The pre-diseased coronal alignment can be predicted from conventional radiographs taken of the varus arthritic knee.

INTRODUCTION: The concept of restoring the constitutional, pre-diseased alignment has gained lots of interest among knee surgeons. Previous attempts to use the contralateral limb to bridge the gap between the arthritic and the constitutional alignment were unsuccessful. We investigated the usability of a mathematical formula to predict the constitutional (pre-diseased) coronal alignment once arthritis has occurred. It is our hypothesis that by using the KL grade, CPAK classification and four radiographic measurements of the arthritic knee, the pre-diseased coronal alignment could be predicted. MATERIAL AND METHODS: Hundred arthritic patients with consecutive X-rays were used to determine a mathematical formula. Five alignment parameters were determined on full-length X-rays: HKA angle, mechanical lateral distal femoral angle (mLDFA), medial proximal tibial angle (MPTA), joint line convergence angle (JLCA) and the tibial joint line angle (TJLA). A refinement of the algorithm was implemented based on a reference cohort, consisted of 250 young adults aged between 20 and 27 years. Moreover, all knees were subdivided based on their CPAK-phenotype and the Kellgren-Lawrence scale (KL scale). An independent arthritic cohort of 289 patients scheduled for primary total knee arthroplasty was included to verify the accuracy of the predicted HKAs (HKAPRED). RESULTS: In CPAK type 1, the HKAPRED was 3.86° varus (STD 1.39) and the HKAYHA was 4.0° varus. In CPAK type 2, the HKAPRED was 1.68° varus (STD 1.95) compared to a HKAYHA of 1.34° (STD 0.81). The average constitutional HKA is not different in both CPAK 1 (p = 0.61) and CPAK 2 (p = 0.25), and the difference in the mean is estimated to be equal to - 0.14 (95CI - 0.68 to 0.40) in CPAK 1 and 0.35 (95CI - 0.06 to 0.75) in CPAK 2. CONCLUSION: Using the KL grade, CPAK classification and four radiographic measurements of the arthritic knee, the pre-diseased coronal alignment can be predicted in 80% of the varus knees with an accuracy of ≤ 0.5°. The predicted HKA (HKAPRED) can be very useful in the current and future clinical practice.

Primary constrained-condylar-knee designs outperform posterior-stabilized and cruciate-retaining designs in high-grade varus osteoarthritic knees during short-term follow-up: a pilot study.

INTRODUCTION: High-grade varus osteoarthrosis (OA) is characterized by a pronounced intra-articular varus deformity and associated insufficiency of the lateral ligamentous complex. When performing a total knee arthroplasty (TKA) in such a knee, traditionally the alignment is restored to neutral, and the medial soft tissue structures are released to compensate for the lateral laxity and balance the joint. However, another option would be to leave the medial soft tissues untouched and accept the lateral laxity but to compensate for it using an ML-stabilized constrained-condylar knee (CCK) design. Our aim was to prove our hypothesis that such knees would demonstrate better clinical stability and better functionality as well as subjective outcome scores. MATERIALS AND METHODS: We searched our bicenter database of 912 primary TKAs (from 2016 to 2019) for primary TKA patients with a preoperative varus alignment of > 8°. After inclusion, 60 patients were divided into three groups by implant design: CCK (n = 21), posterior-stabilized (PS) (n = 20) and cruciate-retaining (CR) (n = 19). Oxford Knee Score (OKS), Forgotten Joint Score (FJS), Knee Society Score (KSS), UCLA-activity score, ML instability scores and both radiographic and clinical data were compared between groups. RESULTS: ML stability was significantly better in CCK designs (86% grade 0) compared to CR (37% grade 0) (p = 0.004) but not PS (70% grade 0) designs. No grade II instability was present in CCK and PS implants compared to 16% of CR implants. KSS and UCLA-activity score were higher in CCK designs compared to PS (p = 0.027, p = 0.041) and CR designs (p < 0.001, p = 0.007). OKS and FJS were higher in CCK designs compared to CR (p = 0.025, p = 0.008) but not to PS. CONCLUSION: The use of a CCK design to compensate for the lateral laxity in high-grade varus OA knees allowed to refrain from a medial release. CCK designs displayed improved clinical stability and better functionality as well as subjective outcome scores compared to less-constrained designs.

