Objectives: Data on national patterns of care for patients with superior sulcus tumors (SST) is currently lacking. We investigated the distribution of surgical care and outcome for patients with... Show moreObjectives: Data on national patterns of care for patients with superior sulcus tumors (SST) is currently lacking. We investigated the distribution of surgical care and outcome for patients with SST in the Netherlands. Material and methods: Data was retrieved from the Dutch Lung Cancer Audit for Surgery (DLCA-S) for all patients undergoing resection for clinical stage IIB-IV SST from 2012 to 2019. Because DLCA-S is not linked to survival data, survival for a separate cohort (2015-2017) was obtained from the Netherlands Cancer Registry (NCR). Results: In the study period, 181 patients had SST surgery, representing 1.03% (181/17488) of all lung cancer pulmonary resections. For 2015-2017, the SST resection rate was 14.4% (79/549), and patients with stage IIB/III SST treated with trimodality had a 3-year overall survival of 67.4%. 63.5% of patients were male, and median age was 60 years. Almost 3/4 of tumors were right sided. Surgery was performed in 20 hospitals, with average number of annual resections ranging from < 1 (n = 17) to 9 (n = 1). 39.8% of resections were performed in 1 center and 63.5% in the 3 most active centers. 12.7% of resections were extended (e.g. vertebral resection). 85.1% of resections were complete (R0). Morbidity and 30-day mortality were 51.4% and 3.3% respectively. Despite treating patients with a higher ECOG performance score and more extended resections, the highest volume center had rates of morbidity/mortality, and length of hospital stay that were comparable to those of the medium volume (n = 2) and low-volume centers (n = 1). Conclusion: In the Netherlands, surgery for SST accounts for about 1% of all lung cancer pulmonary resections, the number of SST resections/hospital/year varies widely, with most centers performing an average of < 1/year. Morbidity and mortality are acceptable and survival compares favourably with the literature. Although further centralisation is possible, it is unknown whether this will improve outcomes. Show less
Timmis, A.; Townsend, N.; Gale, C.P.; Torbica, A.; Lettino, M.; Petersen, S.E.; ... ; Vardas, P. 2020
Aims The 2019 report from the European Society of Cardiology (ESC) Atlas provides a contemporary analysis of cardiovascular disease (CVD) statistics across 56 member countries, with particular... Show moreAims The 2019 report from the European Society of Cardiology (ESC) Atlas provides a contemporary analysis of cardiovascular disease (CVD) statistics across 56 member countries, with particular emphasis on international inequalities in disease burden and healthcare delivery together with estimates of progress towards meeting 2025 World Health Organization (WHO) non-communicable disease targets.Methods and results In this report, contemporary CVD statistics are presented for member countries of the ESC. The statistics are drawn from the ESC Atlas which is a repository of CVD data from a variety of sources including the WHO, the Institute for Health Metrics and Evaluation, and the World Bank. The Atlas also includes novel ESC sponsored data on human and capital infrastructure and cardiovascular healthcare delivery obtained by annual survey of the national societies of ESC member countries. Across ESC member countries, the prevalence of obesity (body mass index >= 30 kg/m(2)) and diabetes has increased two- to three-fold during the last 30years making the WHO 2025 target to halt rises in these risk factors unlikely to be achieved. More encouraging have been variable declines in hypertension, smoking, and alcohol consumption but on current trends only the reduction in smoking from 28% to 21% during the last 20years appears sufficient for the WHO target to be achieved. The median age-standardized prevalence of major risk factors was higher in middle-income compared with high-income ESC member countries for hypertension {23.8% [interquartile range (IQR) 22.5-23.1%] vs. 15.7% (IQR 14.5-21.1%)}, diabetes [7.7% (IQR 7.1-10.1%) vs. 5.6% (IQR 4.8-7.0%)], and among males smoking [43.8% (IQR 37.4-48.0%) vs. 26.0% (IQR 20.9-31.7%)] although among females smoking was less common in middle-income countries [8.7% (IQR 3.0-10.8) vs. 16.7% (IQR 13.9-19.7%)]. There were associated inequalities in disease burden with disability-adjusted life years per 100 000 people due to CVD over three times as high in middle-income [7160 (IQR 5655-8115)] compared with high-income [2235 (IQR 1896-3602)] countries. Cardiovascular disease mortality was also higher in middle-income countries where it accounted for a greater proportion of potential years of life lost compared with high-income countries in both females (43% vs. 28%) and males (39% vs. 28%). Despite the