Cardiology of the future: xenotransplantation with porcine heart

The reduced availability of human donor hearts compared with the needs of patients with advanced heart failure refractory to medical therapy has promoted the search for therapeutic alternatives to cardiac allografts. Porcine heart xenotransplantation represents one of the most promising frontiers in this field today. From the first researches in the 1960s to today, the numerous advances achieved in the field of surgical techniques, genetic engineering and immunosuppression have made it possible at the beginning of 2022 to carry out the first swine-to-human heart transplant, attaining a survival of 2 months after surgery. The main intellectual and experimental stages that have marked the history of xenotransplantation, the latest acquisitions in terms of genetic editing, as well as the improvement of immunosuppressive therapy are discussed analytically in this article in order to illustrate the underlying complexity of this therapeutic model

Clinical and Prognostic Implications of Right Ventricular Uptake on Bone Scintigraphy in Transthyretin Amyloid Cardiomyopathy

Background: The extent of myocardial bone tracer uptake with technetium pyrophosphate, hydroxymethylene diphosphonate, and 3,3-diphosphono-1,2-propanodicarboxylate in transthyretin amyloid cardiomyopathy (ATTR-CM) might reflect cardiac amyloid burden and be associated with outcome. Methods: Consecutive patients with ATTR-CM who underwent diagnostic bone tracer scintigraphy with acquisition of whole-body planar and cardiac single-photon emission computed tomography (SPECT) images from the National Amyloidosis Centre and 4 Italian centers were included. Cardiac uptake was defined according to the Perugini classification: 0=absent cardiac uptake; 1=mild uptake less than bone; 2=moderate uptake equal to bone; and 3=high uptake greater than bone. Extent of right ventricular (RV) uptake was defined as focal (basal segment of the RV free wall only) or diffuse (extending beyond basal segment) on the basis of SPECT imaging. The primary outcome was all-cause mortality. Results: Among 1422 patients with ATTR-CM, RV uptake accompanying left ventricular uptake was identified by SPECT imaging in 100% of cases at diagnosis. Median follow-up in the whole cohort was 34 months (interquartile range, 21 to 50 months), and 494 patients died. By Kaplan-Meier analysis, diffuse RV uptake on SPECT imaging (n=936) was associated with higher all-cause mortality compared with focal (n=486) RV uptake (77.9% versus 22.1%; P<0.001), whereas Perugini grade was not associated with survival (P=0.27 in grade 2 versus grade 3). On multivariable analysis, after adjustment for age at diagnosis (hazard ratio [HR], 1.03 [95% CI, 1.02-1.04]; P<0.001), presence of the p.(V142I) TTR variant (HR, 1.42 [95% CI, 1.20-1.81]; P=0.004), National Amyloidosis Centre stage (each category, P<0.001), stroke volume index (HR, 0.99 [95% CI, 0.97-0.99]; P=0.043), E/e' (HR, 1.02 [95% CI, 1.007-1.03]; P=0.004), right atrial area index (HR, 1.05 [95% CI, 1.02-1.08]; P=0.001), and left ventricular global longitudinal strain (HR, 1.06 [95% CI, 1.03-1.09]; P<0.001), diffuse RV uptake on SPECT imaging (HR, 1.60 [95% CI, 1.26-2.04]; P<0.001) remained an independent predictor of all-cause mortality. The prognostic value of diffuse RV uptake was maintained across each National Amyloidosis Centre stage and in both wild-type and hereditary ATTR-CM (P<0.001 and P=0.02, respectively). Conclusions: Diffuse RV uptake of bone tracer on SPECT imaging is associated with poor outcomes in patients with ATTR-CM and is an independent prognostic marker at diagnosis

Clinical and Prognostic Implications of Right Ventricular Uptake on Bone Scintigraphy in Transthyretin Amyloid Cardiomyopathy

