Feasibility and accuracy of the screening for diabetic retinopathy using a fundus camera and an artificial intelligence pre-evaluation application.

AIMS: Periodical screening for diabetic retinopathy (DR) by an ophthalmologist is expensive and demanding. Automated DR image evaluation with Artificial Intelligence tools may represent a clinical and cost-effective alternative for the detection of retinopathy. We aimed to evaluate the accuracy and reliability of a machine learning algorithm. METHODS: This was an observational diagnostic precision study that compared human grader classification with that of DAIRET®, an algorithm nested in an electronic medical record powered by Retmarker SA. Retinal images were taken from 637 consecutive patients attending a routine annual diabetic visit between June 2021 and February 2023. They were manually graded by an ophthalmologist following the International Clinical Diabetic Retinopathy Severity Scale and the results were compared with those of the AI responses. The main outcome measures were screening performance, such as sensitivity and specificity and diagnostic accuracy by 95% confidence intervals. RESULTS: The rate of cases classified as ungradable was 1.2%, a figure consistent with the literature. DAIRET® sensitivity in the detection of cases of referable DR (moderate and above, "sight-threatening" forms of retinopathy) was equal to 1 (100%). The specificity, that is the true negative rate of absence of DR, was 80 ± 0.04. CONCLUSIONS: DAIRET® achieved excellent sensitivity for referable retinopathy compared with that of human graders. This is undoubtedly the key finding of the study and translates into the certainty that no patient in need of the ophthalmologist is misdiagnosed as negative. It also had sufficient specificity to represent a cost-effective alternative to manual grade alone.

Efficacy of cefiderocol- vs colistin-containing regimen for treatment of bacteraemic ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii in patients with COVID-19.

INTRODUCTION: Ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) in patients hospitalized in intensive care units (ICUs) is an important and challenging complication, including in patients with coronavirus disease 2019 (COVID-19). Considering the poor lung penetration of most antibiotics, including intravenous colistin due to the poor pharmacokinetics/pharmacodynamics at the infection site, the choice of the best antibiotic regimen is still being debated. METHODS: This single-centre, observational study was conducted from March 2020 to August 2022, and included all patients hospitalized consecutively with VAP and concomitant bloodstream infection due to CRAB in the COVID-ICU. The main goal of the study was to evaluate risk factors associated with survival or death at 30 days from VAP onset. A propensity score for receiving therapy was added to the model. RESULTS: During the study period, 73 patients who developed VAP and concomitant positive blood cultures caused by CRAB were enrolled in the COVID-ICU. Of these patients, 67 (91.7%) developed septic shock, 42 (57.5%) had died at 14 days and 59 (80.8%) had died at 30 days. Overall, 54 (74%) patients were treated with a colistin-containing regimen and 19 (26%) were treated with a cefiderocol-containing regimen. Cox regression analysis showed that chronic obstructive pulmonary disease and age were independently associated with 30-day mortality. Conversely, cefiderocol-containing regimens and cefiderocol + fosfomycin in combination were independently associated with 30-day survival, as confirmed by propensity score analysis. CONCLUSIONS: This real-life study in patients with bacteraemic VAP caused by CRAB provides useful suggestions for clinicians, showing a possible benefit of cefiderocol and its association with fosfomycin.

Target-controlled infusion during MitraClip procedures in deep-sedation with spontaneous breathing.

