Outcomes after Surgery for Endocarditis among Intravenous Drug Users and Nonusers.

BACKGROUND: The optimal treatment strategy for intravenous drug users (IVDU) with infective endocarditis (IE) is controversial. We therefore sought to investigate outcomes among IVDUs after surgery for IE. METHODS: We retrospectively reviewed all 192 consecutive patients who underwent an operation for IE between 2005 and 2016 in the Helsinki University Hospital. Forty-seven patients (24.5%) were IVDUs and 145 (75.5%) were non-IVDUs. Mortality and reinfection and reoperation rates were evaluated. RESULTS: IVDUs were younger (29.9 vs. 63.8 years, p < 0.001) and had less cardiovascular risk factors and lower EuroSCORE II (4.3 vs. 7.3%, p < 0.001), but Staphylococcus aureus infection (66.0 vs. 23.4%, p < 0.001), tricuspid valve endocarditis (34.0 vs. 2.8%, p < 0.001), and liver disease (63.8 vs. 2.8%, p < 0.001) occurred more often in IVDUs than in non-IVDUs. Thirty-day mortality of IVDUs was 8.5% and that of non-IVDUs was 6.9% (p = 0.711). Survival of IVDUs at 5 years was 70.8 ± 7.4% and survival of non-IVDUs was 67.9 ± 4.7% (p = 0.678). Relative to an age- and sex-matched general population, IVDUs had 58.6 (95% confidence interval [CI]: 33.7-101.9; p < 0.001) and non-IVUD 4.4 (95% CI: 3.1-6.2; p < 0.001) standardized mortality ratio. IVDUs had a higher reinfection rate at 5 years (25.8 ± 7.7% vs. 3.0 ± 1.7%, p < 0.001) and a higher early reoperation rate than non-IVDUs (10.6 vs. 1.4%, p = 0.003). CONCLUSIONS: IVDUs and non-IVDUs had comparable survival at 5 years, but IVDUs had a very significantly increased risk of death in comparison to an age- and sex-matched general population. IVDUs had higher reinfection and early reoperation rates. Survival was poor after medically treated reinfection.

Growth of unrepaired hypoplastic proximal aortic arch and reintervention rate after aortic coarctation repair.

BACKGROUND: Treatment of tubular hypoplasia of the aortic arch (THAA) associated with aortic coarctation (CoA) remains controversial. We aimed to evaluate growth of unrepaired hypoplastic proximal aortic arches (PAAs) after surgical repair for CoA. METHODS: Preoperative and follow-up echocardiographic images of 139 patients who underwent CoA repairs from 2005 to 2012 were reviewed. THAA was defined as PAA z-score <-3 and non-THAA group z-score ≥-3. Reintervention rates due to aortic obstruction were assessed using competing risk models and diameters of the aorta were compared with Mann-Whitney U tests. RESULTS: Fifty patients (36%) had THAA and 89 (64%) had non-THAA. The survival rate was 94% at 10 years. The overall reintervention rate at 10 years was 9% in the THAA group and 16% in the non-THAA group (P = .54). The catheter reintervention rate at ten years was 2% in the THAA group and 16% in the non-THAA group (P = .031). The surgical reintervention rate at ten years was 7% in the THAA group and 0% in the non-THAA group (P = .016). All 4 patients who required surgical reintervention were in the THAA group and 3 patients with PAA obstruction had preoperative PAA z-scores -3.6, -4.2, and -4.3. Follow-up echocardiograms showed PAA catch-up growth in the THAA group compared with the non-THAA group (preoperative z-score of -3.6 vs -2.3, and at 7 years of -1.1 vs -1.2; P < .001). CONCLUSIONS: Unrepaired PAA hypoplasia grows after CoA repair. Reintervention rates were comparable between groups but those with THAA had higher surgical reintervention rates.

Ectopic germinal centers in the thymus accurately predict prognosis of myasthenia gravis after thymectomy.