BACKGROUND: The extent of myocardial bone tracer uptake with technetium pyrophosphate, hydroxymethylene diphosphonate, and 3,3-diphosphono-1,2-propanodicarboxylate in transthyretin amyloid cardiomyopathy (ATTR-CM) might reflect cardiac amyloid burden and be associated with outcome. METHODS: Consecutive patients with ATTR-CM who underwent diagnostic bone tracer scintigraphy with acquisition of whole-body planar and cardiac single-photon emission computed tomography (SPECT) images from the National Amyloidosis Centre and 4 Italian centers were included. Cardiac uptake was defined according to the Perugini classification: 0=absent cardiac uptake; 1=mild uptake less than bone; 2=moderate uptake equal to bone; and 3=high uptake greater than bone. Extent of right ventricular (RV) uptake was defined as focal (basal segment of the RV free wall only) or diffuse (extending beyond basal segment) on the basis of SPECT imaging. The primary outcome was all-cause mortality. RESULTS: Among 1422 patients with ATTR-CM, RV uptake accompanying left ventricular uptake was identified by SPECT imaging in 100% of cases at diagnosis. Median follow-up in the whole cohort was 34 months (interquartile range, 21 to 50 months), and 494 patients died. By Kaplan-Meier analysis, diffuse RV uptake on SPECT imaging (n=936) was associated with higher all-cause mortality compared with focal (n=486) RV uptake (77.9% versus 22.1%; P<0.001), whereas Perugini grade was not associated with survival (P=0.27 in grade 2 versus grade 3). On multivariable analysis, after adjustment for age at diagnosis (hazard ratio [HR], 1.03 [95% CI, 1.02-1.04]; P<0.001), presence of the p.(V142I) TTR variant (HR, 1.42 [95% CI, 1.20-1.81]; P=0.004), National Amyloidosis Centre stage (each category, P<0.001), stroke volume index (HR, 0.99 [95% CI, 0.97-0.99]; P=0.043), E/e' (HR, 1.02 [95% CI, 1.007-1.03]; P=0.004), right atrial area index (HR, 1.05 [95% CI, 1.02-1.08]; P=0.001), and left ventricular global longitudinal strain (HR, 1.06 [95% CI, 1.03-1.09]; P<0.001), diffuse RV uptake on SPECT imaging (HR, 1.60 [95% CI, 1.26-2.04]; P<0.001) remained an independent predictor of all-cause mortality. The prognostic value of diffuse RV uptake was maintained across each National Amyloidosis Centre stage and in both wild-type and hereditary ATTR-CM (P<0.001 and P=0.02, respectively). CONCLUSIONS: Diffuse RV uptake of bone tracer on SPECT imaging is associated with poor outcomes in patients with ATTR-CM and is an independent prognostic marker at diagnosis

The Effect of Adjuvant Radiotherapy on One- and Two-Stage Prosthetic Breast Reconstruction and on Autologous Reconstruction: A Multicenter Italian Study among 18 Senonetwork Breast Centres

Purpose: In modern breast cancer treatment, a growing role has been observed for breast reconstruction together with an increase in clinical indications for postmastectomy radiotherapy (PMRT). Choosing the optimum type of reconstructive technique is a clinical challenge. We therefore conducted a national multicenter study to analyze the impact of PMRT on breast reconstruction. Methods: We conducted a retrospective case-control multicenter study on women undergoing breast reconstruction. Data were collected from 18 Italian Breast Centres and stored in a cumulative database which included the following: autologous reconstruction, direct-to-implant (DTI), and tissue expander/immediate (TE/I). For all patients, we described complications and surgical endpoints to complications such as reconstruction failure, explant, change in type of reconstruction, and reintervention. Results: From 2001 to April 2020, 3116 patients were evaluated. The risk for any complication was significantly increased in patients receiving PMRT (aOR, 1.73; 95% CI, 1.33-2.24; p < 0.001). PMRT was associated with a significant increase in the risk of capsular contracture in the DTI and TE/I groups (aOR, 2.24; 95% CI, 1.57-3.20; p < 0.001). Comparing type of procedures, the risk of failure (aOR, 1.82; 95% CI, 1.06-3.12, p=0.030), explant (aOR, 3.34; 95% CI, 3.85-7.83, p < 0.001), and severe complications (aOR, 2.54; 95% CI, 1.88-3.43, p < 0.001) were significantly higher in the group undergoing DTI reconstruction as compared to TE/I reconstruction. Conclusion: Our study confirms that autologous reconstruction is the procedure least impacted by PMRT, while DTI appears to be the most impacted by PMRT, when compared with TE/I which shows a lower rate of explant and reconstruction failure. The trial is registered with NCT04783818, and the date of registration is 1 March, 2021, retrospectively registered

