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Objectives: The aim of this study was to perform a budget impact analysis (BIA) of introducing olaparib treatment for adult patients with metastatic castration-resistant prostate cancer in Argentina., Methods: A BIA model was used to estimate the cost difference between the current scenario (without olaparib) and the new scenario (incorporation of olaparib) for a third-party payer over a 5-year time horizon. The budgetary impact is estimated at the national health system level and by healthcare sectors in Argentina. Input parameters were obtained from the literature and validated by local expert opinion. Direct medical costs were obtained from both the Institute for Clinical Effectiveness and Health Policy (IECS) unit cost database and public data in Argentina. The microcosting estimation was used for key variables of the analysis. All costs are reported in US dollars (US$) as for October 2022 (1 US$ = 152.59 Argentine pesos). One-way sensitivity analyses and scenario analyses were conducted to evaluate the model robustness., Results: The incorporation of olaparib, with a wholesale price per pack of US$3176, was associated with a weighted average of the budget impact per member per month (PMPM) of US$0.0191 for the national health system, being slightly higher than the estimated budgeted high impact threshold (US$0.0153). The PMPM budget impact for a 5-year average ranged between US$0.007 (public sector) and US$0.033 (private sector). The duration of treatment with olaparib was the most influential parameter in the budget impact results., Conclusions: The introduction of olaparib for the treatment of metastatic castration-resistant prostate cancer has a high budget impact for Argentina's health system. These findings are informative to support policy decisions aimed to expand the current treatment landscape for prostate cancer., (© 2024. The Author(s).)

Objective.: Motivation for the study. Treatment options for HER2-positive breast cancer were evaluated, focusing on the efficacy and safety of trastuzumab-emtansine (T-DM1) compared to other anti-HER2 therapies. Main findings. Trastuzumab-deruxtecan (T-DXd) and PyroCap emerged as promising alternatives, showing substantial improvements in progression-free survival for locally advanced or metastatic breast cancer. T-DM1 showed superior efficacy to the other treatments. Implications. Our findings could inform healthcare decision-making processes to optimize strategies for HER2-positive breast cancer, and potentially improve health outcomes and quality of life. We aimed to study the efficacy and safety of trastuzumab-emtansine (T-DM1) versus other anti-HER2 therapies in HER2+ breast cancer (BC)., Materials and Methods.: We performed a network meta-analysis (NMA) of randomized controlled trials (RCTs). Our study focused on patients undergoing treatment for unresectable locally advanced breast cancer (LABC) or metastatic breast cancer (mBC), which included regimens involving trastuzumab and taxanes. Additionally, we considered cases within the first 6 months of treatment for HER2+ early breast cancer (EBC)., Results.: A total of 23 RCTs and 41 reports were included in our analysis. LABC and mBC showed no statistically significant difference in any of the comparisons of T-DM1 versus the other anti-HER2+ therapies. When assessing progression-free survival (PFS), trastuzumab-deruxtecan (T-DXd) and PyroCap demonstrated greater efficacy compared to other treatments (Hazard Ratio [HR]: 3.57; 95% confidence interval [CI]: 2.75-4.63 and HR: 1.82; 95% CI: 1.35-2.44; respectively), while T-DM1 alone exhibited superior effectiveness compared to LapCap (HR: 0.65; 95% CI: 0.55-0.77), TrasCap (HR: 0.65; 95% CI: 0.46-0.91), LapCapCitu (HR: 0.60; 95% CI: 0.33-1.10), Nera (HR: 0.55; 95% CI: 0.39-0.77), and Cap (HR: 0.37; 95% CI: 0.28-0.49)., Conclusions.: NMA allows a ranking based on the comparative efficacy and safety among the interventions available. Although superior to other schemes, T-DM1 showed a lower efficacy performance in PFS and overall response rate and a trend towards worse overall survival than T-DXd.