Improving IUI success by performing modified slow-release insemination and a patient-centred approach in an insemination programme with partner semen: a prospective cohort study.

BACKGROUND: Pregnancy rates after in vitro fertilisation (IVF) treatment continue to improve, while intrauterine insemination (IUI) programmes show no such trend. There is a need to improve success rates with IUI to retain it as a viable option for couples who prefer avoiding IVF as a first line treatment. OBJECTIVE: To investigate if a modified slow-release insemination (SRI) increases the clinical pregnancy rate (CPR) after intrauterine insemination (IUI) with partner semen. MATERIALS AND METHODS: This was a prospective cohort study in a Belgian tertiary fertility centre. Between July 2011 and December 2018, we studied data from an ongoing prospective cohort study including 989 women undergoing 2565 IUI procedures for unexplained or mild/moderate male infertility. These data were analysed in order to study the importance of different covariates influencing IUI success. Generalised estimating equations (GEEs) were used for statistical analysis. Results of two periods (2011-2015, period 1 and 2016-2018, period 2) were examined and compared. From January 2016 (period 2) onwards, a standardised SRI procedure instead of bolus injection of sperm was applied. The primary outcome parameter was the difference in clinical pregnancy rate (CPR) per cycle between period 1 (bolus IUI) and period 2 (modified SRI). Secondary outcome results included all other parameters significantly influencing CPR after IUI. RESULTS: Following the application of modified SRI the CPR increased significantly, from 9.03% (period 1) to 13.52% (period 2) (p = 0.0016). Other covariates significantly influencing CPR were partner's age, smoking/non-smoking partner, BMI patient, ovarian stimulation protocol and Inseminating Motile Count (after semen processing). CONCLUSIONS: Conclusions: The intentional application of modified slow-release of processed semen appears to significantly increase CPRs after IUI with homologous semen. Future studies should investigate whether SRI, patient-centred measures, or a combination of both, are responsible for this improvement.

High risk of tunnel convergence during combined anterior cruciate ligament and anterolateral ligament reconstruction.

PURPOSE: To assess the risk of femoral tunnel convergence in combined anterior cruciate ligament (ACL) and anterolateral ligament (ALL) reconstructions. The hypothesis was that a more proximal and anterior orientation of the ALL femoral tunnel should reduce the risk of convergence with the ACL femoral tunnel. METHODS: 15 fresh-frozen cadaver knees were examined. An anatomic ACL femoral tunnel was drilled arthroscopically in each specimen and ALL tunnels were made in two directions: (1) 0° coronal angulation and 20° axial angulation, (2) 30° coronal angulation and 30° axial angulation. Computed tomography scans were performed to investigate tunnel convergence and to measure the minimal distance between tunnels, tunnel length and the LFC width. RESULTS: Tunnel convergence occurred in 20 of 30 cases (67%). Convergence was significantly reduced when tunnels were drilled at 30° coronal and 30° axial angulation (p < 0.05). The mean length of the ALL tunnel was 15.9 mm [95% CI (13.6; 18.1)] and was independent of ALL tunnel angulation. The mean minimal distance between the ALL and ACL tunnel was 3.1 mm [95% CI (2.1; 4.1)]. The odds ratio for tunnel convergence was 3.5 for small LFC, relative to large LFC (n.s.) CONCLUSION: A high risk of tunnel convergence was observed when performing combined ACL and ALL reconstructions. The clinical relevance of this work is that the occurrence of tunnel conflicts can be reduced by aiming the ALL tunnel in a more proximal and anterior direction. Surgeons should be aware of this, since tunnel convergence could jeopardize the ACL reconstruction and fixation.

Pregnant after assisted reproduction: a risk pregnancy is born! 18-years perinatal outcome results from a population-based registry in Flanders, Belgium.