OBJECTIVE: Percutaneous mitral valve repair with the MitraClip system is an alternative procedure for high-risk patients not suitable for conventional surgery. The MitraClip can be safely performed under general anesthesia (GA) or deep sedation (DS) with spontaneous breathing using a combination of propofol and remifentanil. This study aimed to evaluate the benefits of target-controlled infusion (TCI) of remifentanil and administration of propofol during DS compared with manual administration of total intravenous anesthesia (TIVA) medication during GA in patients undergoing MitraClip. We assessed the impact of these procedures in terms of remifentanil dose, hemodynamic profile, adverse events, and days of hospital stay after the process. PATIENTS AND METHODS: From March 2013 to June 2015 (mean age 73.5 ± 9,54), patients underwent transcatheter MitraClip repair, 27 received DS via TCI and 27 GA with TIVA. RESULTS: Acute procedural success was 100%. DS-TCI group, in addition to a significant reduction of remifentanil dose administrated (249 µg vs. 2865, p < 0.01), resulted in a decrease in vasopressor drugs requirement for hemodynamic adjustments (29.6% vs. 63%, p = 0.03) during the procedure and a reduction of hypotension (p = 0.08). The duration of postoperative hospitalization did not differ between the two groups (5.4 days vs. 5.8 days, p = 0.4). CONCLUSIONS: Administration of remifentanil by TCI for DS in spontaneously breathing patients offers stable anesthesia conditions, with a lower amount of drugs, higher hemodynamic stability, and decreased side effects.

Local gentamicin-collagen sponge reduces cardiovascular implantable electronic device infections and pocket hematoma.

OBJECTIVE: Implantation or replacement of a cardiovascular implantable electronic device (CIED) may be associated with complications, such as pocket hematomas and infections. This study aims to determine whether a lyophilized gentamycin-containing collagen implant (GCCI) reduces major CIED infections and pocket hematomas after implant. SUBJECTS AND METHODS: A retrospective study was conducted among patients who underwent implantation or replacement of CIED at the Tor Vergata Polyclinic (Rome, Italy) between June 2007 and November 2019. The primary combined endpoint was infection and hematoma occurrence through 12 months of follow-up post-procedure. The rate of single infectious complications, pocket hematomas or both were also assessed. RESULTS: We compared 475 patients treated with the GCCI (GCCI group) with 714 patients who did not receive it (control group). Complications occurred in 127 patients (11%); a statistically significant reduction of infections and pocket hematomas in the GCCI group was reported when compared with control patients (1% vs. 17%; p<0.0001). A total of 20 (2%) infectious events were reported, 102 (8%) patients developed a pocket hematoma, and 5 (0.4%) had both. The rate of single complications was significantly lower in GCCI group: infection 0.2% vs. 2.6% (p=0.002), pocket hematoma 0.6% vs. 13.8% (p<0.001). The association between antiplatelet/anticoagulation therapy and hematoma development was not statistically significant. CONCLUSIONS: The GCCI is a medical device that can be used in addition to local hemostasis and prophylactic doses of systemic antibiotics with the aim of reducing infective complications and pocket hematoma after permanent CIED implantation or replacement.

CDK12 promotes tumorigenesis but induces vulnerability to therapies inhibiting folate one-carbon metabolism in breast cancer.

Cyclin-dependent kinase 12 (CDK12) overexpression is implicated in breast cancer, but whether it has a primary or only a cooperative tumorigenic role is unclear. Here, we show that transgenic CDK12 overexpression in the mouse mammary gland per se is sufficient to drive the emergence of multiple and multifocal tumors, while, in cooperation with known oncogenes, it promotes earlier tumor onset and metastasis. Integrative transcriptomic, metabolomic and functional data reveal that hyperactivation of the serine-glycine-one-carbon network is a metabolic hallmark inherent to CDK12-induced tumorigenesis. Consistently, in retrospective patient cohort studies and in patient-derived xenografts, CDK12-overexpressing breast tumors show positive response to methotrexate-based chemotherapy targeting CDK12-induced metabolic alterations, while being intrinsically refractory to other types of chemotherapy. In a retrospective analysis of hormone receptor-negative and lymph node-positive breast cancer patients randomized in an adjuvant phase III trial to 1-year low-dose metronomic methotrexate-based chemotherapy or no maintenance chemotherapy, a high CDK12 status predicts a dramatic reduction in distant metastasis rate in the chemotherapy-treated vs. not-treated arm. Thus, by coupling tumor progression with metabolic reprogramming, CDK12 creates an actionable vulnerability for breast cancer therapy and might represent a suitable companion biomarker for targeted antimetabolite therapies in human breast cancers.

