[Preventive myocardial revascularization prior to abdominal aortic repair in patients without cardiac symptoms: long-term results]. / Profilakticheskaya revaskulyarizatsiya miokarda pered rezektsiei anevrizmy bryushnoi aorty u kardiologicheski asimptomnykh bol'nykh: otdalennye rezul'taty.

OBJECTIVE: To evaluate the long-term influence of preoperative invasive coronary screening and preventive myocardial revascularization on mortality and cardiac complications after open surgery for abdominal aortic aneurysms (AAA). MATERIAL AND METHODS: We present long-term outcomes after open surgery for AAA between 2011 and 2022. Patients without clinical or objective signs of coronary artery disease were included. In the 1st group, routine coronary angiography was performed before surgery. Prophylactic myocardial revascularization was performed in 12 cases. Long-term data on 45 patients were obtained. In the 2nd group, 53 patients underwent repair without invasive coronary screening, and data on 48 patients were obtained in this group. RESULTS: The median follow-up was 32 and 79 months, respectively. Kaplan-Meyer overall 48-month survival was 87.3% and 82.1%, respectively (p=0.278). In the first group, 2 patients developed angina pectoris in the same period. In the second group, we observed 2 cases of myocardial infarction and 3 cases of angina pectoris without infarction. Analysis of survival curves found no significant differences (p=0.165). CONCLUSION: In our study, invasive coronary screening and preventive myocardial revascularization in patients without clinical and objective signs of coronary artery did not improve 4-year long-term period after abdominal aortic repair. Perhaps, differences will appear after 4 years, and this requires further follow-up after coronary angiography. However, there is a tendency towards more common onsets of coronary artery disease that dictates the need for cardiac monitoring of such patients.

[Fifteen-year results of bilateral and unilateral internal mammary artery grafting]. / Pyatnadtsatiletnie rezul'taty revaskulyarizatsii miokarda s ispol'zovaniem dvukh i odnoi vnutrennei grudnoi arterii.

OBJECTIVE: To evaluate the clinical effectiveness of bilateral internal mammary artery grafting over long-term (15 years) postoperative period. MATERIAL AND METHODS: There were 276 patients divided into two groups: 135 patients (group A) underwent bilateral internal mammary artery grafting and 141 patients (group B) underwent unilateral internal mammary artery grafting together with venous bypass grafts. On-pump surgeries and cardioplegia, parallel CPB and on-pump procedures were performed in equal proportions. Mean age of patients was 57.3±7.6 years. Diabetes mellitus was detected in 21 (15.5%) and 24 (19.1%) patients, respectively (p>0.05). Mean LV ejection fraction was 55.4±9.9%, revascularization index - 3.1±0.8 and 3.0±0.7, respectively. In the 1st group, 43 patients underwent bilateral internal mammary artery grafting alone. Autovenous grafts were additionally used in other 84 patients. RESULTS: Ten-year survival exceeded 90% in both groups. Freedom from adverse cardiac events after 15 years was significantly higher in group A (77.3% vs. 59.3%, p=0.018). In group A, 16 patients died throughout this period due to cancer (50%), myocardial infarction (12.5%), stroke (18.8%) and complications of diabetes mellitus (6.3%). In group B, 22 patients died mainly from cardiac causes (myocardial infarction - 40.9%, cancer - 27.3%). CONCLUSION: Bilateral internal mammary artery grafting has obvious advantages over traditional coronary artery bypass grafting. If we take into account higher proportion of cardiac causes in structure of mortality in group B, we can talk about positive impact of bilateral internal mammary artery grafting not only on the quality of life, but also on life expectancy in long-term postoperative period.

Long-term Outcomes of Adults With Tricuspid Regurgitation Following Transcatheter Atrial Septal Defect Closure.