BACKGROUND: Although the increased risk for perinatal morbidity and mortality of babies born after ART is largely attributed to a higher rate of multiple gestations, a significantly worse perinatal outcome for singleton pregnancies following ART compared to pregnancies after natural conception has been reported as well. Most studies only include IVF/ICSI pregnancies; studies describing the perinatal outcome of pregnancies after non-IVF assisted reproduction are scarce. METHODS AND MATERIALS: Population-based cohort study with three exposure groups: a study group of pregnancies (1) after ovarian stimulation (OS), with or without artificial insemination (AI), (2) after IFV or ICSI and (3) a naturally conceived (NC) comparison group. Data from the regional registry of all hospital deliveries in the Dutch-speaking part of Belgium during an 18-years period from January 1993 until December 2010 were used. The perinatal outcome parameters were prematurity, low birth weight, perinatal mortality and morbidity including neonatal intracranial bleeding and need for intubation. Logistic regression analysis was used including mode of conception, female age, foetal sex, parity and year of delivery. RESULTS: Data on 1 079 814 births were studied: 1 039 415 singletons (19 896 IVF/ICSI, 20 469 OS and 999 050 NC) and 39 041 twins (9 353 IVF/ICSI, 4812 OS and 24 876 NC) were available for analysis. IVF/ICSI singletons had a significantly worse outcome when compared to OS and NC for almost all investigated perinatal parameters. Non-IVF/OS singletons were also significantly disadvantaged for prematurity and low birth weight when compared to NC. The outcome of twin pregnancies was similar for the three groups unless only unlike-sex twins were studied separately. Among this subgroup, IVF/ICSI carried a higher risk for low birth weight when compared to NC. OS unlike-sex twins were at increased risk for low birth weight, intra uterine death and perinatal mortality when compared to NC. CONCLUSION: According to our results all ART pregnancies, whether due to IVF/ICSI or non-IVF treatment, have to be considered as risk pregnancies, irrespective of the number of foetuses. LIMITATIONS OF THE STUDY: Although our logistic regression analysis included co-variables with a potential impact on perinatal outcome such as mode of conception, female age, foetal sex, parity and year of delivery, we couldn't correct for other prominent confounders such as the use of fresh or frozen embryos, use of homologous or donor gametes, smoking, obesity, socio-economic status, occupation exposures and pre-existing disease.

Endocrine actions of pesticides measured in the Flemish environment and health studies (FLEHS I and II).

Within the Flemish Environment and Health studies (FLEHS I, 2002-2006, and FLEHS II, 2007-2012), pesticide exposure, hormone levels and degree of sexual maturation were measured in 14-15-year-old adolescents residing in Flanders (Belgium). In FLEHS II, geometric mean concentrations (with 95 % confidence interval (CI)) of 307 (277-341) and 36.5 ng L(-1) (34.0-39.2) were found for p,p'-dichlorophenyldichloroethylene (p,p'-DDE) and hexachlorobenzene (HCB). These values were respectively 26 and 60 % lower than levels in FLEHS I, 5 years earlier. Metabolites of organophosphorus pesticides (OPPs) and of para-dichlorobenzene were measured for the first time in FLEHS II, yielding concentrations of 11.4, 3.27 and 1.57 µg L(-1) for the sum of dimethyl- and diethyl phosphate metabolites and 2,5-dichlorophenol (2,5-DCP), respectively. Data on internal exposure of HCB showed a positive correlation with sexual maturation, testosterone and the aromatase index for boys and with free thyroxine (fT4) and thyroid stimulating hormone (TSH) (both boys and girls). For both p,p'-DDE and HCB, a negative association with sexual development in girls was found. The OPP metabolites were negatively associated with sex hormone levels in the blood of boys and with sexual maturation (both boys and girls). The pesticide metabolite 2,5-DCP was negatively correlated with free T4, while a positive association with TSH was reported (boys and girls). These results show that even exposure to relatively low concentrations of pesticides can have significant influences on hormone levels and the degree of sexual maturation in 14-15-year-old adolescents.