inequalities in disease burden across ESC member countries, survey data from the National Cardiac Societies of the ESC showed that middle-income member countries remain severely under-resourced compared with high-income countries in terms of cardiological person-power and technological infrastructure. Under-resourcing in middle-income countries is associated with a severe procedural deficit compared with high-income countries in terms of coronary intervention, device implantation and cardiac surgical procedures.Conclusion A seemingly inexorable rise in the prevalence of obesity and diabetes currently provides the greatest challenge to achieving further reductions in CVD burden across ESC member countries. Additional challenges are provided by inequalities in disease burden that now require intensification of policy initiatives in order to reduce population risk and prioritize cardiovascular healthcare delivery, particularly in the middle-income countries of the ESC where need is greatest. Show less
Backer, J.A.; Wallinga, J.; Meijer, A.; Donker, G.A.; Hoek, W. van der; M. van boven 2019
In Africa, polyparasitism is the rule rather than the exception. The aim of this thesis was to get a detailed insight into the micro-geographical distribution and patterns of S. mansoni and S.... Show moreIn Africa, polyparasitism is the rule rather than the exception. The aim of this thesis was to get a detailed insight into the micro-geographical distribution and patterns of S. mansoni and S. haematobium co-infections, and how this affects host morbidity. A community-wide study was carried out in a co-endemic focus in the north of Senegal, combining epidemiological, ecological, immunological, and geographical analyses. This multidisciplinary approach led to several new insights. Spatial analyses showed significant clustering of Schistosoma infection and morbidity even on a micro scale; S. mansoni and S. haematobium hotspots were found in different sections of one community. Another major finding was that the presence of S. mansoni in co-infections might protect against S. haematobium-specific urinary tract morbidity. Furthermore, it was observed that S. haematobium antigens induced stronger cytokine responses than those of S. mansoni, indicating that the first species may be more immunogenic. The results of this thesis provide new leads for further research on disease etiology and underlying mechanisms in Schistosoma co-infections. Such knowledge is key to rationalizing and optimizing current schistosomiasis control strategies in co-endemic areas and to developing successful elimination strategies in the future. Show less
Twin-to-twin transfusion syndrome (TTTS) is a severe complication of monochorionic twin pregnancies associated with high perinatal mortality and morbidity rates. Placental vascular anastomoses,... Show moreTwin-to-twin transfusion syndrome (TTTS) is a severe complication of monochorionic twin pregnancies associated with high perinatal mortality and morbidity rates. Placental vascular anastomoses, almost invariably present in monochorionic placentas, are the essential anatomical substrate for the development of TTTS. TTTS is thought to result from unbalanced inter-twin blood flow between the donor twin and the recipient twin through the vascular anastomoses, leading to hypovolemia and oligohydramnios in the donor and hypervolemia and polyhydramnios in the recipient. Despite significant developments in the diagnosis, staging and management of TTTS, the pathogenesis of TTTS is still poorly understood and, most importantly, perinatal mortality and morbidity in TTTS remain strikingly high. In this thesis, several studies on TTTS are presented regarding various aspects of this disease, including studies on monochorionic placentas to investigate the pathogenesis of TTTS, description of a new form of chronic TTTS and the short and long-term outcome in TTTS treated with fetoscopic laser surgery. In Chapter 2, an overview of the literature is presented. This review analyzes the possible pathophysiologic mechanisms involved, discusses the latest findings in diagnosis, therapy and prognosis, and focuses on neonatal and pediatric morbidity associated with TTTS. In Chapter 3 we describe a novel technique to calculate the net feto-fetal blood flow through placental arterio-venous anastomoses in a case of TTTS treated with laser surgery and subsequent intrauterine transfusion. In this study we determined that the net blood flow through the five unidirectional arterio-venous anastomoses was approximately 28 ml/24h, much lower than previously measured with Doppler ultrasound. This finding may also explain the inaccuracy of Doppler flow measurements, as such low flow velocities cannot possibly be detected with current Doppler techniques. Measurements of anastomotic blood flow are of major importance for the