BACKGROUND: Functional tricuspid regurgitation (TR) is a common pathophysiologic condition in adults with ostium secundum atrial septal defect (ASD). The aim of this study was to evaluate long-term outcomes following transcatheter ASD closure, which have not been well studied among patients with significant TR. METHODS: We reviewed consecutive adult patients who underwent transcatheter ASD closure at Toronto General Hospital, Ontario, Canada, from 1998 to 2016. We linked our hospital registry with Ontario population-based health administrative databases to collect longitudinal data on inpatient and outpatient health care utilisation and vital status. RESULTS: In this cohort study of 949 patients, 199 (22%) had moderate to severe TR before transcatheter ASD closure. A significant proportion of patients (61%) showed improvement in TR severity to at least mild TR after ASD intervention. At a median follow-up of 10.9 years, patients with baseline mild or no TR, compared with those with greater than moderate TR, had significantly lower rates of all-cause mortality (6.8 vs 22.5 per 1000 person-years [PY]; P < 0.001), composite hospitalisation for atrial fibrillation (AF) or heart failure (HF) (22.3 vs 49.1 per 1000 PY; P < 0.001), and new onset of AF (10.4 vs 20.2 per 1000 PY; P = 0.002) and HF (5.0 vs 9.2 per 1000 PY; P = 0.039). Preprocedural TR was independently associated with higher all-cause mortality (adjusted hazard ratio 1.69, 95% confidence interval 1.08-2.62). CONCLUSIONS: TR severity was independently associated with a higher risk of mortality and morbidity. Further investigation of earlier device closure or concomitant tricuspid valve intervention may be of interest.

Long-term outcomes of truncus arteriosus repair: A modulated renewal competing risks analysis.

OBJECTIVE: In this study, we sought to identify independent risk factors for mortality and reintervention after early surgical correction of truncus arteriosus using a novel statistical method. METHODS: Patients undergoing neonatal/infant truncus arteriosus repair between January 1984 and December 2018 were reviewed retrospectively. An innovative statistical strategy was applied integrating competing risks analysis with modulated renewal for time-to-event modeling. RESULTS: A total of 204 patients were included in the study. Mortality occurred in 32 patients (15%). Smaller right ventricle to pulmonary artery conduit size and truncal valve insufficiency at birth were significantly associated with overall mortality (right ventricle to pulmonary artery conduit size: hazard ratio, 1.34; 95% confidence interval, 1.08-1.66, P = .008; truncal valve insufficiency: hazard ratio, 2.5; 95% confidence interval, 1.13-5.53, P = .024). truncal valve insufficiency at birth, truncal valve intervention at index repair, and number of cusps (4 vs 3) were associated with truncal valve reoperations (truncal valve insufficiency: hazard ratio, 2.38; 95%, confidence interval, 1.13-5.01, P = .02; cusp number: hazard ratio, 6.62; 95% confidence interval, 2.54-17.3, P < .001). Right ventricle to pulmonary artery conduit size 11 mm or less was associated with a higher risk of early catheter-based reintervention (hazard ratio, 1.54; 95% confidence interval, 1.04-2.28, P = .03) and reoperation (hazard ratio, 1.96; 95% confidence interval, 1.33-2.89, P = .001) on the right ventricle to pulmonary artery conduit. CONCLUSIONS: Smaller right ventricle to pulmonary artery conduit size and truncal valve insufficiency at birth were associated with overall mortality after truncus arteriosus repair. Quadricuspid truncal valve, the presence of truncal valve insufficiency at the time of diagnosis, and truncal valve intervention at index repair were associated with an increased risk of reoperation. The size of the right ventricle to pulmonary artery conduit at index surgery is the single most important factor for early reoperation and catheter-based reintervention on the conduit.

Aortic root replacement with bicuspid valve reimplantation: Are outcomes and valve durability comparable to those of tricuspid valve reimplantation?