Prognostic significance of unexplained left ventricular hypertrophy in patients undergoing carpal tunnel surgery

12Carpal tunnel (CT) syndrome is a recognized red-flag of cardiac amyloidosis (CA) and increased cardiovascular (CV) morbidity. We designed this study to characterize the CV profile of patients with CT syndrome at the time of first surgery and to identify high-risk presentations.openopenPorcari, Aldostefano; Pagura, Linda; Longo, Francesca; Sfriso, Enrico; Barbati, Giulia; Murena, Luigi; Longo, Emiliano; Ramella, Vittorio; Arnež, Zoran Marij; Rapezzi, Claudio; Merlo, Marco; Sinagra, GianfrancoPorcari, Aldostefano; Pagura, Linda; Longo, Francesca; Sfriso, Enrico; Barbati, Giulia; Murena, Luigi; Longo, Emiliano; Ramella, Vittorio; Arnež, Zoran Marij; Rapezzi, Claudio; Merlo, Marco; Sinagra, Gianfranc

Acute appendicitis: what is the gold standard of treatment?

cBurney's procedure represented the gold-standard for acute appendicitis until 1981, but nowadays the number of laparoscopic appendectomies has progressively increased since it has been demonstrated to be a safe procedure, with excellent cosmetic results and it also allows a shorter hospitalization, a quicker and less painful postoperative recovery. The aim of this editorial was to perform a review of the literature in order to address controversial issues in the treatment of acute appendicitis

Prognostic value of echocardiographic evaluation of cardiac mechanics in patients with aortic stenosis and preserved left ventricular ejection fraction

Left ventricular ejection function (LVEF) is not reliable in identifying subtle systolic dysfunction. Speckle Tracking (ST) plays a promising role and hemodynamic forces (HDFs) are emerging as marker of LV function. The role of LV myocardial deformation and HDFs was investigated in a cohort of patients with aortic stenosis (AS) and normal LVEF. Two hundred fifty three patients (median age 79 years, IQR 73 - 83 years) with mild (n = 87), moderate (n =77) and severe AS (n =89) were retrospectively enrolled. 2D echocardiographic global longitudinal strain (GLS), circumferential strain (GCS) and HDFs were determined. The worsening of AS was associated with raising inappropriate LV mass (p -19,9%) and LV systolic longitudinal force (LVsysLF) value (< 12,49), patients with impaired ST and lower HDFs components had increased incidence of aortic valve replacement (AVR) and worse survival (p <0.024 and p <0.037, respectively). Among ST and HDFs parameters, only LVsysLF was independently associated with AVR and all causes mortality on multivariable Cox regression analysis (HR 0.94; 95% CI 0.89-0.99; p= 0.012). Reduced values of LVsysLF were associated with AVR and reduced survival in AS patients. LVsysLF could provide useful information in the stratification of patients with AS and possibly in the choice of timing for AVR

The effects of acupuncture after thyroid surgery: A randomized, controlled trial.

Background. Acupuncture is a safe and well-tolerated treatment for pain relief Previous studies supported the effectiveness of several acupuncture techniques for postoperative pain. The aim of this randomized, controlled trial was to evaluate the efficacy of acupuncture in reducing pain after thyroid surgery. Methods. We randomized 121 patients to a control group (undergoing only standard postoperative analgesic treatment with acetaminophen) and an acupuncture group, undergoing also either electroacupuncture (EA) or traditional acupuncture (TA). Pain was measured according to intra-operative remifentanil use, acetaminophen daily intake, Numeric Rating Scale (NRS), and McGill Pain Questionnaire on postoperative days (POD) 1-3. Results. Acupuncture group required less acetaminophen than controls at POD 2 (P = .01) and 3 (P = .016). EA patients required less remifentanil (P = .032) and acetaminophen than controls at POD 2 (P = .004) and 3 (P = .008). EA patients showed a trend toward better NRS and McGill scores from POD 1 to 3 compared with controls. EA patients had a lower remifentanil requirement and better NRS and McGill scores than TA patients. No differences occurred between TA patients and controls. Conclusion. Acupuncture may be effective in reducing pain after thyroid surgery. EA is more useful; TA achieves no significant effects

