Development of a Dutch Version of the Sydney Swallow Questionnaire: Assessing Oropharyngeal Dysphagia Severity in Dutch-Speaking Populations.

Aims: The oropharyngeal dysphagia (OD) poses substantial health risks and affects quality of life. Patient-reported outcome measures (PROMs) are gaining prominence for their crucial role in early detection and adapting rehabilitation and management decisions. This highlights the need for culturally pertinent versions in different languages, especially when addressing conditions like OD. This study aimed to translate, culturally adapt, and assess the test-retest reliability of the Sydney Swallow Questionnaire (SSQ), a PROM designed to detect the risk of OD, for Dutch-speaking populations. Materials and Methods: The SSQ was translated and adapted based on Beaton's guidelines. Validity and test-retest reliability were assessed in 100 healthy participants, with a subset of 30 participants assessed over a 15-day interval. Intra-class correlation coefficient (ICC) values were calculated to determine test-retest reliability. Results: The SSQ-Dutch was well received and well understood, with a median total score of 65.5/1700. Notably, 95% of participants scored below the established dysphagia risk cut-off, consistent with previous validations. The 15-day interval ICC for the SSQ-Dutch total scores was 0.82 (CI 95%: 0.66-0.91), indicating good reliability. While most questions had moderate-to-good reliability, five showed slightly lower ICC. Conclusion: The SSQ-Dutch emerges as a validated and reliable tool for assessing OD risk in Dutch-speaking individuals. Future studies should evaluate its efficacy in symptomatic populations and consider cultural variations in Dutch-speaking regions. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-024-04484-3.

Challenges in modeling the Agility multileaf collimator in treatment planning systems and current needs for improvement.

BACKGROUND: The Agility multileaf collimator (MLC) mounted in Elekta linear accelerators features some unique design characteristics, such as large leaf thickness, eccentric curvature at the leaf tip, and defocused leaf sides ('tilting'). These characteristics offer several advantages but modeling them in treatment planning systems (TPSs) is challenging. PURPOSE: The goals of this study were to investigate the challenges faced when modeling the Agility in two commercial TPSs (Monaco and RayStation) and to explore how the implemented MLC models could be improved in the future. METHODS: Four linear accelerators equipped with the Agility, located at different centers, were used for the study. Three centers use the RayStation TPS and the other one uses Monaco. For comparison purposes, data from four Varian linear accelerators with the Millennium 120 MLC were also included. Average doses measured with asynchronous sweeping gap tests were used to characterize and compare the characteristics of the Millennium and the Agility MLCs and to assess the MLC model in the TPSs. The FOURL test included in the ExpressQA package, provided by Elekta, was also used to evaluate the tongue-and-groove with radiochromic films. Finally, raytracing was used to investigate the impact of the MLC geometry and to understand the results obtained for each MLC. RESULTS: The geometry of the Agility produces dosimetric effects associated with the rounded leaf end up to a distance 20 mm away from the leaf tip end measured at the isocenter plane. This affects the tongue-and-groove shadowing, which progressively increases along the distance to the tip end. The RayStation and Monaco TPSs did not account for this effect, which made trade-offs in the MLC parameters necessary and greatly varied the final MLC parameters used by different centers. Raytracing showed that these challenging leaf tip effects were directly related to the MLC geometry and that the characteristics mainly responsible for the large leaf tip effects of the Agility were its tilting design and its small source-to-collimator distance. CONCLUSIONS: The MLC models implemented in RayStation and Monaco could not accurately reproduce the leaf tip effects for the Agility. Therefore, trade-offs are needed and the optimal MLC parameters are dependent on the specific characteristics of treatment plans. Refining the MLC models for the Agility to better approximate the measured leaf tip and tongue-and-groove effects would extend the validity of the MLC model, reduce the variability in the MLC parameters used by the community, and facilitate the standardization of the MLC configuration process.

Improved cone-beam computed tomography in supine and prone breast radiotherapy. Surface reconstruction, radiation exposure, and clinical workflow.