OBJECTIVES: To assess intermediate-term outcomes of aortic root replacement with valve-sparing reimplantation of bicuspid aortic valves (BAV), compared with tricuspid aortic valves (TAV). METHODS: From January 2002 to July 2017, 92 adults underwent aortic root replacement with BAV reimplantation and 515 with TAV reimplantation at the Cleveland Clinic. Balancing-score matching based on 28 preoperative variables yielded 71 well-matched BAV and TAV pairs (77% of possible pairs) for comparison of postoperative mortality and morbidity, longitudinal echocardiogram data, aortic valve reoperation, and survival. RESULTS: In the BAV group, 1 hospital death occurred (1.1%); mortality among all reimplantations was 0.2%. Among matched patients, procedural morbidity was low and similar between BAV and TAV groups (1 stroke in TAV group; renal failure requiring dialysis, 1 patient each; red cell transfusion, 25% each). Five-year results: Severe aortic regurgitation was present in 7.4% of the BAV group and 2.9% of the TAV group (P = .7); 39% of BAV and 65% of TAV patients had none. Higher mean gradients (10 vs 7.4 mm Hg; P = .001) and left ventricular mass index (111 vs 101 g/m2; P = .5) were present in BAV patients. Freedom from aortic valve reoperation was 94% in the BAV group and 98% in the TAV group (P = .10), and survival was 100% and 95%, respectively (P = .07). CONCLUSIONS: Both BAV and TAV reimplantations can be performed with equal safety and good midterm outcomes; however, the constellation of higher gradients, less ventricular reverse remodeling, and more aortic valve reoperations with BAV reimplantations raises concerns requiring continued long-term surveillance.

Long-term outcomes of Holmium laser enucleation of prostate and predictive model for symptom recurrence.

INTRODUCTION AND OBJECTIVES: Holmium laser enucleation of prostate (HoLEP) represents one of the most studied surgical techniques for benign prostatic hyperplasia (BPH). Its efficacy in symptom relief has been widely depicted. However, few evidence is available regarding the possible predictors of symptom recurrence. We aimed to evaluate long-term outcomes, symptom recurrence rate, and predictors in patients that underwent HoLEP. MATERIALS AND METHODS: We retrospectively analyzed data from patients that consecutively underwent HoLEP for BPH from 2012 to 2015 at two tertiary referral centers. Functional outcomes were evaluated by uroflowmetry parameters and International Prostate Symptom Score (IPSS) questionnaire administration at follow-up visits at 12, 24, and 60 months. The primary outcome was the symptomatic patients' rate presenting lower urinary tract symptoms (LUTS) after 60 months from surgery, defined as in case of one or more of the following: IPSS more than 7, post voidal residue (PVR) more than 20 ml, need for medical therapy for LUTS or redo surgery for bladder outlet obstruction. Multivariable logistic regression analyses evaluated predictors for being symptomatic at follow-up. Covariates consisted of: preoperative peak flow rate (PFR), PVR, and IPSS, prostate volume, age (all as continuous), and surgical technique. RESULTS: A total of 567 patients were available for our analyses. Median prostate volume was 80cc, with a median PFR of 8 ml/s and median PVR of 100cc. One hundred and twenty-five (22%) patients were found to be symptomatic at follow-up. Redo surgery was needed for 25 (4.4%) patients. After adjusting for possible confounders, an increase in preoperative PVR (odds ratio [OR] 1.005) and IPSS (OR 1.12) resulted as independent predictors for symptom recurrence (all p < 0.001). CONCLUSIONS: HoLEP can provide durable symptom relief regardless of the chosen technique. Patients with an important preoperative symptom burden or a high PVR should be carefully counseled on the risk of symptom recurrence.

Endoscopic Management of Low-Grade Upper Tract Urothelial Carcinoma: Characterizing the Long-term Burden of Care in Comparison to Radical Nephroureterectomy.

