5 mcg/day and levothyroxine 50 mcg/day and kept on cardiac monitoring. He remained asymptomatic. On the 5th day, serum Ca/Co Ca 8.4/8.6mg/dl, Phos 3mg/dl, Mag 2mg/dl. He was discharged on oral Ca Carbonate, calcitriol and levothyroxine. The second denosumab dose was cancelled. Conclusion: Denosumab is an effective anti-osteoporotic medication but can cause hypocalcemia. The risks for denosumab induced hypocalcemia include renal impairment, Vit D deficiency and lack of Ca/Vit D supplementation. Hypocalcemia usually occurs 1 - 2 weeks after denosumab, corresponding to its peak of action. Checking serum Ca and Vit D with correction of deficiencies before starting denosumab is recommended. In high risk patients with CKD, daily Ca and Vit D supplements are recommended (1). Our case has CKD and developed severe hypocalcemia and hypophosphatemia 4 months after receiving denosumab without other apparent causes for hypocalcemia. Hypothyroidism is likely an incidental diagnosis and not contributing to hypocalcemia in the absence of rhabdomyolysis. Reference: 1.Jalleh R, Basu G, Leu RL, Jesudason S: Denosumab induced severe hypocalcemia in chronic kidney disease. Case Rep Nephrol.2018 Presentation: 6/2/2024