BACKGROUND AND PURPOSE: Cone-beam computerized tomography (CBCT) enables three-dimensional information of the scanned region and provides soft tissue images with good spatial resolution. Our aim was to optimize image acquisition settings for prone and supine breast radiotherapy with respect to contour accuracy, clinical practicalities, and radiation dose. PATIENTS AND METHODS: CBCT images were acquired for both prone and supine anthropomorphic phantoms and a female cadaver in supine and prone set-up. CBCT protocols were investigated by altering the tube current, exposure time, range of projection views, field of view (FOV), and starting angle. For clinical practicalities, the frequency of the use of an offset CBCT isocenter was evaluated at 558 205°-CBCTs (37 patients; 13 prone and 24 supine) and 1272 360°-CBCTs (102 patients; 13 prone and 89 supine). RESULTS: Prone and supine breast CBCT images acquired with a bowtie filter, a small FOV, a range of projection views equaling 180°, a tube current of 20 mA and an exposure time of 32 ms, demonstrated adequate contour accuracy and an elimination of the offset CBCT isocenter procedure, while this occurred in 40.7 % for the old full-rotation protocol. Furthermore a 4.3-fold dose reduction was observed for the Computed Tomography Dose Index (CTDIw) compared to the preset Chest M20 protocol. CONCLUSION: The established 180° protocol demonstrated acceptable contour accuracy, eliminated the CBCT isocenter offset procedure and reduced patient radiation exposure.

Amyotrophic lateral sclerosis and excitotoxicity: from pathological mechanism to therapeutic target.

Glutamate-induced excitotoxicity is responsible for neuronal death in acute neurological conditions as well as in chronic neurodegeneration. In this review, we give an overview of the contribution of excitotoxicity in the pathogenesis of amyotrophic lateral sclerosis (ALS). The selective motor neuron death that is the hallmark of this neurodegenerative disease seems to be related to a number of intrinsic characteristics of these neurons. Most of these characteristics relate to calcium entry and calcium handling in the motor neurons as intracellular free calcium concentrations increase quickly due to a high glutamate-induced calcium influx in combination with a low calcium buffering capacity. The high calcium influx is because of the presence of GluR2 lacking, calcium-permeable AMPA receptors while a low expression of calcium binding proteins explains the low calcium buffering capacity. In the absence of these proteins, mitochondria play an important role to remove calcium from the cytoplasm. While all of these characteristics make at least a subpopulation of motor neurons intrinsically very prone to AMPA receptor mediated excitotoxicity, this vulnerability is further increased by the disease process. Mutated genes as well as unknown factors do not only influence the intrinsic characteristics of the motor neurons, but also the properties of the surrounding astrocytes. In conclusion, excitotoxicity remains an intriguing pathological pathway that could not only explain the selectivity of the motor neuron death but also the role of surrounding non-neuronal cells in ALS. In addition, excitotoxicity is also an interesting drug-able target as indicated by the only FDA-approved drug, riluzole, as well as by a number of ongoing clinical trials.

A large-scale multicentre study of patient skin doses in interventional cardiology: dose-area product action levels and dose reference levels.

For 318 patients in 8 different Belgian hospitals, the entire skin-dose distribution was mapped using a grid of 70 thermoluminescence dosimeters per patient, allowing an accurate determination of the maximum skin dose (MSD). Dose-area product (DAP) values, exposure parameters and geometry, together with procedure, patient and cardiologist characteristics, were also registered. Procedures were divided into two groups: diagnostic procedures (coronary angiography) and therapeutic procedures (dilatation, stent, combined procedures (e.g. coronary angiography + dilatation + stent)). The mean value of the MSD was 0.310 Gy for diagnostic and 0.699 Gy for therapeutic procedures. The most critical projection for receiving the MSD is the LAO90 (left anterior oblique) geometry. In 3% of cases, the MSD exceeded the 2 Gy dose threshold for deterministic effects. Action levels in terms of DAP values as the basis for a strategy for follow-up of patients for deterministic radiation skin effects were derived from measured MSD and cumulative DAP values. Two DAP action levels are proposed. A first DAP action level of 125 Gy cm(2) corresponding to the dose threshold of 2 Gy would imply an optional radiopathological follow-up depending on the cardiologist's decision. A second DAP action level of 250 Gy cm(2) corresponding to the 3 Gy skin dose would imply a systematic follow-up. Dose reference levels - 71.3 Gy cm(2) for diagnostic and 106.0 Gy cm(2) for therapeutic procedures - were derived from the 75 percentile of the DAP distributions. As a conclusion, we propose that total DAP is registered in patient's record file, as it can serve to improve the follow-up of patients for radiation-induced skin injuries.

