Cardiovascular Risk in Patients with Chronic Hepatitis C Treated with Direct Acting Antivirals.

Background: Chronic hepatitis C (CHC) is associated with hepatic and extrahepatic complications, including cardiovascular disease (CVD). The effects of sustained virological response (SVR) and liver fibrosis on CVD risk are not well established. Aims: We aim to assess the dynamics of Fibrosis-4 (FIB-4) and Atherosclerotic Cardiovascular Disease 2013 (ASCVD) scores up to three years after direct acting antivirals (DAA) treatment and explore the time-dependent association between the two scores. Methods: We included consecutive CHC patients treated with DAA and followed up with them for three years. Outcomes were changes from baseline (before DAA) in ASCVD and FIB-4 scores, measured at the end of treatment, 12-, 24-, and 36-months follow-up. Results: In total, 91 patients with CHC were finally included (median age: 66 years (IQR = 58−72 years); 43% females). Median follow-up was 2 years (1−3 years) and all patients reached SVR. The ASCVD score did not significantly change from baseline (Mean = 17.2%, 95% CI 14.1, 20.3), but the FIB-4 score significantly decreased at any time-point by an average of 0.8 (95% CI 0.78, 0.82, p < 0.001). Elevated FIB-4 scores at one (ß = 1.16, p < 0.001) and three years (ß = 2.52, p < 0.001) were associated with an increased ASCVD score. Clinically, two participants- with non-decreasing FIB-4 scores after treatment- had acute coronary syndrome at the end of treatment and one year follow-up, respectively. Conclusions: In our study, we found that FIB-4 and ASCVD scores exhibited a positive correlation irrespective of time-point after treatment. Larger studies are essential to further investigate the utility of FIB-4 scores in cardiovascular risk assessment.

Diagnostic and infection control strategies for Clostridioides difficile infections in a setting of high antimicrobial resistance prevalence.

Clostridioides difficile (CD) is a major nosocomial pathogen and the leading cause of antibiotic-associated diarrhoea. In light of the strong association between antimicrobial use and CD infections (CDI), it may be hypothesised that areas at higher prevalence of antimicrobial resistance, like the region of Campania in southern Italy, could also have a higher rate of CDI. In this multicentre, region-based, prospective study, we analysed such issues, exploiting CDI incidence data collected from local hospitals. In 2016, the Italian National Centre for Disease Control supported a project involving three Italian regions: Friuli Venezia Giulia, Lazio and Campania. In Campania, a network of 49 hospitals willing to participate in the project was created. The project consisted of two phases: a survey on practice patterns concerning CDI and an epidemiological surveillance study. We identified a stringent need to improve awareness about CDI among the regional health-care community, as a widespread lack of surveillance programmes for CDI control was observed (existing in only 40% of participating facilities). Moreover, almost half of the participating hospitals (n=16, 43%) had no standardised procedures or protocols to control and prevent CDI. In the second phase of the study, we collected data of CDI cases during a six-month surveillance programme. In all, 87 CDI cases were observed, for a total of 903,334 patient bed-days and 122,988 admissions. According to the above data, CDI incidence was 0.96 cases/10000 patient bed-days, much lower than expected based on prior studies conducted elsewhere. The results of our study suggest CDI remains a rather neglected clinical issue in Campania. Despite a high burden of antimicrobial resistance and antimicrobial use in our geographic setting, we observed a very low incidence of CDI. Such a low incidence could be explained by underdiagnosis, but could also be related to actual diet, the lower patient age or the specific genetic background. However, further studies are warranted to either confirm or rebut the above hypotheses.

Multidrug-Resistant Infections and Outcome of Critically Ill Patients with Coronavirus Disease 2019: A Single Center Experience.

Background: The aim of this study was to assess the drivers of multidrug-resistant (MDR) bacterial infection development in coronavirus disease 2019 (COVID-19) and its impact on patient outcome. Methods: Retrospective analysis on data from 32 consecutive patients with COVID-19, admitted to our intensive care unit (ICU) from March to May 2020. Outcomes considered were MDR infection and ICU mortality. Results: Fifty percent of patients developed an MDR infection during ICU stay after a median time of 8 [4-11] days. Most common MDR pathogens were carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii, causing bloodstream infections and pneumonia. MDR infections were linked to a higher length of ICU stay (p = 0.002), steroid therapy (p = 0.011), and associated with a lower ICU mortality (odds ratio: 0.439, 95% confidence interval: 0.251-0.763; p < 0.001). Low-dose aspirin intake was associated with both MDR infection (p = 0.043) and survival (p = 0.015). Among MDR patients, mortality was related with piperacillin-tazobactam use (p = 0.035) and an earlier onset of MDR infection (p = 0.042). Conclusions: MDR infections were a common complication in critically ill COVID-19 patients at our center. MDR risk was higher among those dwelling longer in the ICU and receiving steroids. However, MDR infections were not associated with a worse outcome.