The ability of thymic histopathology to predict the long-term impact of thymectomy in non-thymomatous myasthenia gravis (NTMG) is mainly uncharted. We applied digital pathology to quantitatively characterize differences of thymic histology between early-onset (EOMG) and late-onset MG (LOMG) and to investigate the role of thymic changes for thymectomy outcomes in MG. We analyzed 83 thymic H&E slides from thymectomized NTMG patients, of which 69 had EOMG and 14 LOMG, using digital pathology open-access software QuPath. We compared the results to the retrospectively assessed clinical outcome at two years after thymectomy and at the last follow-up visit where complete stable remission and minimal use of medication were primary outcomes. The automated annotation pipeline was an effective and reliable way to analyze thymic H&E samples compared to manual annotation with mean intraclass correlation of 0.80. The ratio of thymic tissue to stroma and fat was increased in EOMG compared to LOMG (p = 8.7e-07), whereas no difference was observed in the ratio of medulla to cortex between these subtypes. AChRAb seropositivity correlated with the number of ectopic germinal centers (eGC; p = 0.00067) but not with other histological areas. Patients with an increased number of eGCs had better post-thymectomy outcomes at two years after thymectomy (p = 0.0035) and at the last follow-up (p = 0.0267). ROC analysis showed that eGC area predicts thymectomy outcome in EOMG with an AUC of 0.79. Digital pathology can thus help in providing a predictive tool to the clinician, the eGC number, to guide the post-thymectomy treatment decisions in EOMG patients.

Outcomes of surgery for extensive infective endocarditis.

OBJECTIVE: Extensive infective endocarditis (EIE) involving the valve annulus or the intervalvular fibrous body (IFB) is a treatment challenge. We sought to clarify the outcomes of patients undergoing surgery for EIE. METHODS: We retrospectively reviewed all 197 consecutive patients who underwent an operation for infective endocarditis (IE) between 2005 and 2016 in the Helsinki University Hospital. Thirty-five (18%) patients had EIE, of which 17 (9%) infection extended to IFB. RESULTS: Patients with EIE had higher EuroSCORE II (24.4% vs. 12.4% p < .001), higher frequency of diabetes (29% vs. 13% p = .017), more often NYHA Class IV (83% vs. 56% p = .02), aortic (97% vs. 45% p < .001), multivalve (40% vs. 11% p < .001), and prosthetic valve IE (37% vs. 9% p < .001), and underwent more often emergency surgery (46% vs. 29% p = .042). Thirty-day mortality was 9% in the EIE group and 7% in the non-EIE group (p = .720). Survival of patients with EIE at 5 years was 60% and with non-EIE 71% (p = .029). The frequency of complications was higher in EIE (54%) than in non-EIE patients (25%) (p < .001), due to the higher need for permanent pacemaker implantations (34% vs. 4% p < .001). Freedom from re-operations at 5 years was 91% in the EIE group and 97% in the non-EIE group (p = .203). CONCLUSIONS: Early mortality of surgery for EIE was comparable with non-EIE. Midterm survival was lower after surgery for EIE than after surgery for non-EIE but there was no difference in survival of patients with IE limited to the valve annulus amenable to patch repair and patients with endocarditis requiring IFB reconstruction.

Outcome of valve sparing root replacement for diverse indications.

OBJECTIVES: We report the mid-term outcomes of valve-sparing aortic root replacement (VSRR) in a cohort including patients with bicuspid aortic valve (BAV), connective tissue disorder (CTD), aortic dissection (AD), and congenital heart disease (CHD). Design. From 2005 to 2017, 174 patients underwent VSRR with the reimplantation technique. The mean age was 46 ± 14 years. The mean follow-up time was 4.8 ± 2.8 years. The indication for operation was aortic aneurysm for 127 (73%), aortic insufficiency (AI) for 38 (22%), and AD for 9 patients (5%). Preoperatively, 53 patients (31%) had ≥ moderate AI. BAV, CTD (Marfan or Loyes-Dietz), previous Ross procedure, or CHD was present in 57 (33%), 28 (16%), 7 (4%) and 12 patients (7%), respectively. Concomitant aortic valve repair was performed for 103 patients (59%). Results. Thirty-day mortality was zero. Four patients underwent aortic valve replacement (AVR) during follow-up. Kaplan-Meier estimates for survival, freedom from AVR, and freedom from ≥ moderate AI or reoperation were 96, 98, and 97% at 5 years. There was no difference in survival, freedom from AVR, or freedom from ≥ moderate AI or reoperation in patients with and without BAV, CTD, leaflet repair, or preoperative ≥ moderate AI. In Cox regression analysis, BAV, CTD, aortic valve repair, preoperative ≥ moderate AI, or aortic dimension were not risk factors for reoperation or valve dysfunction. Conclusions. Mid-term outcomes of VSRR for patients with diverse indications in terms of survival, reoperation rate, and valve dysfunction rate were excellent in a center with a limited annual volume of VSSR.