Does digital flat detector technology tip the scale towards better image quality or reduced patient dose in interventional cardiology?

As dynamic flat-panel detectors (FD) are introduced in interventional cardiology (IC), the relation between patient dose and image quality (IQ) needs to be reconsidered for this type of image receptor. On one hand this study investigates IQ of a FD system by means of a threshold contrast-detail analysis and compares it to an image intensifier (II) system on a similar X-ray setup. On the other hand patient dose for coronary angiography (CA) procedures on both systems is compared by Dose-Area Product (DAP)-registration of a patient population. The comparative IQ study was performed for a range of entrance dose rates (EDR) covering the fluoroscopy and cinegraphy working mode. In addition the IQ investigation was extended to a similar study under automatic brightness control (ABC). As well the systematic study of IQ as a function of EDR as the study performed under ABC point to a better IQ for FD in cinegraphy mode and no difference between both systems in fluoroscopy mode. The patient population study resulted in mean DAP values of 31Gycm(2) (II system) and 33Gycm(2) (FD system) (p=0.68) for CA procedures. As well total DAP as contributions of fluoroscopy and cinegraphy on both systems are not significantly different. To conclude, we could state that profit was taken from the intrinsic better performance of the FD for cinegraphy mode in producing higher quality images in this mode but without any effect on patient dose for CA procedures.

Interventional cardiovascular procedures in Belgium: effective dose and conversion factors.

Effective dose (E), representing the risk of late radiation-induced effects, can be estimated by the use of conversion factors (CF), converting direct measurable quantities such as dose-area-product into E. Eight Belgian hospitals participated in the study with a total number of 318 procedures. E-values, calculated with PCXMC, were compared for the different hospitals for diagnostic and therapeutic procedures separately. E-values varied significantly depending on the hospital where the procedure was performed (P < 0.001), on filtration insertion (P < 0.001), on whether a centre is a training centre or not, the dose conscious action of the cardiologists and the complexity of the procedure (P < 0.001). Hospital-specific CF were calculated. An average CF of 0.185 mSv Gycm(-2) was obtained with a satisfactory correlation (r = 0.966, P < 0.001). The differences in CF between hospitals were due to, a large extent, the availability of additional filtration in cinegraphy mode (P < 0.001) and not to the differences in irradiation geometries in the clinical protocol of the interventional procedures.

A large-scale multicentre study in Belgium of dose area product values and effective doses in interventional cardiology using contemporary X-ray equipment.

In this paper, a large-scale multicentre patient dose study performed in eight Belgian interventional cardiology departments is presented. Effective dose (E) was calculated based on a detailed dose-area product (DAP)-registration during each procedure and by using conversion coefficients generated by the Monte Carlo-based computer program PCXMC. Conversion coefficients were found to be 0.177 mSv Gycm(-2) for systems that do not use any additional copper filtration in cineradiography and 0.207 mSv Gycm(-2) for systems that use additional copper filtration in cineradiography. Mean E values of 9.6 and 15.3 mSv for diagnostic and therapeutic procedures, respectively, were obtained. DAP distributions were investigated in order to derive dose reference levels: 71 and 106 Gycm2 for diagnostic and therapeutic procedures, respectively, are proposed. Significant differences were observed in DAP distributions taking into account whether additional copper filtration was used in the cineradiography mode. Apart from the skin, the organs most at risk are lungs and heart. The probability of fatal cancer for the studied population amounted to 1.1x10(-4) and 2.1x10(-4) for diagnostic and therapeutic procedures, respectively, for the age distribution of the patients considered in this multicentre study.