Anthropometric parameters and liver histology influence lipid metabolic changes in HCV chronic hepatitis on direct-acting antiviral treatment.

BACKGROUND: Hepatitis C virus (HCV) infection affects lipid metabolism. We investigated the impact of direct-acting antiviral (DAA) treatment on lipid metabolism in chronic hepatitis C (CHC), with a focus on the effects of anthropometric parameters and liver histology. We also analyzed the dynamics of metabolic indexes used to estimate cardiovascular risk. METHODS: In 49 patients with CHC treated with DAAs, lipid metabolic changes, anthropometric parameters, liver histology and cardiovascular risk indexes, including triglyceride to HDL ratio (Tr/HDL), fatty liver index (FLI) and visceral adiposity index (VAI) were evaluated at baseline (BL), end of treatment (EOT) and 12 [sustained virological response (SVR) 12] and 24 (SVR24) weeks after EOT. RESULTS: SVR occurred in 96% of cases. Total and LDL cholesterol and ApoB levels increased significantly between BL and EOT (P<0.001, <0.001 and 0.05, respectively) and remained stable thereafter. Total and LDL cholesterol significantly increased only in patients with higher BL waist circumference (P<0.01 and 0.009), fibrosis (P=0.002 and 0.005) and steatosis (P=0.043 and 0.033, respectively). HDL cholesterol significantly rose at SVR24. However, cardiovascular risk indexes (Tr/HDL ratio, FLI and VAI) did not significantly change during DAA treatment and follow up. CONCLUSIONS: Patients with HCV eradication after DAA treatment develop a pro-atherogenic lipid pattern, which varies according to anthropometric parameters and liver histology. However, no increase of cardiovascular risk indexes occurs in the short-term. Total and LDL cholesterol should be monitored long-term in CHC patients cured from infection.

Effect of immunosuppression maintenance in solid organ transplant recipients with COVID-19: Systematic review and meta-analysis.

BACKGROUND: The aim of this study was to assess the effect of continuing immune suppressive therapy in solid organ transplant recipients (SOTR) with coronavirus disease 2019 (COVID-19). METHODS: Systematic review and meta-analysis of data on 202 SOTR with COVID-19, published as case reports or case series. We extracted clinical, hemato-chemical, imaging, treatment, and outcome data. RESULTS: Most patients were kidney recipients (61.9%), males (68.8%), with median age of 57 years. The majority was on tacrolimus (73.5%) and mycophenolate (65.8%). Mortality was 18.8%, but an equal proportion was still hospitalized at last follow up. Immune suppressive therapy was withheld in 77.2% of patients, either partially or completely. Tacrolimus was continued in 50%. One third of survivors that continued immunosuppressants were on dual therapy plus steroids. None of those who continued immunosuppressants developed critical COVID-19 disease. Age (OR 1.07, 95% CI 1-1.11, P = .001) and lopinavir/ritonavir use (OR 3.3, 95%CI 1.2-8.5, P = .013) were independent predictors of mortality while immunosuppression maintenance (OR 0.067, 95% CI 0.008-0.558, P = .012) and tacrolimus continuation (OR 0.3, 95% CI 0.1-0.7, P = .013) were independent predictors of survival. CONCLUSIONS: Our data suggest that maintaining immune suppression might be safe in SOTR with moderate and severe COVID-19. Specifically, receiving tacrolimus could be beneficial for COVID-19 SOTR. Because of the quality of the available evidence, no definitive guidance on how to manage SOTR with COVID-19 can be derived from our data.

Cold reperfusion before rewarming reduces neurological events after deep hypothermic circulatory arrest.