Antithrombotic therapy management in a man with ST elevation myocardial infarction and triple positive antiphospholipid syndrome: case report and literature review.

OBJECTIVE: Antiphospholipid syndrome (APS) is a systemic autoimmune disorder associated with vascular complications including acute myocardial infarction (AMI). AMI pathogenesis in APS is considered to be acute thrombosis of coronary arteries, in contrast to typical AMI where the pathogenesis is atherosclerotic plaque rupture. Therapeutic management is therefore a clinical challenge. There is no consensus among experts about optimal antithrombotic therapy in secondary prevention. The role of coronary stents is still to be determined, due to the higher rates of stent thrombosis after percutaneous coronary intervention (PCI) in APS patients. CASE REPORT: We described the case of a 51-year-old male, smoker, that presented with anterior ST elevation myocardial infarction (STEMI) as first manifestation of APS. The patient underwent primary PCI on left main and ostial left anterior descending artery. RESULTS: We discussed antithrombotic therapy management after PCI in our patient and reviewed literature on current therapeutic management of this specific population. CONCLUSIONS: APS patients with STEMI should undergo PCI, usually associated with thrombus aspiration, and in select cases stent implantation in the culprit lesion. In the latter case, triple antithrombotic therapy with short-term dual antiplatelet therapy and long-term anticoagulant therapy is recommended. Clinicians should include autoimmune etiologies in the differential diagnosis of underlying causes of AMI.

Excimer laser technology in percutaneous coronary interventions: Cardiovascular laser society's position paper.

Excimer Laser Coronary Atherectomy (ELCA) is a well-established therapy that emerged for the treatment of peripheral vascular atherosclerosis in the late 1980s, at a time when catheters and materials were rudimentary and associated with the most serious complications. Refinements in catheter technology and the introduction of improved laser techniques have led to their effective use for the treatment of a wide spectrum of complex coronary lesions, such as thrombotic lesions, severe calcific lesions, non-crossable or non-expandable lesions, chronic occlusions, and stent under-expansion. The gradual introduction of high-energy strategies combined with the contrast infusion technique has enabled us to treat an increasing number of complex cases with a low rate of periprocedural complications. Currently, the use of the ELCA has also been demonstrated to be effective in acute coronary syndrome (ACS), especially in the context of large thrombotic lesions.

Recycling agricultural, municipal and industrial pollutant wastes into fertilizers for a sustainable healthy food production.

This work was focused on recycling different typology of pollutant wastes (olive pomace and orange residues; municipal wastes and sulphur residue of hydrocarbon refining processes) with the triple objectives of limiting wastes in landfill, reducing greenhouse gas emission and producing organic-mineral fertilizers. The environmental risks and benefits of the whole process have been considered. The specific objectives were: 1) innovation in waste management techniques by reducing the accumulation of different typology of wastes using a unique process 2) verifying efficiency of the obtained organic-mineral fertilizers on soil and plant growth 3) improving soil and crop quality relating wastes to food, economy and environment. Sulphur-based pads improved soil quality mostly when contained orange residues. Onion and Garlic grew better in presence of sulphur-based pads (+20%), and mostly when pads contained orange residues (+45%). Onion and Garlic quality, in terms of antioxidant compounds and antioxidant capacity, increased in presence of sulphur-based pads (+30%) mostly when orange residues were present in the pads (+90%). In short, in addition to the environmental advantages, numerous economic benefits coming from the decrease in the production and use of chemical fertilizers, the reduction of costs for landfilling and the gain rising from the sale of the new fertilizers produced, emerged.

Anatomic features in SCAD assessed by CCT: A propensity score matching case control study.