Incidence and impact of chronic lung allograft dysfunction after lung transplantation - single-center 14-year experience.

Objectives. Lung transplantation remains the only available treatment option for many end-stage lung diseases. We evaluated our long-term lung transplantation results and the impact of chronic lung allograft dysfunction (CLAD). Design. Adult de novo lung transplants (2003-2015, n=175) in a nationwide single transplant center were retrospectively analyzed. Kaplan-Meier survival and Cox regression analysis were used to evaluate the effect of CLAD. Results. Recipient and graft 1-, 5- and 10-year survival estimates were 94%, 79% and 64%, and 93%, 75% and 59%, respectively. CLAD affected 43% of patients at a median of 2.3 years after transplantation, and impaired recipient (p = .03) and graft survival (p = .001) with the most advanced CLAD stage, and restrictive CLAD phenotype, resulting in worst graft survival. CLAD was the primary cause of death in 54% of all patients, and in 80% of patients with an established CLAD diagnosis. CLAD, high-risk cytomegalovirus serostatus, and recipient preoperative sensitization increased graft loss hazard ratio. CLAD was the only significant investigated risk factor for graft loss in multivariate regression analysis. Conclusions. Although very favourable lung transplant patient long-term survival was achieved, CLAD significantly impaired recipient and graft survival. Identification of risk factors and therapeutic options for CLAD may further improve lung transplantation results.

Unilateral pulmonary oedema after minimally invasive and robotically assisted mitral valve surgery.

OBJECTIVES: Unilateral pulmonary oedema (UPO) is a severe complication of minimally invasive cardiac surgery. UPO rates and UPO-related mortality vary considerably between different studies. Due to lack of consistent diagnostic criteria for UPO, the aim of this study was to create a reproducible radiological classification for UPO. Also, risk factors for UPO after robotic and minimally invasive mitral valve operations were evaluated. METHODS: Two hundred and thirty-one patients who underwent elective minimally invasive mitral valve surgery between January 2009 and March 2017 were evaluated. Chest radiographs of the first postoperative morning were categorized into 3 UPO grades based on the severity of radiological signs of pulmonary oedema described in this study. The radiographs were analysed by 2 independent radiologists and interobserver agreement was evaluated. The clinical significance of the classification was evaluated by comparing postoperative PaO2/FiO2 values and total ventilation times between the different UPO grades. Also, multivariable logistic regression analysis was employed to identify risk factors for UPO. RESULTS: Interobserver agreement was substantial (Kappa = 0.780). Median total ventilation times were significantly longer with increasing severity of UPO, 15 (interquartile range 12-18) h for no UPO, 18 (interquartile range 15-24) h for grade I UPO and 25 (interquartile range 21-31) h for grade II UPO. Pulmonary hypertension [adjusted odds ratios (AOR) 2.51, 95% confidence intervals (CI) 1.43-4.40; P = 0.001], moderate or severe heart failure (AOR 2.88, 95% CI 1.27-6.53; P = 0.011), body mass index (AOR 1.14, 95% CI 1.02-1.28; P = 0.017) and cardiopulmonary bypass time (AOR 1.02, 95% CI 1.01-1.03; P < 0.001) were identified as independent risk factors for UPO and robotic approach (AOR 0.27, 95% CI 0.12-0.62; P = 0.002) as protective against UPO. CONCLUSIONS: Due to the variability of the diagnostic criteria for UPO in previous studies, a radiological classification for UPO is required to reliably assess the rates and risk factors for UPO. The radiological classification described in this study demonstrated high interobserver agreement and correlated with total ventilation times and postoperative PaO2/FiO2 values.

Outcome of early vs delayed surgery for infective mitral endocarditis.