OBJECTIVES: To identify a safety threshold of deep hypothermic circulatory arrest (DHCA) duration; to determine which protection offers the best outcome and whether a 10-min period of cold perfusion (20°C) preceding rewarming can reduce neurological events (NE). METHODS: From January 1988 to April 2009, 456 patients underwent aortic surgery using DHCA: for chronic disease in 239 and acute in 217. Cerebral protection was obtained by straight DHCA (sDHCA) in 69 cases, retrograde perfusion (RCP) in 198 and antegrade perfusion (ACP) in 189. In 247 subjects, a 10-min period of cold perfusion (20°C) preceded rewarming; in 209 rewarming was restarted without this preliminary. RESULTS: Fifty-eight patients (13%) experienced NE. Twenty-two (5%) suffered temporary neurological dysfunction (TND) and 36 (8%) suffered stroke. DHCA duration >30 min was predictive for higher rate of NE (25.2% vs. 2.0%, P 0.001); after this value, only ACP was able to reduce incidence of NE (16.5% vs. 30.5%, P = 0.035). Cold reperfusion before rewarming significantly reduced incidence of NE (7.7% vs. 18.7%, P < 0.001) and extended the safe period to 40 min. Thirty-day mortality was 16.0%. Predictors of higher early mortality were acute aortic disease, longer DHCA, lack of ACP or prompt rewarming when DHCA >30 min and postoperative stroke. CONCLUSIONS: sDHCA remains a safe and easy tool for cerebral protection when DHCA duration is expected to be less than 30 min. When aortic surgery requires a longer period, ACP should be instituted. Before rewarming, a 10-min period of cold perfusion significantly reduces incidence of NE.

Thyrocervical trunk pseudoaneurysm following central venous catheterization.

A 71-year-old female developed a painless neck mass three months following an aortic valve replacement, mitral commissurotomy, and coronary artery bypass. A cervical trunk angio revealed a pseudoaneurysm supplied from a branch of the thyrocervical trunk, which was successfully excised.

Bilateral internal thoracic artery on the left side: a propensity score-matched study of impact of the third conduit on the right side.

OBJECTIVE: This study was undertaken to evaluate long-term results of bilateral internal thoracic artery grafting with saphenous vein or another arterial conduit as the third conduit. METHODS: From September 1991 to December 2002, a total of 1015 patients underwent first isolated coronary artery bypass grafting for triple-vessel disease, with bilateral internal thoracic artery plus saphenous vein in 643 cases and bilateral internal thoracic artery plus arterial conduit in 372. A nonparsimonious regression model was built to determine propensity score, then sample matching (saphenous vein vs arterial conduit) was performed to select 885 patients (590 with saphenous vein, 295 with arterial conduit). Groups had similar preoperative and operative characteristics. RESULTS: Eight-year freedoms from cardiac death were significantly higher when saphenous vein was used (98.6% +/- 0.5% with saphenous vein vs 95.3% +/- 1.3% with arterial conduit, P = .009), but this difference was related exclusively to right gastroepiploic artery grafting (94.5% +/- 1.6% vs saphenous vein, P = .004). This difference disappeared for radial artery grafting (97.6% +/- 1.6% vs saphenous vein, P = .492). Cox analysis confirmed that supplementary gastroepiploic artery was an independent variable for lower freedoms from all-cause mortality and from cardiac death. Presence of high-degree stenosis (80%) appeared to influence this result. CONCLUSIONS: In patients with triple-vessel disease undergoing first isolated coronary artery bypass grafting, supplementary venous grafts seem to provide more stability than gastroepiploic artery, which may even impair long-term outcome.

Mitral valve surgery for functional mitral regurgitation: prognostic role of tricuspid regurgitation.