OBJECTIVE: To compare procedure burden, oncologic, surgical and renal-function outcomes between patients with low-grade upper urothelial cancer (UTUC) who were referred for either radical management (RM) or kidney-sparing endoscopic management (EM). PATIENTS AND METHODS: We retrospectively reviewed data of all patients treated for UTUC at our tertiary medical center between 2000 and 2018 and selected patients diagnosed with unilateral low-grade UTUC. RESULTS: Twenty-four patients were treated with EM and 37 with RM. Surgical and oncologic risk factors were similar between the arms except for tumor size. Mean follow-up was 4.9 ± 3.4 years. The 5-year overall-survival rate was 85% with EM and 84% with RM (P = .707). Metastasis-free and cancer-specific survival were also similar (P = .994, P = .960). End-of-follow-up average glomerular filtration rates were 58.7 ± 21.5 and 49.2 ± 22.1 mL/min/1.73 m2, respectively (P = .12). Ninety-two percent of patients managed endoscopically had local recurrences, with an average of 3.2 recurrences per patient. Four (17%) patients underwent salvage radical nephroureterectomy. Procedure burden was higher with EM, having 6.5 ± 4.4 operations and 344 ± 272 minutes under anesthesia compared with 1.9 ± 0.4 operations (P <.0001) and 213 ± 84 minutes under anesthesia (P = .031) with RM. Cost-of-care analysis revealed higher costs for EM in both private and publicly funded medical insurance plans. CONCLUSION: Patients undergoing endoscopic management had an 83% chance of preserving their kidney and an 81% chance of 5-year metastasis-free survival at a cost of 6.5 ± 4.4 operations during a mean follow-up of 4.9 ± 3.4 years. Our findings support EM for low-grade UTUC as a valid option from oncological aspects but highlight the associated costs.

Thyroid autoimmunity and hypothyroidism are associated with deep molecular response in patients with chronic myeloid leukemia on tyrosine kinase inhibitors.

PURPOSE: Thyroid alterations including de novo appearance of thyroid autoimmunity are adverse effects of tyrosine kinase inhibitors, used in solid and hematologic cancer therapy, but the relationship between thyroid alterations during this treatment and the outcome of chronic myeloid leukemia remains unclear. Aim of this study was to investigate whether the presence of thyroid alterations may affect the clinical outcome of chronic myeloid leukemia on tyrosine kinase inhibitors. METHODS: We evaluated thyroid function and autoimmunity in 69 chronic myeloid leukemia patients on long-term therapy looking at the association between thyroid abnormalities and disease molecular response. RESULTS: Overall, 24 of 69 (34.8%) had one or more thyroid abnormalities during therapy. A high percentage of patients (21/69, 30.4%) showed thyroid autoimmunity (positive thyroid autoantibodies with ultrasound hypoechogenicity), while clinical and subclinical hypothyroidism and subclinical hyperthyroidism were, respectively, found in 4 of 69 (5.8%) and 3 of 69 (4.3%) of cases. Second-generation tyrosine kinase inhibitors resulted significantly associated (14/32, 43.7%) with Hashimoto's thyroiditis, compared to first generation (7/37, 18.9%; p = 0.03). Interestingly, we also found a significant association between euthyroid (14/26, 53.8%) and hypothyroid Hashimoto's thyroiditis (4/26, 15.4%) in patients with deep molecular response, as compared to euthyroid (3/43, 7%; p = 0.0001) and hypothyroid (0/43, 0%; p = 0.02) Hashimoto's thyroiditis patients with major molecular response. CONCLUSIONS: Our study confirms and extends our knowledge on the tyrosine kinase inhibitors effects on thyroid, showing that thyroid autoimmunity is frequently observed in chronic myeloid leukemia patients on long-term therapy and is associated with a better oncological response.

Long-term Outcomes of Minimally Invasive Versus Open Abdominoperineal Resection for Rectal Cancer: A Single Specialized Center Experience.