PURPOSE: Spontaneous coronary artery dissection (SCAD) may occur in middle age population without any cardiovascular risk factor. We retrospectively evaluated anatomic features of 11 patients with SCAD using a coronary arteries computed tomography (CCT), compared to age and sex balanced patients who underwent CCT. MATERIAL AND METHODS: CCT was performed in 11 patients (7 females and 4 males) as follow-up in patients with SCAD (left anterior descending - LAD or circumflex artery - Cx) and compared, using the propensity score matching analysis, with 11 healthy patients. Several anatomic features were evaluated: Left main (LM) length, angle between descending coronary artery (LAD) and its first branch, angle between LAD and LM, distance from the annulus to RCA (a-RCA distance) and LM (a-LM distance) ostia and their ratio; ratio between LM length and length a-LM and tortuosity score of the vessel with SCAD. A fluid dynamic analysis has been performed to evaluate the effects on shear stress of vessels wall. RESULTS: LM length was significantly shorter in patients with SCAD versus healthy subjects (P=0.01) as well as LM length/a-LM (P=0.03) and the angle between LAD and the first adjacent branch was sharper (P<0.01). Tortuosity score showed a statistically significant difference between groups (P<0.001). Fluid dynamic analysis demonstrates that, in SCAD group, an angle<90 degree is present at the first bifurcation and it can be a cause of increased strain on vessel wall in patients with high tortuosity of coronary artery. CONCLUSION: Tortuosity and angle between the LAD and the adjacent arterial branch combined may determine increased shear stress on the vessel wall that increases the risk of SCAD.

Effect of bovine viral diarrhea virus on subsequent infectivity of bovine gammaherpesvirus 4 in endometrial cells in primary culture: An in vitro model of viral co-infection.

Bovine viral diarrhea virus (BVDV) and bovine gammaherpesvirus 4 (BoHV-4) infect the uterus of cattle, being responsible for huge economic losses. Most of the pathogenesis of BoHV-4 in the bovine reproductive tract has been elucidated by conducting tests on primary cultures. Thus, it is important to have optimal in vitro conditions, avoiding the presence of other pathogens that can alter the results. BVDV is one of the most frequent viral contaminants of cell cultures. Considering that non-cytopathic (NCP) BVDV biotype can generate persistently infected (PI) cattle, which are the major source for virus transmission in susceptible herds, it is important to check products derived from cattle that are intended to be used in research laboratories. The aim of this work was to evaluate how the natural infection of bovine endometrial cells (BEC) with a NCP BVDV strain (BEC + BVDV) affects BoHV-4 replication. We have demonstrated a delay in BoHV-4 gene expression and a decrease in viral load in the extracellular environment in BEC + BDVD cells compared to BEC (BVDV-free) cells. These results confirm that replication of BoHV-4 in BEC primary cultures is affected by previous infection with BVDV. This finding highlights the importance of ruling out BVDV infection in bovine primary cell cultures to avoid biological interference or misinterpretation of results at the time of performing in vitro studies with BoHV-4.

Gene expression and in vitro replication of bovine gammaherpesvirus type 4.

In vitro cell cultures are widely used models for dissecting cellular and molecular mechanisms that lead to certain physiological conditions and diseases. The pathogenesis of BoHV-4 in the bovine reproductive tract has been studied by conducting tests on primary cultures. However, many questions remain to be answered about the role of BoHV-4 in endometrial cells. The aim of this study was to compare the replication and gene expression of BoHV-4 in cell lines and bovine reproductive tract primary cells as an in vitro model for the study of this virus. We demonstrated that BoHV-4 strains differ in their in vitro growth kinetics and gene expression but have the same cell type preference. Our results demonstrate that BoHV-4 replicates preferentially in bovine endometrial cells (BEC). However, its replication capacity extends to various cell types, since all cells that were tested were permissive to BoHV-4 infection. The highest virus titers were obtained in BEC cells. Nevertheless, virus replication efficiency could not be fully predicted from the mRNA expression profiles. This implies that there are multiple cell-type-dependent factors and strain properties that determine the level of BoHV-4 replication. The results of this study provide relevant information about the in vitro behavior of two field isolates of BoHV-4 in different cell cultures. These findings may be useful for the design of future in vitro experiments to obtain reliable results not only about the pathogenic role of BoHV-4 in the bovine female reproductive tract but also in the development of efficient antiviral strategies.