Prognostic Role of the Progression of Late Gadolinium Enhancement in Hypertrophic Cardiomyopathy

In hypertrophic cardiomyopathy (HCM), Late Gadolinium Enhancement (LGE) extent ≥15% of left ventricular (LV) mass is considered a prognostic risk factor. LGE extent increases over time and the clinical role of the progression of LGE over time (LGE-rate) was not prospectively evaluated. We sought to evaluate the prognostic role of LGE-rate in HCM. We enrolled 105 patients with HCM who underwent cardiac-MR at baseline (CMR-I) and after ≥2 years of follow-up (CMR-II). LGE-rate was defined as the ratio between the increase of LGE extent (g) and the time interval (months) between examinations. A combined endpoint of sudden cardiac death, resuscitated cardiac arrest, appropriate ICD intervention and sustained VT was used (hard events). The percentage of patients with LGE extent ≥15% increased from 9% to 20% from CMR-I to CMR-II (p=0.03). During a median follow-up of 52 months, 25 hard events were recorded. The presence of LGE≥15% at CMR-II allowed a significant reclassification of the risk of patients than at LGE≥15% at CMR-I (NRI 0.21, p=0.046). At MaxStat analysis the optimal prognostic cut-point for LGE-rate was &gt;0.07 g/months. At Kaplan-Meier curve patients with LGE-rate&gt;0.07 had worse prognosis than those without (p&lt;0.0001). LGE-rate&gt;0.07 allowed a significant reclassification of the risk compared to LGE≥15% at CMR-I and at CMR-II (NRI 0.49, p=0.003). In multivariable models, LGE-rate&gt;0.07 was the best independent predictor of hard events. In conclusion, CMR should be repeated after 2 years to reclassify the risk sudden death of those patients. High LGE-rate may be considered a novel prognostic factor in HCM

Colorectal polypoid lesions and expression of vascular endothelial growth factor in a consecutive series of endoscopic and surgical patients

Colorectal cancer incidence in patients undergoing screening protocols is decreasing because of the higher rate of discovered preneoplastic colonic lesions; however, adenomatous polyps may not always be removable endoscopically and surgery may still be necessary. The aim of this study was to assess the vascular endothelial growth factor expression in the different steps of colorectal carcinogenesis to explore its potential role as a marker of malignancy in polypoid lesions. A total of 92 subjects with colonic adenoma or cancer who underwent screening colonoscopy or surgery were prospectively enrolled. Real-time reverse transcription polymerase chain reaction for VEGF-A messenger RNA expression and immunohistochemistry for VEGF-A were performed. Immunoassays for VEGF-A, VEGF-C, VEGFR-1, VEGFR-2, and VEGFR-3 were also performed. Non-parametric statistics, receiver operating characteristic curve analysis, and logistic multiple regression analysis were used. VEGF-A messenger RNA expression was higher in patients with high-grade dysplasia or colorectal cancer than in those with low-grade dysplasia adenomas (p = 0.01). At immunohistochemistry, VEGF-A expression was significantly higher in colorectal cancer patients compared to dysplastic adenomas (p &lt; 0.001), and the accuracy of VEGF-A expression for prediction of malignancy was 91.7 (95% confidence interval = 78.7-97.9). VEGF-C protein expression was lower in colorectal cancer patients than in simple adenomas (p = 0.02). VEGF-A levels were directly correlated to polyp size (rho = 0.73, p = 0.0062). Multivariate analysis demonstrated that malignancy and polyp size were independent predictors of VEGF-A mucosal levels. This study demonstrated that the VEGF-A expression changes along the colorectal carcinogenesis pathway showing a neat step up at the passage from high-grade dysplasia to invasive cancer. This feature might potentially be useful to stratify colorectal polyps in different risks of progression classes. Moreover, the high level of VEGF-A expression predicted the presence of lymphovascular invasion with good accurac