BACKGROUND: Randomized studies have validated laparoscopic proctectomy for the treatment of rectal cancer as noninferior to an open proctectomy, but most of those studies have included sphincter-preserving resections along with abdominoperineal resection. OBJECTIVE: This study aimed to compare perioperative and long-term oncological outcomes between minimally invasive and open abdominoperineal resection. DESIGN: This study is a retrospective analysis of a prospectively maintained database. SETTINGS: The study was conducted in a single specialized colorectal surgery department. PATIENTS: All patients who underwent abdominoperineal resection for primary rectal cancer between 2000 and 2016 were included. MAIN OUTCOME MEASURES: The primary outcomes measured were the perioperative and long-term oncological outcomes. RESULTS: We included 452 patients, 372 in the open group and 80 in the minimally invasive group, with a median follow-up time of 74 months. There were significant differences between the groups in terms of neoadjuvant radiation treatment (67.5% of the open versus 81.3% of the minimally invasive group, p = 0.01), operative time (mean of 200 minutes versus 287 minutes, p < 0.0001), and mean length of stay (9.5 days versus 6.6 days, p < 0.0001). Overall complication rates were similar between the groups (34.5% versus 27.5%, p = 0.177). There were no significant differences in the mean number of lymph nodes harvested (21.7 versus 22.2 nodes, p = 0.7), circumferential radial margins (1.48 cm versus 1.37 cm, p = 0.4), or in the rate of involved radial margins (10.8% versus 6.3%, p = 0.37). Five-year overall survival was 70% in the open group versus 80% in the minimally invasive group (p = 0.344), whereas the 5-year disease-free survival rate in the open group was 63.2% versus 77.6% in the minimally invasive group (p = 0.09). LIMITATIONS: This study was limited because it describes a single referral institution experience. CONCLUSIONS: Although both approaches have similar perioperative outcomes, the minimally invasive approach benefits the patients with a shorter length of stay and a lower risk for surgical wound infections. Both approaches yield similar oncological technical quality in terms of the lymph nodes harvested and margins status, and they have comparable long-term oncological outcomes. See Video Abstract at http://links.lww.com/DCR/B754.RESULTADOS A LARGO PLAZO DE LA RESECCIÓN ABDOMINOPERINEAL MÍNIMAMENTE INVASIVA VERSUS ABIERTA PARA EL CÁNCER DE RECTO: EXPERIENCIA DE UN SOLO CENTRO ESPECIALIZADOANTECEDENTES:Estudios aleatorizados han validado la proctectomía laparoscópica para el tratamiento del cáncer de recto igual a la proctectomía abierta, pero la mayoría de esos estudios han incluido resecciones con preservación del esfínter junto con resección abdominoperineal.OBJETIVO:Comparar los resultados oncológicos perioperatorios y a largo plazo entre la resección abdominoperineal abierta y mínimamente invasiva.DISEÑO:Análisis retrospectivo de una base de datos mantenida de forma prospectiva.ENTORNO CLINICO:Servicio único especializado en cirugía colorrectal.PACIENTES:Todos los pacientes que se sometieron a resección abdominoperineal por cáncer de recto primario entre 2000 y 2016.PRINCIPALES MEDIDAS DE VALORACION:Resultados oncológicos perioperatorios y a largo plazo.RESULTADOS:Se incluyeron 452 pacientes, 372 en el grupo abierto y 80 en el grupo mínimamente invasivo, con una mediana de seguimiento de 74 meses. Hubo diferencias significativas entre los grupos en términos de tratamiento con radiación neoadyuvante (67,5% del grupo abierto versus 81,3% del grupo mínimamente invasivo, p = 0,01), tiempo operatorio (media de 200 minutos versus 287 minutos, p < 0,0001) y la duración media de la estancia (9,5 días frente a 6,6 días, p < 0,0001). Las tasas generales de complicaciones fueron similares entre los grupos (34,5% versus 27,5%, p = 0,177). No hubo diferencias significativas en el número medio de ganglios linfáticos extraídos (21,7 versus 22,2 ganglios, p = 0,7), márgenes radiales circunferenciales (1,48 cm y 1,37 cm, p = 0,4), ni en la tasa de márgenes radiales afectados (10,8 cm). % versus 6,3%, p = 0,37). La supervivencia general a 5 años fue del 70% en el grupo abierto frente al 80% en el grupo mínimamente invasivo (p = 0,344), mientras que la tasa de supervivencia libre de enfermedad a 5 años en el grupo abierto fue del 63,2% frente al 77,6% en el grupo mínimamente invasivo (p = 0,09).LIMITACIONES:Experiencia en una institución de referencia única.CONCLUSIONES:Si bien ambos tienen resultados perioperatorios similares, el enfoque mínimamente invasivo, beneficia a los pacientes con estadía más corta y menor riesgo de infecciones de la herida quirúrgica. Ambos enfoques, producen una calidad técnica oncológica similar en términos de ganglios linfáticos extraídos y estado de los márgenes, y tienen resultados oncológicos comparables a largo plazo. Consulte Video Resumen en http://links.lww.com/DCR/B754. (Traducción - Dr. Fidel Ruiz Healy).