Memory effects and self-excited oscillations in deterministic epidemic models with intrinsic time delays.

The simplest delay differential equation describing the dynamics of non-lethal infectious diseases in a fixed-size population is extended to include the incubation period, as an additional delay parameter. It is observed that these types of deterministic models consist of one delay differential equation, whereas standard SIR and SEIR models consist of two and three ordinary differential equations, respectively. The extended model presents interesting peculiarities as, for example, initial oscillatory patterns in the curve counting the infectious individuals. A comparison of the doubly delayed differential equation with the standard SEIR model is made. It is argued that self-sustained oscillations, which are intrinsic properties of models with time delay, have to be taken into account in designing optimal epidemic containment strategies.

Pancreaticoduodenectomy for paraduodenal pancreatitis is associated with a higher incidence of diabetes but a similar quality of life and pain control when compared to medical treatment.

BACKGROUND: Paraduodenal pancreatitis is a focal form of chronic pancreatitis that affects the groove area between the duodenum and the head of the pancreas. Consensus regarding surgical or nonsurgical management as the best treatment option is still lacking. METHODS: We retrospectively evaluated all patients managed for PP at The Pancreas Institute of the University Hospital Trust of Verona from 1990 to 2017. The outcomes of surgical vs. medical treatment with regard to pain control, quality of life and pancreatic insufficiency were evaluated through specific questionnaires. RESULTS: The final study population consisted of 75 patients: 62.6% underwent surgery, and 37.4% were managed without surgery. All surgical procedures consisted of pancreaticoduodenectomy. The median follow-up from the diagnosis of paraduodenal pancreatitis was 60 (12-240) months. Patients who underwent surgery experienced a similar incidence of steatorrhea (44.7 vs. 52.6%; p = 0.4) but a significantly higher incidence of diabetes (59.6 vs. 10.7%; p < 0.01) when compared to those managed without surgery. There was no difference in terms of reported chronic pain (Graded Chronic Pain Scale, median 0 vs. 1; p = 0.1) and quality of life (Pancreatitis QoL Instrument, median 82 vs. 79; p = 0.2). However, surgical patients reported a worse level of self-care activities associated with glycemic control (Diabetes Self-Management Questionnaire, median 20 vs. 28, p = 0.02). CONCLUSION: In patients affected by paraduodenal pancreatitis, surgery and medical therapy seem to obtain similar results in terms of quality of life and pain control. However, surgery is associated with an increased prevalence of postoperative diabetes with consequent relevant issues with self-care management. Surgery should be considered only in selected patients after adequate medical treatment.

The Von Willebrand Factor Antigen Plasma Concentration: a Monitoring Marker in the Treatment of Aortic and Mitral Valve Diseases.

Von Willebrand disease is a commonly inherited bleeding disorder caused by defects of von Willebrand factor (vWF). In the most common valve diseases, aortic valve stenosis (AVS) and mitral valve regurgitation (MVR), a bleeding tendency has been described in a number of patients. This has been associated to a high turbulence of blood flow through the compromised valve, promoting degradation of vWF with loss of high-molecular-weight multimers of vWF (HMWM), leading to an acquired von Willebrand syndrome (AvWS). We analysed three groups of patients, one affected by AVS, treated with transcatheter aortic valve implantation (TAVI), the second group of patients affected by MVR, treated with Mitraclip® mitral valve repair. The third group was represented by patients also affected by AVS, but not eligible for TAVI and treated with standard surgery. A fourth group of patients that underwent percutaneous coronary intervention (PCI) with stenting was used as a control. Our results demonstrated that the level of vWF measured as antigen concentration (vWF:Ag) increases in all cohorts of patients after treatment, while in control PCI patients, no modification of vWF:Ag has been registered. Western blot analysis showed only a quantitative loss of vWF in the pre-treatment time, but without significant HMWM modification. The monitoring of the vWF:Ag concentration, but not the quality of HMWM, can indicate the status of blood flow in the treated patients, thus introducing the possibility of using the vWF antigen detection in monitoring the status of replaced or repaired valves.