BACKGROUND: The purpose of this study was to evaluate the impact of untreated moderate-or-more functional tricuspid regurgitation (FTR) on mid-term outcome of patients with functional mitral regurgitation (FMR) undergoing mitral valve surgery (MVS). METHODS: From January 1988 to April 2003, 165 patients having FMR underwent MVS with untreated FTR. Patients with organic mitral or tricuspid valve disease were excluded. The entire population was divided into two groups, group A: 102 patients (FTR 0/1+), group B: 63 patients (FTR 2+/3+). No statistical difference was found between two groups concerning preoperative and operative variables. MV was repaired in 137 and replaced in 28 cases; the impact of untreated moderate-or-more FTR was estimated by Cox analysis. RESULTS: Thirty-day mortality was 6.7 (5.9% group A vs 7.9% group B, p=0.607). Five-year actuarial survival was 73.5% (66.6-80.4%); 88.2% (83.0-93.4%) group A versus 46.0% (33.7-58.3%) group B, p<0.001; the possibility to be alive in NYHA class I-II was 65.8% (58.4-73.2%); 78.4% (72.3-84.5%) group A versus 41.2% (29.1-53.3%) group B, p<0.001. Cox analysis confirmed the impact of untreated moderate-or-more FTR on 5-year survival (HR=3.1, 95% CI=1.8-5.1, p<0.001) and possibility to be alive in NYHA class I-II (HR=3.0, 95% CI=1.8-4.9, p<0.001). After a median interval time of 28 months (IQR=11-60), TR grade was echocardiographically assessed in 122 (79.2%) of 154 patients surviving the first month. In group A (87 patients), TR grade decreased significantly from 0.7+/-0.5 to 0.3+/-0.5 (p<0.001) in the early postoperative period. Then, it increased again to 0.6+/-0.7 at follow-up (p<0.001); no difference was found between preoperative and follow-up time (p=ns). In group B (35 cases), TR grade decreased significantly from 2.2+/-0.4 to 1.3+/-0.7 in the early postoperative period (p<0.001), but then increased again to 2.2+/-0.9 (p<0.001 vs postoperative value; p=0.838 vs preoperative value). Cox analysis confirmed that the progression of TR grade at follow-up is a risk factor for lower survival and possibility to be alive in NYHA class I-II. CONCLUSIONS: Patients with untreated moderate-or-more FTR had survival and survival in NYHA class I-II lower than patients with untreated less-than-moderate FTR at 5-year follow-up.

Mitral valve surgery for functional mitral regurgitation: should moderate-or-more tricuspid regurgitation be treated? a propensity score analysis.

BACKGROUND: The aim of this retrospective study was to evaluate the clinical outcome of treating or not treating moderate-or-more functional tricuspid regurgitation in patients with functional mitral regurgitation undergoing mitral valve surgery. METHODS: From January 1988 to March 2003, 110 patients with functional mitral regurgitation undergoing mitral valve surgery showed moderate-or-more functional tricuspid regurgitation, which was treated (group T) in 51 and untreated in 59 (group UT) patients. Propensity score was used to adjust midterm results. The tricuspid valve was always repaired using the DeVega technique. The mitral valve was repaired in 84 and replaced in 26 patients; no residual moderate-or-more functional mitral regurgitation was assessed at hospital discharge. RESULTS: Thirty-day mortality was 5.5% (8.5% for group UT versus 2% for group T; p= 0.245). Adjusted 5-year survival was 45.0% +/- 6.1% in group UT and 74.5% +/- 5.1% in group T (p= 0.004), whereas the possibility to be alive in New York Heart Association class I or II was 39.8% +/- 6.0% in group UT versus 60.0% +/- 6.5% in group T (p= 0.044). Proportional Cox analysis, forcing propensity score into the model, demonstrated that untreated moderate-or-more tricuspid regurgitation was a risk factor for lower midterm survival (hazard ratio, 2.7; 95% confidence interval, 1.3 to 5.4) and survival in New York Heart Association class I or II (hazard ratio, 1.9; 95% confidence interval, 1.1 to 3.4). Follow-up functional tricuspid regurgitation progression rate (3+/4+) was 5% in group T versus 40% in group UT (p < 0.001). The progression of functional tricuspid regurgitation grade at follow-up was a risk factor for worse survival and the possibility to be alive in New York Heart Association class I or II. CONCLUSIONS: Tricuspid annuloplasty is an easy and safe procedure, mandatory in case of at least moderate functional tricuspid regurgitation to achieve better mid-term outcome in patients with functional mitral regurgitation undergoing mitral valve surgery.

Impact of ischemic mitral regurgitation on long-term outcome of patients with ejection fraction above 0.30 undergoing first isolated myocardial revascularization.

BACKGROUND: We evaluated the impact of ischemic mitral regurgitation (IMR) on long-term outcome of patients with an ejection fraction (EF) exceeding 0.30 undergoing isolated coronary artery bypass grafting (CABG). METHODS: From November 1994 to December 2002, 4226 patients (EF > 0.30) underwent a first isolated CABG. Preoperative IMR was present in 1421 (33.6%, group IMR), of which 1254 had mild (1/4) and 167 had moderate (2/4). The remaining 2805 patients (66.4%, group no-IMR) showed no IMR. A nonparsimonious regression model was built to determine the propensity score. Ten-year freedom from death from any cause, cardiac death, and cardiac events was evaluated by the Kaplan-Meier method. Results of Cox analysis were adjusted by entering the propensity score as an independent variable. RESULTS: All patients had similar early mortality (2.1% no-IMR vs 2.5% IMR, p = 0.502) and morbidity (6.5% no-IMR vs 6.6% IMR, p = 0.840). In patients with EF of 0.31 to 0.40, but not in those ones with EF exceeding 0.40, IMR grade was an independent variable for worse long-term freedom from cardiac death (82.8 +/- 3.2 vs 91.4 +/- 2.4; Cox hazard ratio [HR], 2.1 [95% confidence interval (CI), 1.1 to 4.1]; p = 0.0324) and cardiac events (78.6 +/- 3.5 vs 88.5 +/- 2.7; Cox HR, 2.0 [95% CI, 1.1 to 3.7]; p = 0.0174). CONCLUSIONS: Mild or moderate IMR in patients with an EF exceeding 0.30 undergoing first isolated CABG influences long-term outcome when EF is 0.31 to 0.40, but not when it exceeds 0.40.