validation and development of accurate computer modeling in TTTS. In Chapter 4 we studied the role of velamentous cord insertion and discordant placental sharing in the pathogenesis of TTTS by comparing monochorionic placentas with and without TTTS. Previously, several studies reported an increased incidence of velamentous cord insertions in TTTS placentas and suggested a direct relation between velamentous cord insertion, unequal placental sharing and the development of TTTS. In this study we examined 76 monochorionic placentas with TTTS and 63 monochorionic placentas without TTTS. The incidence of velamentous cord insertion (per fetus) in the TTTS group and the no-TTTS group was 13% and 14% (p = 0.79), respectively. Placental sharing discordance in the TTTS group and the no-TTTS group was 20% in both groups (p = 0.83). In the TTTS group, donor twins had more often a velamentous cord insertion than recipient twins (24% and 3%, respectively, P < 0.001) and smaller placental shares (44% and 56% respectively, p < 0.001)). Our findings suggest that velamentous cord insertion and smaller placental share in donor twins are a consequence of developing TTTS, rather than a cause of TTTS. In Chapter 5 the frequency of residual placental vascular anastomoses after fetoscopic laser surgery for TTTS was studied. Presence of residual anastomoses was investigated in relation to adverse outcome and to intertwin hemoglobin difference at birth. Residual anastomoses were detected in 33% (17/52) of placentas. Adverse outcome (fetal demise, neonatal death or severe cerebral injury) was similar in the groups with and without residual anastomoses, 18% (6/34) and 29% (20/70), respectively (p = 0.23). Large inter-twin hemoglobin differences (> 5 g/dL) were found in 65% (11/17) of cases with residual anastomoses and 20% (7/35) of cases without residual anastomoses (p < 0.01). The first conclusion of this study is that laser treatment needs to be improved as only 2/3 of monochorionic placentas are functionally __dichorionized__. The second conclusion is that residual anastomoses in this study are not associated with adverse outcome. Lack of association between residual anastomoses and adverse outcome may partly be due to the small size of the majority of residual anastomoses (< 1mm diameter in 64% of the cases) and the presence of __protective__ residual superficial anastomoses in 35% of the cases. Finally, we concluded that residual anastomoses are often associated with neonatal hematological complications. In Chapter 6 we describe two pairs of monochorionic twins without TTTS but with marked discordant hemoglobin levels. We named this new form of TTTS, the twin anemia-polycythemia sequence (TAPS). In the two reported TAPS cases, both donor twins were severely anemic requiring blood transfusion and both recipients were polycythemic, one requiring partial volume exchange transfusions. Inter-twin difference in reticulocyte counts was extremely high, suggesting a chronic form of inter-twin blood transfusion. Placental injection studies revealed a preponderance of very small (< 1 mm) arterio-venous anastomoses in one direction. Nowadays, routine prenatal measurements of middle cerebral artery peak systolic velocity using Doppler ultrasound are recommended after laser surgery to rule out fetal anemia or (iatrogenic) TAPS. We suggest that routine Doppler studies also be performed in uncomplicated monochorionic twin pregnancies without TOPS. Signs of fetal anemia in a monochorionic twin should then alert the perinatologist of the possibility of TAPS. TAPS should be diagnosed when a large inter-twin discordance in fetal or neonatal hemoglobin levels and reticulocyte counts is found, in the absence of TOPS. Placental injection studies may then reveal a preponderance of very small arterio-venous anastomoses. Discordant hemoglobin levels occur not only in chronic TTTS and in TAPS, but are also reported to occur in uncomplicated monochorionic pregnancies due to acute peripartum TTTS. In Chapter 7 we studied the inter-twin difference in hemoglobin levels at birth in monochorionic twins without TTTS compared to a control group of dichorionic twins, in relation to birth order and placental vascular anatomy. We found that hemoglobin differences occur more frequently in monochorionic twins without chronic TTTS than in dichorionic twins, but only when measured on the second day of life. Furthermore, hemoglobin differences in monochorionic twins are associated with birth order and with the presence of superficial vascular anastomoses. We found that second-born monochorionic twins have significantly higher hemoglobin values than first-born twins. Our findings support the hypothesis that second-born monochorionic twins are more likely to receive a large placental blood transfusion rather than lose blood into the placenta. We also report that