Effectiveness of the new generation transcatheter aortic valve in the real life studies. Review and meta-analysis.

OBJECTIVE: The aim of the meta-analysis was to assess post-procedural outcome of the new generation of transcatheter aortic valve implantation (TAVI) devices, focusing on the transfemoral and balloon-expandable SAPIEN 3 (Edwards Lifesciences Inc., Irvine, CA, USA), the self-expanding CoreValveTM Evolut series R and PRO (R/PRO)TM (Medtronic Inc., Minneapolis, MN, USA) and ACURATE neoTM transcatheter aortic valve (Symetis SA, a Boston Scientific company, Ecublens, Switzerland). MATERIALS AND METHODS: All observational studies were retrieved through PubMed computerized database from January 2014 until June 30th, 2019. The risk difference (RD) with the 95% confidence interval (CI) was used to assess the effectiveness of the intervention under comparison. The primary end point was 30-day mortality. Safety end points included: (i) stroke, (ii) moderate/severe paravalvular leak, and (iii) the need for new permanent pacemaker implantation. RESULTS: Meta-analysis demonstrated no significant differences as regards to either 30-day mortality or stroke for all the groups of prostheses under comparison. ACURATE neo was associated with significantly less new permanent pacemaker implantation compared to SAPIEN 3 (RD: -0.06; 95% CI -0.08 to -0.03; p<0.0001; I2=0%) or to EVOLUT R/PRO (RD: -0.06; 95% CI -0.09 to -0.02; p=0.0009; I2=0%). A significant reduction of new permanent pacemaker need was observed in the group of patients implanted with SAPIEN 3 compared to EVOLUT R/PRO (RD: -0.07; 95% CI -0.09 to -0.04; p<0.00001; I2=7%). The occurrence of moderate/severe leak was significantly increased in the group of patients implanted with ACURATE neo vs. SAPIEN 3 (RD: 0.04; 95% CI 0.02 to 0.05; p<0.00001; I2=0%). No significant differences were found between ACURATE neo vs. EVOLUT R/PRO (RD: -0.01; 95% CI -0.04 to 0.02; p=0.69; I2=0%) and between SAPIEN 3 vs. EVOLUT R/PRO (RD: -0.01; 95% CI -0.04 to 0.01; p=0.28; I2=73%). CONCLUSIONS: The results of the meta-analysis show that: (1) ACURATE neo was associated with significantly less new permanent pacemaker implantation than SAPIEN 3 and EVOLUT R/PRO; (2) SAPIEN 3 had significantly lower occurrence of moderate/severe valvular leak than ACURATE neo.

Meta-analysis of the impact on early and late mortality of TAVI compared to surgical aortic valve replacement in high and low-intermediate surgical risk patients.