Mechanical vs Bioprosthetic Aortic Valve Replacement in Patients Younger Than 70 Years of Age: A Hazard Ratio Meta-analysis.

BACKGROUND: The choice between mechanical valves (MVs) and bioprosthetic valves (BVs) in patients undergoing aortic valve surgery is complex, requiring a balance between the inferior durability of BV and the indicated long-term anticoagulation therapy with MV. This is especially challenging in the middle age group (< 70 years), which has seen an increased use of BV over recent years. METHODS: A meta-analysis of randomised controlled trials (RCTs), observational studies using propensity score matching (PSM) and inverse probability weighting (IPW) was conducted to examine the clinical outcomes of patients < 70 years of age undergoing aortic valve replacement. The primary outcome was overall long-term mortality. Secondary outcomes included bleeding events, reoperation, systemic thromboembolism, and cerebrovascular accident. RESULTS: Fifteen studies (1 RCT, 12 PSM studies, and 2 IPW studies; aggregated sample size 16,876 patients) were included. Median follow-up was 7.8 years. Mortality was higher with BVs vs MVs (hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.00-1.49), as was reoperation (HR 3.05, 95% CI 2.22-4.19). Bleeding risk was lower with BVs (HR 0.58, 95% CI 0.48-0.69), and the risk of stroke was similar in both valve types (HR 0.96, 95% CI 0.83-1.11) CONCLUSIONS: This broadest meta-analysis comparing BV and MV suggests a survival benefit for MVs in patients < 70 years of age. This should lead to reassessment of current patterns used in the choice of valves for patients < 70 among the cardiothoracic surgery community.

Breast Implants: Common Questions and Answers.

Breast implants are used for a wide range of cosmetic and reconstructive purposes. In addition to breast augmentation, implants can be used for postmastectomy breast reconstruction, correction of congenital breast anomalies, breast or chest wall deformities, and male-to-female top surgery. Breast implants may confer significant benefits to patients, but several factors are important to consider preoperatively, including the impact on mammography, future lactation, and potential long-term implant complications (e.g., infection, capsular contracture, rupture, and the need for revision, replacement, or removal). A fundamental understanding of implant monitoring is also paramount to implant use. Patients with silicone breast implants should undergo routine screening for implant rupture with magnetic resonance imaging or ultrasonography completed five to six years postoperatively and then every two to three years thereafter. With the exception of complications, there are no formal recommendations regarding the timing of breast implant removal or exchange. Women with unilateral breast swelling should be evaluated with ultrasonography for an effusion that might indicate breast implant-associated anaplastic large cell lymphoma. There are no specific breast cancer screening recommendations for patients with breast implants, but special mammographic views are indicated to enhance accuracy. Although these discussions are a routine component of consultation and postoperative follow-up for plastic surgeons performing these procedures, family physicians should have a working knowledge of implant indications, characteristics, and complications to better counsel their patients, to ensure appropriate screening, and to coordinate care after surgery.

Surveillance Imaging Following Acute Type A Aortic Dissection.

BACKGROUND: Survivors of acute type A aortic dissection (ATAAD) repair remain at risk for long-term complications. Guidelines recommend postoperative imaging surveillance, but adherence is uncertain. OBJECTIVES: The aim of this study was to define the real-world frequency of postoperative imaging and characterize long-term outcomes of ATAAD. METHODS: Population-based administrative health databases for Ontario, Canada, were linked to identify patients who underwent ATAAD repair and survived at least 90 days. Guideline-directed imaging surveillance (GDIS) was defined as undergoing a computed tomographic or magnetic resonance imaging scan at 6 and 12 months postoperatively and then annually thereafter. Multivariable time-to-event analysis explored the associations between GDIS and all-cause mortality and reintervention. RESULTS: A total of 888 patients who survived urgent ATAAD repair between April 1, 2005, and March 31, 2018, were included. Median follow-up after ATAAD repair was 5.2 years (interquartile range: 2.4-7.9 years). A total of 14% patients received GDIS throughout follow-up. At 6 years, 3.9% of patients had received GDIS. The mortality rate was 4% at 1 year, 14% at 5 years, and 29% at 10 years. Incidence of aortic reintervention was 3% at 1 year, 9% at 5 years, and 17% at 10 years; the majority of these were urgent (68%), and they carried a 9% 30-day mortality rate. Greater adherence to GDIS was associated with mortality (hazard ratio: 1.08; 95% confidence interval: 1.05-1.11) and reintervention (hazard ratio: 1.04; 95% confidence interval: 1.01-1.07). CONCLUSIONS: Adherence to GDIS following ATAAD repair is poor, while long-term mortality and reinterventions remain substantial. Further research is needed to determine if guidelines should be modified.