hemoglobin differences in monochorionic twins are greater in the presence of superficial vascular anastomoses. In analogy to acute perimortem TTTS, it is conceivable that superficial vascular anastomoses may also be responsible for rapid placento-fetal blood transfusion during delivery. Chapter 8, 9 and 10 focus on the short-term outcome in TTTS treated with fetoscopic laser surgery. The neonatal outcome in TTTS survivors treated with laser at our center is presented in Chapter 8. We compared the outcome in a TTTS group after laser treament with a control group of monochorionic twins without TTTS delivered at our center. We found that neonatal mortality in the TTTS and no-TTTS group was 8% (6/76) and 3% (3/90) respectively (p = 0.03). Overall, the incidence of adverse neonatal outcome (neonatal mortality, major neonatal morbidity or severe cerebral lesions) in the TTTS and no-TTTS group was 26% (20/76) and 13% (12/90), respectively (RR = 1.97, 95% CI = 1.03 to 3.77). We concluded that the risk for adverse neonatal outcome is two-fold increased in TTTS treated with laser than in monochorionic twins without TTTS. Details on the short-term neurological outcome in TTTS survivors treated with fetoscopic laser surgery are presented in Chapter 9. Again we compared the results with a control group of monochorionic twins without TTTS. Incidence of antenatally acquired severe cerebral lesions in the TTTS group was 10% (8/84) and 2% (2/108) in the no-TTTS group (p = 0.02). Incidence of severe cerebral lesions at discharge was 14% (12/84) in the TTTS group and 6% (6/108) in the no-TTTS group (p = 0.04). Antenatal injury was responsible for severe cerebral lesions in 67% (8/12) of the TTTS group. We conclude that the incidence of severe cerebral lesions in TTTS treated with fetoscopic laser surgery is high and results mainly from antenatal injury. Details on the short-term cardiac outcome in TTTS survivors treated with fetoscopic laser surgery are presented in Chapter 10 and compared to a control group of monochorionic twins without TTTS. Echocardiography was performed within one week after delivery. At birth, blood pressure was measured in all survivors and endothelin-1 was determined in umbilical cord blood. Data on right ventricular outflow tract obstruction in TTTS treated with laser surgery at our center but delivered elsewhere were reviewed retrospectively from medical records. We found that the incidence of right ventricular outflow tract obstruction in recipients was 4% (3/75). We found no difference in afterload parameters between donors and recipients after laser treatment. We concluded that the incidence of congenital heart disease in TTTS survivors treated with fetoscopic laser occlusion of vascular anastomoses is around 5%, which is higher than in the general population (0.5%). In particular, the increased risk of right ventricular outflow tract obstruction in recipient twins warrants close cardiac monitoring during fetal and neonatal life. The long-term neurodevelopmental outcome in TTTS is presented in Chapter 11 and 12. Chapter 11 describes the long-term neurodevelopmental outcome in TTTS treated conservatively. All TTTS-cases admitted at our center between January 1990 and December 1998 were included in the study. Perinatal mortality was 50% (29/58). Neurological and mental development at school age was assessed during a home visit in all TTTS-survivors (n = 29). The incidence of adverse neurodevelopmental outcome in TTTS survivors was 21% (6/29) and was due to cerebral palsy (n = 6) and developmental delay (n = 5). The incidence of adverse neurodevelopmental outcome in the group of survivors who were treated with amnioreduction was 26% (5/19). Two of the four children born after intrauterine fetal demise of their co-twin had cerebral palsy. Chapter 12 describes the long-term neurodevelopmental outcome in TTTS treated with fetoscopic laser surgery. All TTTS-cases treated consecutively at our center between August 2000 and December 2003 were included in the study. Perinatal mortality was 30% (49/164). Neurological, mental and psychomotor development at 2 years of age was assessed in all TTTS-survivors (n = 115). Overall, the incidence of neurodevelopmental impairment was 17% (19/115) and was due to cerebral palsy (n = 8), mental developmental delay (n = 9), psychomotor developmental delay (n = 12) and deafness (n = 1). In both long-term follow-up studies, we concluded that neurodevelopmental delay in TTTS, regardless of type of antenatal treatment, is high and warrants long-term follow-up. In conclusion, although laser surgery appears to be the best available treatment option for TTTS, perinatal mortality and morbidity rates in TTTS treated with laser are still significant. More research and new developments are required to further improve the short and long-term outcome in TTTS. Show less