OBJECTIVE: We studied the impact of transcatheter aortic valve implantation (TAVI) compared to the surgical aortic valve replacement (SAVR) on 30-day and one-year mortality from randomized controlled trials (RCTs) in patients with severe aortic stenosis at high or low-intermediate surgical risk. MATERIALS AND METHODS: All RCTs were retrieved through PubMed computerized database and the site https://www.clinicaltrials.gov from January 2010 until March 31st, 2019. The absolute risk reduction (RD) with the 95% confidence interval (CI) was used to assess the effectiveness of the intervention under comparison. We evaluated overall mortality rates at 30-day and one-year follow-up in the comparison between TAVI vs. SAVR. We also evaluated the role played by the site access for TAVI performed through the femoral or subclavian artery (TV-TAVI) vs. SAVR, or transapically (TA-TAVI) vs. SAVR. RESULTS: In the "as-treated population" the overall 30-day mortality was significantly lower in TAVI (p=0.03) with respect to SAVR. However, the analysis for TAVI subgroups showed that 30-day mortality was (1) significantly lower in TV-TAVI vs. SAVR (p=0.006), (2) increased, not significantly, in TA-TAVI vs. SAVR (p=0.62). No significant differences were found between TAVI vs. SAVR at one-year follow-up. CONCLUSIONS: The results of our meta-analysis suggest that TV-TAVI is a powerful tool in the treatment of severe aortic stenosis at high or low-intermediate surgical risk, with a significant lower mortality with respect to SAVR. On the contrary, SAVR seems to provide better results than TA-TAVI.

Efficacy and safety of dronedarone in patients with amiodarone-induced hyperthyroidism: a clinical study.

OBJECTIVE: The aim of the study was to examine the safety and efficacy of dronedarone in patients with a history of atrial fibrillation and amiodarone-induced hyperthyroidism. PATIENTS AND METHODS: We conducted a prospective study to evaluate the use of amiodarone and dronedarone in 124 patients with a history of paroxysmal atrial fibrillation who had no additional structural heart disease. All patients received amiodarone 200 mg qd. Out of 124 patients, 56 (45%) switched to dronedarone 400 mg bid due to amiodarone-induced hyperthyroidism and the remaining 68 patients (55%), with normal thyroid function, continued to receive amiodarone. The follow-up period was 12 months, and the patients were regularly monitored. RESULTS: The primary outcome after 6 months dronedarone and amiodarone group was 56 and 68, including 38 (68%) and 54 (79.4%) (Odds ratio [OR] = 1.17, 95% confidence interval [95% CI] = 0.68-2.02) patients with sinus rhythm (SR) and 18 (32.14%) and 14 (28.6%) (odds ratio [OR] = 0.64, confidence interval [95% CI] = 0.29-1.40) patients with atrial fibrillation (AF). The secondary outcome after 12 months showed significant difference in thyroid function in the dronedarone group. Out of 46 patients, 24 (56.18%) patients reduced hyperthyroidism compared to the amiodarone group; out of 68, 6 (8.9%) patients were observed to have hyperthyroidism. At 12 months, there were 24 (43%) and 22 (62%) (odds ratio [OR] = 0.75, confidence interval [95% CI] = 0.38-1.49) patients with SR, and 32 (57%) and 26 (38%) (odds ratio [OR] = 0.67, confidence interval [95% CI] = 0.36-1.25) patients with AF. CONCLUSIONS: In our study, dronedarone appears to be a good therapeutic option in the treatment of atrial fibrillation in patients with amiodarone-induced hyperthyroidism. However, long-term studies are needed to estimate the efficacy and toxicity of both drugs.

Acute Kidney Injury After Cardiac Transplantation: Foe or Common Innocent Bystander?

BACKGROUND: Heart transplantation (HT) is regarded as the treatment of choice for end-stage heart failure (ESHF) patients. Severe acute kidney injury (AKI) after HT is a frequent clinical problem with devastating consequences for HT recipients. METHODS: Data from 112 ESHF patients undergoing HT in 2010-2015 were retrospectively reviewed. The primary end point was the development of AKI stage III, and secondary outcomes were in-hospital and 1-year mortality according to Kidney Disease Improving Global Outcomes criteria. RESULTS: In total, 81 patients (72.3%) developed AKI, of which 33 (29.4%) developed AKI stage I, 18 (16%) stage II, and 30 (26.7%) stage III; within this group, 27 recipients (24%) required renal replacement therapy (RRT). Overall hospital mortality was 14%. However, when stratifying by AKI stage, hospital mortality increased from 0% to 46% comparing recipients without AKI and those with AKI stage III, respectively (P = .001). In the same way, 1-year mortality increased from 6% to 53% for recipients without AKI compared with those who developed AKI stage III (log-rank test for trend: P = .001). Recipients that required RRT had a 1-year mortality of 59.2% compared with 5.8% in those without RRT requirement. CONCLUSIONS: The findings indicate that AKI stage III is common after HT and adversely affects early and late mortality. Clinical variables together with perioperative hemodynamic assessment could add more powerful prognostic information to predict severe AKI before HT and therefore evaluate potential heart-kidney recipients.