BACKGROUND AND AIM OF THE STUDY: Timing of surgery for infective endocarditis is controversial. The objective of this study was to report the outcomes of early vs delayed surgery (DS) of mitral endocarditis. METHODS: We retrospectively reviewed all patients treated surgically for mitral endocarditis between 2005 and 2016 in a single center. We analyzed midterm outcomes of early surgery (ES; surgery within 7 days or less of prior directed antibiotic treatment) in comparison to DS (surgery after more than 7 days of prior directed antibiotic treatment). RESULTS: Survival of all patients was 87% at one and 72% at 5 years. Mean follow-up time was 4.0 ± 3.1 years. Thirty-three (36.3%) patients were in the ES and 58 (63.7%) were in the DS group. Patients with ES were younger (47.4 vs 55.3 years), were in New York Heart Association class III or IV more frequently (97.0 vs 65.5%), and had higher EuroScore2 (15.6 vs 8.6%). The ES group had lower freedom from valve reoperation (98.2 vs 87.2%; P = .035) and the composite endpoint of >2 + regurgitation or reoperation at 5 years (98.2 vs 72.7%; P = .004). CONCLUSIONS: ES was associated with a higher rate of reoperations and the composite endpoint of recurrent MR or reoperation.

[Treatment of adult tracheal stenosis]. / Aikuisten henkitorven ahtaumien kirurginen hoito.

Tracheal stenosis is a rare condition with symptoms mimicking asthma or COPD. The most frequent benign tracheal stenosis is caused by lesions related either to intubation or tracheostomy. Primary tracheal tumors or secondary malignancies such as locally advanced esophageal cancer are rare causes. As a rare disease the diagnosis and treatment are often delayed. Endoscopic therapy is the primary treatment for tracheal stenosis. Tracheal resection is indicated in resectable malignant tumors and in benign stenosis which do not respond to endoscopic treatment or require repeated therapy. In these situations, surgery provides a safe and a long-term solution. Currently, surgery is rarely an option in long-segment tracheal lesions. Advances in stem cell technology, tracheal transplantation and tissue engineering may, however, provide a solution for these problems in the future.

Aerobic fitness does not modify the effect of FTO variation on body composition traits.

PURPOSE: Poor physical fitness and obesity are risk factors for all cause morbidity and mortality. We aimed to clarify whether common genetic variants of key energy intake determinants in leptin (LEP), leptin receptor (LEPR), and fat mass and obesity-associated (FTO) are associated with aerobic and neuromuscular performance, and whether aerobic fitness can alter the effect of these genotypes on body composition. METHODS: 846 healthy Finnish males of Caucasian origin were genotyped for FTO (rs8050136), LEP (rs7799039) and LEPR (rs8179183 and rs1137101) single nucleotide polymorphisms (SNPs), and studied for associations with maximal oxygen consumption, body fat percent, serum leptin levels, waist circumference and maximal force of leg extensor muscles. RESULTS: Genotype AA of the FTO SNP rs8050136 associated with higher BMI and greater waist circumference compared to the genotype CC. In general linear model, no significant interaction for FTO genotype-relative VO(2)max (mL·kg(-1)·min(-1)) or FTO genotype-absolute VO(2)max (L·min(-1)) on BMI or waist circumference was found. Main effects of aerobic performance on body composition traits were significant (p<0.001). Logistic regression modelling found no significant interaction between aerobic fitness and FTO genotype. LEP SNP rs7799039, LEPR SNPs rs8179183 and rs1137101 did not associate with any of the measured variables, and no significant interactions of LEP or LEPR genotype with aerobic fitness were observed. In addition, none of the studied SNPs associated with aerobic or neuromuscular performance. CONCLUSIONS: Aerobic fitness may not modify the effect of FTO variation on body composition traits. However, relative aerobic capacity associates with lower BMI and waist circumference regardless of the FTO genotype. FTO, LEP and LEPR genotypes unlikely associate with physical performance.

Common genetic variation in the IGF1 associates with maximal force output.