Determination of PCDD/Fs, PBDD/Fs and dioxin-like PCBs in human milk from mothers residing in the rural areas in Flanders, using the CALUX bioassay and GC-HRMS.

Since the CALUX (Chemically Activated LUciferase gene eXpression) bioassay is a fast and inexpensive tool for the determination of dioxin-like compounds in a large number of samples and requires only small sample volumes, the use of this technique in human biomonitoring programs provides a good alternative to GC-HRMS. In this study, a new CALUX method for the separate analysis of PCDD/Fs and dioxin-like PCBs (dl-PCBs) in small amounts of human milk samples with the new sensitive H1L7.5c1 cell line was used to analyze 84 human milk samples, collected from mothers residing in the Flemish rural communities. The geometric mean CALUX-Bioanalytical Equivalent (CALUX-BEQ) values, reported for the 84 mothers from the study area were 10.4 (95% CI: 9.4-11.4) pg CALUX-BEQ per gram lipid or 0.41 (95% CI: 0.37-0.45) pg CALUX-BEQ per gram milk for the PCDD/Fs and 1.73 (1.57-1.91) pg CALUX-BEQ per gram lipid or 0.07 (95% CI: 0.06-0.08) pg CALUX-BEQ per gram milk for the dioxin-like PCBs. Multiple regression analysis showed significant associations between PCDD/Fs and weight change after pregnancy, smoking and consumption of local eggs. One pooled human milk sample was analyzed with both CALUX and GC-HRMS. The ratio of CALUX and GC-HRMS results for this sample were respectively 1.60, 0.58 and 1.23 for the PCDD/Fs, the dl-PCBs and the sum of both fractions, when using the 2005-TEF values. Additionally, also low levels of certain brominated dioxins and furans were detected in the pooled sample with GC-HRMS.

Quantification of PCDD/Fs and dioxin-like PCBs in small amounts of human serum using the sensitive H1L7.5c1 mouse hepatoma cell line: optimization and analysis of human serum samples from adolescents of the Flemish human biomonitoring program FLEHS II.

Since the CALUX (Chemically Activated LUciferase gene eXpression) bioassay is a fast and inexpensive tool for the throughput analysis of dioxin-like compounds in a large number of samples and requires only small sample volumes, the use of this technique in human biomonitoring programs provides a good alternative to GC-HRMS. In this study, a method for the separate analysis of PCDD/Fs and dioxin-like PCBs (dl-PCBs) in human serum with the new sensitive H1L7.5c1 mouse hepatoma cell line was optimized. Sample dilution factors of 5 and 2.4 were selected for routine analysis of respectively the PCDD/Fs and dl-PCBs. The validation studies showed that repeatability and within-lab reproducibility for the quality control (QC) standard were within the in-house criteria. A long-term within-lab reproducibility of 25% for the PCDD/F fraction and 41% for the dl-PCB fraction for the analysis of pooled serum samples, expressed as pg BEQ/g fat, was determined. CALUX recoveries of the spiked procedural blanks were within the acceptable in-house limits of 80-120% for both fractions and the LOQ was 30.3 pg BEQ/g fat for the PCDD/Fs and 14.5 pg BEQ/g fat for the dl-PCBs. The GC-HRMS recovery of a C13-spiked pooled serum sample was between 60 and 90% for all PCDD/F congeners and between 67 and 82% for the non-ortho PCBs. An adequate separation between both fractions was found. The CALUX/GC-HRMS ratio for a pooled serum sample was respectively 2.0 and 1.4 for the PCDD/Fs and the dl-PCBs, indicating the presence of additional AhR active compounds. As expected, a correlation was found between human serum samples analyzed with both the new H1L7.5c1 cell line and the more established H1L6.1c3 cell line. The geometric mean CALUX-BEQ values, reported for the adolescents of the second Flemish Environment and Health Study (FLEHS II) recruited in 2009-2010, were 108 (95% CI: 101-114) pg CALUX-BEQ/g fat for the PCDD/Fs and 32.1 (30.1-34.2) pg CALUX-BEQ/g fat for the dioxin-like PCBs.