Meta-analyses on intra-aortic balloon pump in cardiogenic shock complicating acute myocardial infarction may provide biased results.

OBJECTIVE: Intra-aortic balloon pump (IABP) is the device most commonly investigated in patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI). Recently meta-analyses on this topic showed opposite results: some complied with the actual guideline recommendations, while others did not, due to the presence of bias. We investigated the reasons for the discrepancy among meta-analyses and strategies employed to avoid the potential source of bias. MATERIALS AND METHODS: Scientific databases were searched for meta-analyses of IABP support in AMI complicated by CS. The presence of clinical diversity, methodological diversity and statistical heterogeneity were analyzed. When we found clinical or methodological diversity, we reanalyzed the data by comparing the patients selected for homogeneous groups. When the fixed effect model was employed despite the presence of statistical heterogeneity, the meta-analysis was repeated adopting the random effect model, with the same estimator used in the original meta-analysis. RESULTS: Twelve meta-analysis were selected. Six meta-analyses of randomized controlled trials (RCTs) were inconclusive because underpowered to detect the IABP effect. Five included RCTs and observational studies (Obs) and one only Obs. Some meta-analyses on RCTs and Obs had biased results due to presence of clinical and/or methodological diversity. The reanalysis of data reallocated for homogeneous groups was no more in contrast with guidelines recommendations. CONCLUSIONS: Meta-analyses performed without controlling for clinical and/or methodological diversity, represent a confounding message against a good clinical practice. The reanalysis of data demonstrates the validity of the current guidelines recommendations in addressing clinical decision making in providing IABP support in AMI complicated by CS.

Expression of oestrogen receptors (GPER, ESR1, ESR2) in human ductuli efferentes and proximal epididymis.

Oestrogen targeting in the human genital ducts is still not well-known. In fact, to date, the localization of oestrogen receptors, ESR1 and ESR2, is controversial and the presence of the membrane oestrogen receptor GPER (G protein-coupled oestrogen receptor) is unexplored. This study has investigated the expression of GPER, ESR1, ESR2 in human ductuli efferentes and proximal caput epididymis by immunohistochemistry and Western blot analysis. Furthermore, the presence of PELP1 (proline-glutamic acid-leucine-rich protein 1), a co-regulator of the oestrogen receptors, was also evaluated. In ductuli efferentes, GPER and ESR1 were clearly localized in all epithelial cells, while ESR2 was evidenced only in ciliated cells. Conversely, the epithelial cells of proximal caput epididymis revealed moderate GPER immunoreactivity, the absence of ERS1 and the occasional presence of ESR2. Furthermore, PELP1 was observed in ciliated cells of ductuli efferentes and in principal cells of proximal caput epididymis. Therefore, this study firstly demonstrated the expression of GPER in human male genital ducts, revealing a new mediator of oestrogen action in these anatomical sites. ESR1 and ESR2 were differentially localized in the two genital tracts together with PELP1, but cell sites of ERs and their co-regulator were not homogeneous. So, a different regional/cellular association of GPER with the classical oestrogen receptors was highlighted, suggesting that oestrogen action could be mediated by GPER, ESR1, ESR2 in ductuli efferentes, while by GPER and, occasionally by ESR2, in proximal caput epididymis. This study suggests that the specific oestrogen-mediated functions in human genital ducts might result from the different local interactions of oestrogens with oestrogen receptors and their co-regulators.