PURPOSE: We clarified the effect of insulin-like growth factor-1 (IGF1), IGF-binding protein-3 (IGFBP3), interleukin-6 (IL6), and its receptor (IL6R) gene variants on muscular and aerobic performance, body composition, and on circulating levels of IGF-1 and IL-6. Single nucleotide polymorphisms (SNPs) may, in general, influence gene regulation or its expression, or the structure and function of the corresponding protein, and modify its biological effects. IGF-1 is involved in the anabolic pathways of skeletal muscle. IL-6 plays an important role in muscle energy homeostasis during strenuous physical exercise. METHODS: Eight hundred forty-one healthy Finnish male subjects of Caucasian origin were genotyped for IGF1 (rs6220 and rs7136446), IGFBP3 (rs2854744), IL6 (rs1800795), and IL6R (rs4537545) SNPs, and studied for associations with maximal force of leg extensor muscles, maximal oxygen consumption, body fat percent, and IGF-1 and IL-6 levels. Analytic methods included dynamometer, bicycle ergometer, bioimpedance, ELISA, and polymerase chain reaction assays. RESULTS: All investigated SNPs conformed to Hardy-Weinberg equilibrium with allele frequencies validated against CEU population. Genotype CC of rs7136446 associated with higher body fat and increased maximal force production. Genotype CC of the IGFBP3 SNP rs2854744 and TT genotype of the IL6R SNP rs4537545 associated with higher IL-6 levels. In logistic regression analysis, allele C of the rs2854744 decreased odds for lower body fat. None of the studied SNPs associated with aerobic performance. CONCLUSIONS: Our data suggest that common variation in the IGF1 gene may affect maximal force production, which can be explained by the role of IGF-1 in the anabolic pathways of muscle and neurotrophy. Variations in the IGF1 and IGFBP3 gene may result in higher body fat and be related to alterations of IGF-1-mediated tissue growth.

Genetic variations of leptin and leptin receptor are associated with body composition changes in response to physical training.

Leptin regulates body weight, metabolism, and tissue adaptations to environmental stressors. We examined the association of single nucleotide polymorphism (SNP) of leptin promoter G-2548A (rs7799039) and leptin receptor Gln223Arg (rs1137101) with body composition, plasma leptin levels, and peak oxygen uptake (VO(2)peak) in response to 8 weeks of physical training in 48 male military conscripts. AA homozygotes of leptin promoter SNP-2548 showed higher body fat and BMI values than G allele carriers. Acute exercise decreased leptin levels in G allele carriers, but increased in AA homozygotes. Physical training significantly decreased BMI values and also a tendency for decreased plasma leptin levels was observed in all subjects. In G allele carriers, BMI loss was mainly due to decreased fat mass, whereas in AA homozygotes due to loss of fat-free mass. Training increased VO(2)peak in all subjects with most prominent effects in G allele carriers. Regarding leptin receptor SNP, there were no statistically significant differences in BMI values between the genotype groups at baseline or after physical training. Our results suggest that physical training-induced alterations in body composition and plasma leptin may be influenced by a genetic variation of leptin promoter but not of leptin receptor.

A common variation in the promoter region of interleukin-6 gene shows association with exercise performance.

UNLABELLED: Skeletal muscle-derived interleukin-6 (IL-6) is a pleiotropic cytokine which regulates body metabolism during strenuous physical exercise. OBJECTIVE: The effect of a potentially functional single nucleotide polymorphism (SNP) -174G/C of the IL6 gene (rs1800795) promoter was examined on maximal oxygen uptake (VO2max), body mass index (BMI) and plasma IL-6 levels in response to physical training. Fifty four male military conscripts were studied for 8 weeks during their basic training. At weeks 1, 5 and 8, VO2max and anthropometrics were measured, and blood samples collected before and after acute aerobic exercise. Acute exercise increased plasma IL-6 in subjects with genotype CG. Moreover, during the 8-week training period, a tendency for increased plasma IL-6 was observed in subjects with this genotype. VO2max values increased in all genotype groups, but subjects with genotype CG made the greatest gains in VO2max. Training significantly decreased BMI only in subjects with genotype CG. Our findings suggest that the allele C may have an effect on plasma IL-6 response to acute exercise in healthy male subjects. Exercise training has a favourable effect on VO2max and BMI, with the most prominent effects in subjects with genotype CG. Thus we conclude that this SNP may account for individual response to exercise training. Key pointsAllele C of the IL6 promoter SNP -174G/C may have an effect on plasma IL-6 response to acute exercise.All subjects responded to physical exercise, but the improvement in VO2max and decrease in BMI after training are more pronounced in the individuals with genotype CG, hence the IL6 promoter SNP -174G/C may have an influence on training responses.The small number of subjects investigated in the present study warrants further research to confirm these findings in large cohorts.