The role of excitotoxicity in the pathogenesis of amyotrophic lateral sclerosis.

Unfortunately and despite all efforts, amyotrophic lateral sclerosis (ALS) remains an incurable neurodegenerative disorder characterized by the progressive and selective death of motor neurons. The cause of this process is mostly unknown, but evidence is available that excitotoxicity plays an important role. In this review, we will give an overview of the arguments in favor of the involvement of excitotoxicity in ALS. The most important one is that the only drug proven to slow the disease process in humans, riluzole, has anti-excitotoxic properties. Moreover, consumption of excitotoxins can give rise to selective motor neuron death, indicating that motor neurons are extremely sensitive to excessive stimulation of glutamate receptors. We will summarize the intrinsic properties of motor neurons that could render these cells particularly sensitive to excitotoxicity. Most of these characteristics relate to the way motor neurons handle Ca(2+), as they combine two exceptional characteristics: a low Ca(2+)-buffering capacity and a high number of Ca(2+)-permeable AMPA receptors. These properties most likely are essential to perform their normal function, but under pathological conditions they could become responsible for the selective death of motor neurons. In order to achieve this worst-case scenario, additional factors/mechanisms could be required. In 1 to 2% of the ALS patients, mutations in the SOD1 gene could shift the balance from normal motor neuron excitation to excitotoxicity by decreasing glutamate uptake in the surrounding astrocytes and/or by interfering with mitochondrial function. We will discuss point by point these different pathogenic mechanisms that could give rise to classical and/or slow excitotoxicity leading to selective motor neuron death.

[Fatal neonatal respiratory distress in Niemann-Pick C2 and prenatal diagnosis with mutations in gene HE1/NPC2]. / Forme respiratoire néonatale létale de la maladie de Niemann-Pick C2 et diagnostic anténatal par l'étude des mutations du gène HE1/NPC2.

UNLABELLED: We report the fifth case of neonatal form of type C2 (NP-C2) Niemann-Pick disease with early and fatal respiratory distress. Eleven families presenting such cases are known to date in the world. Since December 2000, isolation of the underlying gene HE1/NPC2 and its mutations has allowed major advances in diagnosis. CASE REPORT: Elisa was born in May 2000. NP-C2 disease was associated with severe respiratory distress leading to death at the age of four months. On the next pregnancy in September 2000, prenatal diagnosis was performed by means of biological tests that required four weeks response time. In December 2000, isolation of the HE1/NPC2 gene located to 14q24.3 and of some of its mutations allowed to characterize the patient as being homozygote for the nonsense mutation E20X. On the the two next pregnancies, prenatal diagnosis was performed at 12 SA, in 48 hours, by the means of mutation analysis. The last fetus was heterozygote for the mutation E20X, allowing the birth at term of a healthy male newborn baby. CONCLUSION: Niemann-Pick type C disease is a rare lysosomal lipid storage disease with severe prognosis. It is characterized by abnormalities of intracellular transport of endocytosed cholesterol. Diagnosis relies on biological tests that require cultured cells. Genetic heterogeneity defines two different genetic complementation groups C1 and C2. Severe and early respiratory distress is more likely to be associated with the rare type C2. Since December 2000, after identification of the disease-causing mutations in the proband, mutation analysis of gene HE1/NPC2 on direct chorionic villus samples allows early and fast (48 hours) prenatal diagnosis.

The use of ursodeoxycholic acid in patients with primary biliary cirrhosis: sense or nonsense.

Ursodeoxycholic acid is the most widely evaluated drug for the treatment of primary biliary cirrhosis. The results of the first randomized controlled trials are very discordant in terms of survival benefit. This, however, can be explained by differences in methodology and insufficiently long period of treatment and follow-up. It has clearly been demonstrated that serum bilirubin levels and histological parameters such as piecemeal necrosis and fibrosis are validated predictors of prognosis in PBC. We re-analyzed the already published data using these parameters as surrogate endpoints. This analysis reveals that there is a significant positive effect of treatment of PBC with UDCA on serum bilirubin levels as well as on the progression of piecemeal necrosis and fibrosis. We therefore conclude that UDCA has a positive effect on the prognosis of PBC and can slow down the progression to end stage liver disease.