Objectives: To comprehensively identify and map an exhaustive list of value criteria for the assessment of next-generation sequencing/comprehensive genomic profiling (NGS/CGP), to be used as an aid in decision making., Methods: We conducted a systematic review to identify existing value frameworks (VFs) applicable to any type of healthcare technology. VFs and criteria were mapped to a previously published Latin American (LA) VF to harmonize definitions and identify additional criteria and or subcriteria. Based on this analysis, we extracted a comprehensive, evidence-based list of criteria and subcriteria to be considered in the design of a NGS/CGP VF., Results: A total of 42 additional VFs were compared with the LA VF, 88% were developed in high-income countries, 30% targeted genomic testing, and 16% specifically targeted oncology. A total of 242 criteria and subcriteria were extracted; 227 (94%) were fully/partially included in the LA VF; and 15 (6%) were new. Clinical benefit and economic aspects were the most common criteria. VFs oriented to genomic testing showed significant overlap with other VFs. Considering all criteria and subcriteria, a total of 18 criteria and 36 individual subcriteria were identified., Conclusions: Our study provides an evidence-based set of criteria and subcriteria for healthcare decision making useful for NGS/CGP as well as other health technologies. The resulting list can be beneficial to inform decision making and will serve as a foundation to co-create a multistakeholder NGS/CGP VF that is aligned with the needs and values of health systems and could help to improve patient access to high-value technologies., Competing Interests: Author Disclosures Author disclosure forms can be accessed in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

Alcoholic liver disease (ALD) is a major cause of chronic liver disease. This term covers a broad spectrum of liver lesions, from simple steatosis to alcoholic hepatitis and cirrhosis. The pathogenesis of ALD is multifactorial and not fully elucidated due to complex mechanisms related to direct ethanol toxicity with subsequent hepatic and systemic inflammation. The accumulation of pro-inflammatory cytokines and the reduction of anti-inflammatory cytokines promote the development and progression of ALD. To date, there are no targeted therapies to counter the progression of chronic alcohol-related liver disease and prevent acute liver failure. Corticosteroids reduce mortality by acting on the hepatic-systemic inflammation. On the other hand, several studies analyzed the effect of inhibiting pro-inflammatory cytokines and stimulating anti-inflammatory cytokines as potential therapeutic targets in ALD. This narrative review aims to clarify the role of the main cytokines involved in the pathogenesis and treatment of ALD.

Introduction and Objectives: The liver imaging reporting data system (LI-RADS) for hepatocellular carcinoma (HCC) was proposed to standardize and enhance consensus of reporting. However, clinical utility of LI-RADS has not been evaluated in Latin America. We therefore sought to compare LI-RADS categories with histopathology findings in liver transplant (LT) explants in a regional center., Materials and Methods: Prospective cohort study conducted between 2012 and 2018 in a single center from Argentina including patients with HCC listed for LT. LI-RADS definitions were applied to magnetic resonance images (MRI) or computed tomography (CT) abdominal scans at time of listing and at final pre-LT reassessment and compared to explant pathology findings; specifically, major nodule (NOD1)., Results: Of 130 patients with HCC listed for LT (96.1% with cirrhosis and 35.6% with hepatitis C virus infection), 72 underwent LT. Overall, 65% had imaging HCC diagnosis based on MRI (n = 84), 26% with CT (n = 34) and 9% (n = 12) with both methods. Among LT patients with pre-transplant imaging at our institution (n = 42/72), 69% of the NOD1 were LR-5, 21% LR-4 and 10% LR-3. Definite HCC diagnosis was 50% in LR-3 NOD1 (CI 18-90); none presented microvascular invasion. In LR-4 NOD1, HCC was confirmed in 89% (CI 59-98), of which 11% showed microvascular invasion; whereas in LR-5 NOD1 77% (CI 64-87) had confirmed HCC, 17% with microvascular invasion., Conclusions: LI-RADS was useful to standardize reports; however, no significant differences were observed between LR-4 and LR-5 HCC probability when compared to explant pathology., (Copyright © 2020 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Controversy exists whether NE after LT are more frequently observed in children or adults. We aimed to compare the incidence and outcomes for NE after LT in pediatric and adult recipients. A single-center cohort study, including all LT between 2001 and 2013, was performed. Definition of NE included impaired consciousness, delirium, seizures, focal neurologic deficit, visual impairment, or slurred speech. A cohort of 443 consecutive LT recipients was included: 307 adults and 136 children. Cumulative incidence of NE was similar between adults 15% (n = 41) and children 16% (n = 20; P = .73) with a complete neurological recovery in 62% and 95% of the patients, respectively (P < .0001). Adults with NE had significantly lower survival (70% vs 76%; P = .015) with a HR of 2.36; this was similarly observed in children (45% vs 66%; HR 2.05, CI 0.66; 6.34). Independent risk factors for NE in adults were pre-LT ascites, delta sodium, and post-LT hypomagnesemia, whereas in children pre-LT encephalopathy ≥II and serum albumin were associated with NE. Although a similar incidence of NE after LT was observed, children were more likely to achieve neurological recovery. Risk factors for the development of NE are difficult to assess in both populations., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: The association between data of right heart catheterization and cardiac allograft vasculopathy (CAV) in adult heart transplant (HTx) recipients remains to be determined., Methods and Results: This is an observational, retrospective study, including all consecutive asymptomatic HTx patients undergoing routine right and left catheterization. The independent predictive power of pulmonary capillary wedge pressure (PCWP) to predict CAV (classified according to working formulation of a standardized nomenclature for CAV-2010) was the primary end point. Seventy-one patients were included, with a mean time from HTx to procedure of 19 ± 25 months. At coronary angiography first degree of CAV was found in eight patients (11.2%), second degree of CAV in two patients (2.8%), and third in two (2.8%). PCWP values were significantly higher in patients with CAV compared with patients without CAV (17.5 ± 7.5 vs. 10.4 ± 5.6, P < 0.001) and values of 15 mmHg or greater had an AUC of 0.71 (0.48-0.92), with a sensitivity of 71% and a specificity of 73% in predicting CAV, with an independent relationship confirmed at logistic regression analysis (odds ratio 1.28, IC 1.06-1.53; P = 0.008)., Conclusion: A significantly elevated PCWP at the time of the diagnosis of transplant coronary artery disease may be considered as an early marker of CAV, especially in asymptomatic HTx recipients.