Hormone levels and sexual development in Flemish adolescents residing in areas differing in pollution pressure.

In 2002, the Centre for Environment and Health in Flanders, Belgium started a human biomonitoring program. For 1679 adolescents, residing in nine study areas with differing pollution pressure, hormone levels and the degree of sexual maturation were measured. Possible confounding effects of lifestyle and personal characteristics were taken into account. Participants from the nine different study areas had significantly different levels of sex hormones (total and free testosterone, oestradiol, aromatase, luteinizing hormone) and the thyroid hormone free triiodothyronine, after correction for confounders. Significantly higher hormone concentrations were measured in samples from participants residing in the area around the waste incinerators, while significantly lower values were found in participants residing in the Albert Canal zone with chemical industry. Sexual maturation of boys as well as girls tended to be somewhat slower in the industrial city of Antwerp and in the Antwerp harbour compared to the other areas in Flanders. Even within the same study area, significant differences in hormone levels could be observed between sub-areas. Data on the internal exposure of the same adolescents to lead, cadmium, PCBs, p,p'-DDE, HCB, 1-hydroxypyrene and t,t'-muconic acid have already been published. The observed differences in hormone levels and in sexual maturation could however only in part be explained by the measured differences in internal exposure to pollutants, suggesting that also other pollutants and other factors that vary in function of the area of residence could play a role. Nevertheless, our results also suggest that local (environmental) factors, acting within a short distance, might influence the measured hormone levels and degree of sexual maturation.

Previous intravenous substance use and outcome of liver transplantation in patients with chronic hepatitis C infection.

BACKGROUND: End-stage liver disease due to hepatitis C viral (HCV) infection is the most common reason for liver transplantation. One of the major risk factors for infection with HCV is intravenous drug use (IVDU). The pretransplantation characteristics and outcome of liver transplantation in patients with chronic hepatitis C (CHC) infected after IVDU are poorly known. METHODS: We performed a retrospective cohort study in patients with CHC who underwent liver transplantation between 1998 and 2002 in Belgium. Seven patients with and 60 patients without a history of IVDU were compared. RESULTS: Patients with CHC infected after IVDU were primarily men, significantly younger, and affected more by genotype 2 or 3. There was no relapse in substance use. No patients required a second transplantation or developed surgical complications. Progression to fibrosis in the posttransplantation period seemed to be slower. Graft and patient survival, and compliance were similar in both groups. CONCLUSIONS: Compared with patients in the non-IVDU group, patients with CHC infected after IVDU in complete remission have the same compliance, and patient and graft survival after liver transplantation. Therefore, patients with IVDU should not be excluded for liver transplantation because of HCV-induced cirrhosis.

Internal exposure to pollutants measured in blood and urine of Flemish adolescents in function of area of residence.

The Centre for Environment and Health in Flanders, the Northern part of Belgium, started a biomonitoring program on adolescents in 2003. 1679 adolescents residing in nine areas with different patterns of pollution participated in the study. Possible confounding effects of lifestyle and personal characteristics were taken into account. The geometric mean levels of cadmium and lead in whole blood amounted to 0.36 and 21.7 microg l(-1), those of PCBs, DDE and HCB in serum to 68, 94 and 20.9 ng g(-1) fat, and those of 1-hydroxypyrene and t,t'-muconic acid in urine to 88 ng g(-1) creatinine and 72 microg g(-1) creatinine. Significant regional differences in internal lead, cadmium, PCBs, DDE and HCB exposure were observed in function of area of residence, even after adjustment for age, sex, smoking (and body mass index for the chlorinated compounds). Compared to a reference mean, internal exposure was significantly higher in one or more of the areas: Cd and Pb in the Antwerp agglomeration, Cd in the Antwerp harbour, PCBs in the Ghent agglomeration, PCBs, DDE and HCB in the Ghent harbour, Cd, PCBs, DDE and HCB in the rural area, DDE in Olen and in the Albert canal areas. Adolescents living in an area with intensive fruit cultivation (showing overall the lowest values) and, surprisingly, in areas around household waste incinerators (average of six areas), had no significantly increased internal exposures. Subjects from separate areas around waste incinerators showed significant differences in body load of various environmental contaminants.