Laparoscopic sacrocolpopexy, hysterectomy, and burch colposuspension: feasibility and short-term complications of 77 procedures.

OBJECTIVE: To report our first cases of laparoscopic sacropexy and assess the feasibility and short-term complications. METHODS: We retrospectively studied 77 laparoscopic sacral colpopexies performed from June 1996 to May 1998. Suspension was reinforced with 2 strips of synthetic mesh. Five patients had previously undergone hysterectomy, and 4 others had experienced failure of surgery for prolapse of the uterus. RESULTS: Laparoscopy was performed in 83 women with symptomatic prolapse of the uterus. Six cases required conversion to laparotomy because of technical difficulties. All of the remaining 77 patients underwent laparoscopic sacropexy that included anterior and posterior mesh reinforcement. Subtotal laparoscopic hysterectomy was performed in 60 cases, laparoscopic Burch colposuspension in 74, and levator myorrhaphy via a vaginal approach in 55. Operative time decreased from 292 to 180 minutes as experience was gained. The main operative complications were 1 rectal and 2 bladder injuries. Three patients required reoperations for hematoma or hemorrhage. One patient complained of chronic inflammation of the cervix, and another experienced rejection of the posterior mesh 6 months after the operation. Mean follow-up was 343 days. Three other patients required reoperation, 1 for a third-degree cystocele and 2 for recurrent stress incontinence. CONCLUSION: Laparoscopic sacrocolpopexy is feasible. Operative time and postoperative complications are related to the surgeon's experience but remain comparable to those noted in laparotomy. Long-term assessment is required to confirm the results of this procedure.

[Cytological history of 148 women presenting with invasive cervical cancer]. / Histoire du suivi cytologique de 148 femmes atteintes d'un cancer invasif du col utérin.

OBJECTIVES: The aim of this study was to analyse the cytological history of women presenting with invasive cervical cancer. MATERIAL AND METHODS: Retrospective study of 148 patients treated for invasive cervical cancer in three hospitals of the North Pas de Calais in France. RESULTS: The average age of patients was 49 (26-86). Squamous carcinomas represented 81% of cases (120/148), adenocarcinomas 17% (25/148) and adenosquamous carcinomas 2% (3/148). 36.5% of patients (54/148) had never had a Pap smear. 34.5% (51/148) had had an occasional Pap smear (the last one dated of more than three years). 8.1% (12/148) were lost for follow up after a positive Pap smear. 3.4% (5/148) were treated for cervical dysplasia less than three years before the diagnosis of the cervical cancer. 17.5% (26/148) had had a Pap smear reported as negative less than three years before the diagnosis of the cervical cancer. In this last group, squamous carcinomas represented 57.7% of cases (15/26), adenocarcinomas 38.5% (10/26) and adenosquamous carcinomas 3.8% (1/26). 18 Pap smears of 26 reported as negative less than three years before the diagnosis of the cancer were reviewed. These Pap smears came from 11 patients presenting with squamous carcinoma and seven other presenting with adenocarcinoma. After review, 15 Pap smears were reported as false negatives and two as true negatives. The review was not possible in one case. CONCLUSION: In this study, the failures of cervical cancer screening were essentially attributed to the lack or the insufficiency of screening and the existence of false negatives of the cytology.

[Laparoscopic sacral colpopexy: short-term results and complications in 83 patients]. / Promontofixation coelioscopique: résultats à court terme et complications chez 83 patientes.