Coronary artery disease represents the leading cause of death for HIV patients treated with highly active antiretroviral treatment. Besides this, an extensive amount of data related to the risk of overt heart failure and consequently of atrial fibrillation and sudden cardiac death (SCD) in this population has been reported. It seems that persistent deregulation of immunity in HIV-infected patients is a common pathway related to both of these adverse clinical outcomes. Despite the fact that atrial fibrillation and heart failure are relatively common in HIV, few data are reported about screening, diagnosis, and potential treatment of these conditions.

Introduction: Thirty-day readmission rates after percutaneous coronary intervention (PCI) have been related to adverse prognosis, and represent one of the most investigated indicators of quality of care. These data, however, derive from non-European centers evaluating all-cause readmissions, without stratification for diagnosis., Methods: All consecutive patients undergoing PCI at our center from January 2009 to December 2011 were enrolled. Thirty-day readmissions related to postinfarction angina, myocardial infarction, unstable angina or heart failure were defined as acute coronary syndrome (ACS) or heart failure rehospitalizations. Major cardiac adverse event (MACE) was the primary outcome, and its single components (death, myocardial infarction and repeated revascularization) the secondary ones., Results: A total of 1192 patients were included; among them, 53 (4.7%) were readmitted within 30 days, and 25 (2.1%) were classified as ACS/heart failure related. During hospitalization, patients with ACS/heart failure readmissions were more likely to suffer a periprocedural myocardial infarction (22 vs. 4%; P = 0.012), and to undergo PCI at 30 days (52 vs. 0.5%; P < 0.001). Logistic regression analysis indicated that periprocedural myocardial infarction represented the only independent predictor of an ACS/heart failure readmission [odds ratio (OR) 4.5; 1.1-16.8; P = 0.047]. After a median follow-up of 787 days (434-1027; first and third quartiles), patients with a 30-day ACS/heart failure readmission experienced higher rates of MACE, all-cause death and myocardial infarction (64 vs. 21%, P < 0.001; 28 vs. 6%, P = 0.017; and 20 vs. 2.7%, P < 0.001, respectively). Cox multivariate analysis indicated that ACS/heart failure 30-day readmissions were independently related to an increased risk of all-cause death (OR 3.3; 1.1-8.8; P = 0.02), differently from 30-day non-ACS/heart failure readmissions (OR 3.1; 0.7-12.9; P = 0.12)., Conclusion: Thirty-day readmissions after PCI in an Italian center are infrequent, and only those patients with ACS/heart failure show a detrimental impact on prognosis who have periprocedural myocardial infarction as the only independent predictor.