Right ventricular outflow tract abnormalities in monochorionic twin pregnancies without twin-to-twin transfusion syndrome: Prenatal course and postnatal long-term outcomes.

OBJECTIVES: Right ventricular outflow tract abnormalities (RVOTA) have been mostly reported in recipient twins (RT) of monochorionic/diamniotic (MC/DA) twin pregnancies with twin-to-twin transfusion syndrome (TTTS). Aim of the study was to describe RVOTA detected in MC/DA pregnancies without TTTS. METHODS: Cases of RVOTA were retrieved from our database among all MC/DA pregnancies without TTTS from 2009 to 2018. RESULTS: Out of 891 MC/DA twin pregnancies without TTTS, 14 (1.6%) were associated with RVOTA: 10 pulmonary stenosis (PS), one steno-insufficiency, one insufficiency and two atresia (PA). In 93% of cases (13/14), pregnancy was complicated either by amniotic fluid discrepancy (AFD) or by TAPS or mostly by selective fetal growth restriction (sFGR) (11/13: 85%), involving predominantly (10/11: 91%) the large twin, with high incidence (9/11: 82%) of sFGR and AFD coexistence. Eight out of 14 (57%) survived after the perinatal period (7 PS, 1 PA). Five (62%) underwent pulmonary balloon valvuloplasty, whereas 3 children still showed persistent mild PS at cardiac follow up after 1 year of life. CONCLUSIONS: RVOTA can occur in MC/DA pregnancies without TTTS, particularly when other complications coexist. In complicated cases specialized fetal echocardiographic evaluation is recommended during pregnancy; RVOTA cases should be delivered in a tertiary level center, where cardiologists are available.

Differential DNA methylation and changing cell-type proportions as fibrotic stage progresses in NAFLD.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is characterized by changes in cell composition that occur throughout disease pathogenesis, which includes the development of fibrosis in a subset of patients. DNA methylation (DNAm) is a plausible mechanism underlying these shifts, considering that DNAm profiles differ across tissues and cell types, and DNAm may play a role in cell-type differentiation. Previous work investigating the relationship between DNAm and fibrosis in NAFLD has been limited by sample size and the number of CpG sites interrogated. RESULTS: Here, we performed an epigenome-wide analysis using Infinium MethylationEPIC array data from 325 individuals with NAFLD, including 119 with severe fibrosis and 206 with no histological evidence of fibrosis. After adjustment for latent confounders, we identified 7 CpG sites whose DNAm associated with fibrosis (p < 5.96 × 10-8). Analysis of RNA-seq data collected from a subset of individuals (N = 56) revealed that gene expression at 288 genes associated with DNAm at one or more of the 7 fibrosis-related CpGs. DNAm-based estimates of cell-type proportions showed that estimated proportions of natural killer cells increased, while epithelial cell proportions decreased with disease stage. Finally, we used an elastic net regression model to assess DNAm as a biomarker of fibrotic stage and found that our model predicted fibrosis with a sensitivity of 0.93 and provided information beyond a model based solely on cell-type proportions. CONCLUSION: These findings are consistent with DNAm as a mechanism underpinning or marking fibrosis-related shifts in cell composition and demonstrate the potential of DNAm as a possible biomarker of NAFLD fibrosis.