Does off-pump coronary surgery reduce postoperative acute renal failure? The importance of preoperative renal function.

BACKGROUND: Off-pump was compared with on-pump coronary artery bypass graft surgery to evaluate the impact of cardiopulmonary bypass on the incidence of postoperative acute renal failure (ARF). METHODS: From November 1994 to December 2001, 2,943 patients having multivessel surgical disease underwent myocardial revascularization. Ninety patients were excluded because of incompleteness of data, intraoperative death, or preoperative chronic dialysis. The analysis was split: one analysis included 1,724 (862 each group) of 2,618 patients with normal preoperative creatinine (<1.5 mg/dL), and the second analysis included 160 (80 each group) of 215 patients with preoperative abnormal renal function; in both analyses matched groups were selected applying propensity score. RESULTS: In the group with normal preoperative creatinine, the incidence of 30-day ARF was 5.4% (2.9% off-pump versus 7.9% on-pump; p < 0.001). Stepwise logistic regression confirmed that cardiopulmonary bypass was an independent variable for increased postoperative ARF incidence (odds ratio, 3.3), as well as age and reduced left ventricular ejection fraction. Receiver operating characteristic curves showed that cardiopulmonary bypass duration was a predictor of higher ARF incidence (area under the curve, 0.79) with a cutoff value of 66 minutes. In the patients with abnormal renal function preoperatively, the incidence of ARF was similar between the groups (16.3% on-pump versus 12.5% off-pump; p = 0.499). Acute renal failure had an important impact on early (odds ratio, 3.6) and late mortality (hazard ratio, 4.1). CONCLUSIONS: Off-pump surgery plays an important renoprotective role and provides better early and late outcome in patients with normal preoperative creatinine. When the preoperative creatinine is abnormal, the surgical strategy does not seem to have any influence. The occurrence of ARF significantly impairs early and long-term mortality, and the surgical strategy does not improve outcomes.

Partial clamping of the brachiocephalic trunk for total ascending aorta replacement without circulatory arrest: early and midterm results.

BACKGROUND: The aim of this study was to evaluate in elective patients the early and midterm results of partial clamping of the brachiocephalic trunk (BCT) for total ascending aorta replacement (TAAR) without circulatory arrest. Contraindications to the procedure were BCT/aortic arch calcifications and chronic aortic dissection. METHODS: The right radial artery was cannulated to monitor the systemic pressure after the BCT was partially clamped. A specially designed clamp was applied obliquely to occlude approximately 50% of the BCT and part of the aortic arch. The distal tip of the clamp was positioned in front of the left subclavian artery. From January 2002 to October 2003, 92 patients underwent TAAR. In 62 patients (67.4%), partial clamping of the BCT was used. Twenty of these patients underwent isolated TAAR, 27 underwent aortic valve replacement and TAAR, 11 had a Bentall operation, and 2 had a Cabrol operation. The aortic valve was spared in the remaining 2 patients. The mean (+/- SD) aortic cross-clamping and cardiopulmonary bypass times were 96 +/- 31 minutes and 116 +/- 43 minutes, respectively. RESULTS: Early mortality was 1.6% (1 patient). No cerebrovascular accidents occurred, demonstrating the safety of the technique. The major complications were acute respiratory insufficiency in 2 cases and acute renal failure in 5. The mean follow-up time was 9.0 +/- 6.5 months. The mean 18- month and event-free survival rate was 96.6% +/- 0.9%. CONCLUSION: Partial clamping of the BCT for TAAR without circulatory arrest provides good early and midterm clinical results. Aortic arch clamping is not associated with cerebrovascular accidents.