Background: Appropriate management for patients with multivessel coronary disease presenting with ST segment Elevation Myocardial Infarction (STEMI) remains to be defined., Methods and Results: Medline and Cochrane Library were searched for randomized controlled trials (RCTs) or observational studies adjusted with multivariate analysis, reporting about STEMI patients with multivessel coronary disease treated with either a culprit only or complete revascularization strategy, excluding patients in cardiogenic shock. Prespecified analysis was performed according to the strategy of complete revascularization, either during the same procedure of primary percutaneous coronary intervention (PCI) or during the index hospitalization. MACE (a composite and mutually exclusive end point of death or myocardial infarction or revascularization) at follow-up of at least one year was the primary end point. 9 studies with 4686 patients compared culprit only versus complete PCI performed during the primary PCI. Rates of MACE did not differ at 90 days (OR 0.70 [0.38, 1.27], I(2)=0%) or at 1 year (1-2.5) (OR 0.70 [0.47, 1.03], I(2)=0%). No significant difference was found for the components of the primary outcome, apart from a reduction in repeated revascularization for patients undergoing complete PCI during the STEMI procedure (OR 0.62 [0.39, 0.98], I(2)=0%). 6 studies (1 RCT) with 5855 patients compared culprit only lesions versus complete PCI performed during index hospitalization. 90 day risk of MACE did not differ nor 1 year (1-2.5) MACE (OR 0.86 [0.62, 1.08], I(2)=0%), with a similar reduction in repeated revascularization (0.60 [0.40, 0.90], I(2)=0%)., Conclusions: Complete revascularization performed during primary PCI or index hospitalizations for patients presenting with STEMI appears safe at short term follow-up and offers a reduction in repeated revascularization at one year., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Transcatheter aortic valve implantation (TAVI) may be performed using the transfemoral (TF) or transapical (TA) approach in most patients with aortic stenosis. The impact of access choice on peri-procedural and midterm results remains to be defined., Methods: Medline and Cochrane Library were searched for articles describing differences in baseline, peri-procedural, and midterm outcomes among patients undergoing TF or TA TAVI. The primary end-point was all-cause mortality after at least 1-year follow-up, while secondary end-points were 30 days mortality and in-hospital complications (bleeding and cerebrovascular events). The independent impact of access choice was evaluated with pooled analysis using a random-effect model., Results: Thirteen studies with 10,468 patients were included. TF was the most exploited strategy (69.5% vs. 30.5%). After adjusting for confounding variables, 30-day and midterm follow-up mortality (median 365 days, range 222-400) were lower in TF patients with a pooled adjusted odds ratio of 0.81 (0.68-0.97 I(2) 99%) and 0.85 (0.80-0.90 I(2) 96%), respectively. Regarding periprocedural outcomes, TF reduced risk of bleedings and strokes (OR of 0.74 [0.66-0.82 I(2) 95%] and 0.91 [0.83-0.99] I(2) 86%, respectively)., Conclusions: The TF approach reduces mortality in TAVI patients, due to lower rates of periprocedural bleedings and strokes., (© 2014, Wiley Periodicals, Inc.)