The investigation of a geographical cluster of bladder cancer.

Previous analyses of the Limburg Cancer registry (LIKAR) indicated the existence of a geographical cluster of bladder cancer incidence, particularly transitional cell carcinomas, amongst males in the surrounding area of the Belgian cities Hasselt and Alken. In subsequent ecologic analyses no risk factors were identified which could explain the existence of this cluster. Therefore, an epidemiological case-control study has been performed in the province of Limburg to explore the possible determinants of the cluster. The following cluster determinants were investigated: socio-demographic characteristics, life style factors, occupational and environmental exposures, and genetic predisposition. A weight was assigned to all the study subjects. Secondly, we used unconditional logistic regression to calculate crude odd ratios (ORs) and 95% confidence intervals (CIs) for each source of exposure and bladder cancer. Thirdly, we used a multivariate logistic regression analysis which included all the parameters found to be significant at the 0.1 significance level in the univariate analysis. Although some of the specific odds ratios decreased compared with the crude results, the overall excess did not change specifically. In conclusion, we were not able to identify a clear-cut explanation for the existence of the geographical cluster. We therefore recommend an increased surveillance of bladder cancer incidence for 3 to 5 years. If the "excess" of cancer cases has occurred due to random variation, the rate will return to the "expected" range in the next years. If the rate remains elevated, further studies may need to be performed using investigative tools that are not available currently.

Pesticides and mortality from hormone-dependent cancers.

Endocrine-disrupting chemicals are considered to be a possible cause of hormone-dependent cancers. In areas of high exposure to pesticides, people are concerned about the long lasting toxicity of pesticides, some of which are possibly hormonally active. We collected for each Belgian municipality (n = 589) the latest mortality statistics from breast and prostate cancer (period 1985-1994) and the latest data on crops and pesticides (1998). In addition, data on possible confounders such as population density, degree of urbanization, industrial activity and the presence of an incinerator were collected as well. The data were analysed with spatial statistics that takes into account the spatial nature of the data. There is a large variation in crops and pesticide exposure among the municipalities, the highest exposure being seen in the fruit production area. Apart from use of defoliants and potato cultivation, no consistent correlation was detected between crops, pesticides and mortality from breast and prostate cancer. Our data cannot support the hypothesis of a relationship between total and class-related pesticide use and breast and prostate cancer mortality. However, the increased mortality due to breast cancer and to a lesser extent due to prostate cancer in traditional potato-growing areas needs attention and more research.

Effects of soft drink and table beer consumption on insulin response in normal teenagers and carbohydrate drink in youngsters.

There is ample evidence that breast cancer susceptibility is induced during the developmental stages of the human breast where, in a manner related to sex-steroid hormones, insulin plays an important role. In turn, nutrition might be implicated. Regular soft drinks and table beer, both carbohydrate-containing drinks, are candidates affecting insulin concentrations. Eleven teenagers, between the ages of 13 and 17 years, consumed a soft drink and a table beer in a crossover study. The blood levels of insulin and glucose were related to anthropomorphometric and endocrine factors. In contrast to table beer, consumption of regular soft drinks induced a fast and dramatic increase in both glucose and insulin concentration within a maximum 1 hour after consumption. The insulin response was linearly correlated to the body mass index (BMI). Children with a small increase in BMI are highly sensitive to regular soft drinks with regard to glucose and insulin response. The finding suggests a vicious circle of high caloric drinks, increase in BMI and insulin response. It is one of the nutritional pathways which might affect susceptibility for breast cancer in youngsters. Table beer, a drink with fermented sugars, does not share these effects on carbohydrate metabolism.