Several clinical and procedural factors have been identified as predictors of early and midterm events after transcatheter aortic valve implantation (TAVI), but incidence and prognostic impact of diabetes mellitus (DM), especially insulin treated, on short- and midterm outcomes remain to be defined. All consecutive patients who underwent TAVI at our institutions were enrolled and stratified according to DM status. All-cause mortality at 30 days or in hospital and at follow-up was the primary end point, whereas periprocedural complications, rates of myocardial infarction, stroke, and reintervention at follow-up were the secondary ones. All end points were adjudicated according to the Valve Academic Research Consortium definitions. In all, 511 patients were enrolled: 361 without DM, 78 with orally treated DM, and 72 with insulin-treated DM. Orally treated DM patients were more frequently women, whereas insulin-treated DM patients were younger. Thirty-day Valve Academic Research Consortium mortality was not significantly higher in patients with orally treated DM and insulin-treated DM compared with patients without diabetes (6.4%, 9.7%, and 4.7%, p = 0.09). Bleedings, vascular complications, postprocedural acute kidney injury, and periprocedural strokes were not significantly different in the 3 groups. At midterm follow-up (median 400 days), patients with insulin-treated DM had a significantly higher mortality rate (33.3% vs 18.6%, p = 0.01) and higher myocardial infarction incidence (8.3% vs 1.4%, p = 0.002) if compared with patients without diabetes. Strokes and reinterventions at follow-up were similar in the 3 groups. After multivariable adjustment, insulin-treated DM was independently correlated with death (hazard ratio 2, 95% confidence interval 1.3 to 3.3) and myocardial infarction (hazard ratio 3.73, 95% confidence interval 1.1 to 13). In conclusion, DM does not significantly affect rates of complications in patients who underwent TAVI. Insulin-treated DM, but not orally treated DM, is independently associated with death and myocardial infarction at midterm follow-up and should be included into future TAVI-dedicated scores., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: Despite encouraging short-term and mid-term results, transcatheter aortic valve implantation (TAVI) interventions are still burdened from high rates of adverse events, stressing the need for accurate predictive risk instruments. We compared available surgical risk scores to describe unfavorable outcomes after TAVI., Methods: The Age, Creatinine, and Ejection fraction (ACEF) score, the logistic Euroscore, and the Society of Thoracic Surgeons Mortality score (STS) were appraised for their independent power of prediction and for their accuracy (C-index) to predict 30-day and medium-term mortality, according to the Valve Academic Research Consortium., Results: Nine hundred and sixty-two patients were included. All the scores demonstrated a moderate positive correlation. The closest correlation was observed between the STS score and Euroscore. After logistic regression analysis, STS score and Logistic Euroscore provided independent prediction for short-term all-cause mortality [P = 0.02, odds ratio (OR) 1.1; 95% confidence interval (CI) 1.06-1.31 and P = 0.027, OR 1.03; 95% CI 1.01-1.405]. For in-hospital complications, only STS score performed significantly (P = 0.005, OR 1.05; 95% CI 1.01-1.06). ACEF, Euroscore, and STS score showed low accuracy for 30-day all-cause mortality (area under the curve 0.6, 0.44-0.75; vs. 0.53, 0.42-0.61; vs. 0.62, 0.52-0.71, respectively), whereas STS score performed better for in-hospital complications (0.59, 0.55-0.64). Moreover, after Cox-multivariate adjustments, only ACEF score was near to significance to predict all-cause mortality at mid-term (OR 1.7; 0.8-2.9; P = 0.058), showing the highest accuracy (0.63, 0.55-0.71)., Conclusion: In TAVI patients, ACEF score, STS score and Logistic Euroscore provided only a moderate correlation and a low accuracy both for 30-day and medium-term outcomes. Dedicated scores are needed to properly tailor time and kind of approach.

Aim: Many randomized trials have compared coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) in terms of efficacy, but data comparing outcomes of patients in which these two techniques have failed are lacking., Methods: We included patients undergoing PCI at our center between July 2002 and December 2004. Subjects were distinguished in 2 groups: those with at least one occluded or stenotic saphenous vein graft (CABG failure), and those with at least one stent with angiographically documented restenosis (PCI failure). The primary endpoint was the long-term rate of major adverse clinical events., Results: Two hundred and thirthy four patients were included, with a medium follow up of 61±13 months; 134 were assigned to the CABG failure group, and 104 to the PCI failure group, sharing high rates of baseline risk factors. At long term rates of death were higher in post CABG group (22.1% vs. 9.9%; P=0.015, RR 2.24 C.I. 95% 1.14-4.40) while death rates in patients with diagnosis of diabetes mellitus (24.0% vs. 23.5%; P=0.969, RR 1.020 C.I. 95% 0.38-2.74) were not different, Conclusion: PCI can be safely offered to both these kinds of patients: as recently demonstrated post CABG outcomes seem to be more favorable in patients with diabetes mellitus.