We retrospectively studied 77 laparoscopic sacral colpopexies performed from June 1996 to May 1998. Suspension was reinforced with two strips of synthetic mesh. Five patients had previously undergone hysterectomy and 4 others had experienced failure of surgery for prolapse of the uterus. Laparoscopy was performed in 83 women with symptomatic prolapse of the uterus. Six cases required conversion to laparotomy because of technical difficulties. All other 77 patients underwent laparoscopic sacropexy using anterior and posterior mesh reinforcement. Subtotal laparoscopic hysterectomy was associated in 60 cases, laparoscopic Burch colposuspension in 74 and levator myorraphy using the vaginal approach in 55. Operative time decreased from 292 to 180 minutes as the surgeon gained experience. The main operative complications were one rectal and two bladder injuries. Three patients required reoperations for haematoma or hemorrhage. One patient complained of chronic inflammation of the cervix and another experienced rejection of the posterior mesh 6 months after the operation. Mean follow up was 343 days. Three other patients required reoperation: one for a 3(rd) degree cystocele and two for recurrent stress incontinence. The conclusion of this study is that laparoscopic sacrocolpopexy is feasible. Operative time and postoperative complications are related to the surgeon's experience but remain comparable to those noted in laparotomy. Long term assessment is required to confirm the results of this procedure.

Prenatal diagnosis of a constitutional interstitial deletion of chromosome 5 (q15q31.1) presenting with features of congenital contractural arachnodactyly.

Prenatal diagnosis of a constitutional interstitial deletion of chromosome 5 (q15q31.1) in a 30-year-old woman is reported. At 21 weeks of pregnancy, routine fetal ultrasounds showed the presence of apparently isolated bilateral club feet. Fetal karyotyping documented an interstitial deletion of the long arm of chromosome 5: 46,XX,del(5) (q15q31) in all 50 analyzed metaphases. Because such deletion is associated with severe psychomotor retardation, the pregnancy was terminated. Postmortem karyotyping of skin fibroblasts confirmed the presence of this interstitial de novo deletion in all mitoses. The breakpoints on 5q were analyzed by fluorescent in situ hybridization and were localized at 5q15 and q31.1. This case illustrates the importance of fetal karyotyping in cases of isolated club feet. At autopsy, the fetus presented had minor anomalies and contractures of knee and hip joints. These clinical findings could fit the diagnosis of congenital contractural arachnodactyly (CCA) or Beals syndrome. CCA is caused by a defect in the fibrillin-2 (FBN2) gene. This gene was previously mapped on 5q23-31. Our molecular studies of both parents and the fetus, using an intragenic polymorphic GT repeat, showed that the FBN2 gene was deleted in the fetus and that the de novo interstitial deletion occurred on the paternally inherited chromosome 5. Thus, CCA may be caused by a loss of function of the FBN2 gene. Clinical findings in this fetus and those of other described cases with interstitial 5q deletions are reviewed, and similarities with CCA are stressed.

Alkaline phosphatase activities in human amniotic fluid, chromatographic separation of the foetal intestinal component.

Hydrophilic gel permeation chromatography of 14-36 wk human amniotic fluid on Fractogel columns divides the total alkaline phosphatase (AP) activity in a higher and a lower mol wt zones. Differential inhibition testing, isoelectric focusing, cellulose acetate, agarose and polyacrylamide gel electrophoreses before and after neuraminidase treatment show the higher mol wt zone to be homogeneous and to be made of the higher mol wt foetal intestinal isoenzyme form whereas the lower mol wt zone represents an unresolved mixture of hepatic, placental and lower mol wt foetal intestinal isoenzymes. In the early stages of pregnancy, the activity associated with the higher mol wt zone outweighs by far that of the lower mol wt zone; however from the 24 th week one notes a steady increase in the relative magnitude of this second zone until at the end of the gestation period both zones assume near equal importance albeit within a lower total AP activity. Satisfactory quantitation of the higher mol wt foetal intestinal isoenzyme form in one ml amniotic fluid can be attained after a 3-h chromatography run using p-nitrophenylphosphate as substrate.

Alkaline phosphatase isoenzyme pattern in human amniotic fluid is dependent on the level of total activity. Implications in cystic fibrosis diagnosis.

Alkaline phosphatase activities have been examined in 500 consecutive human amniotic fluids obtained at diagnostic paracentesis between 14 and 38 wk of gestation. They were found to have a non-Gaussian, positively skewed distribution, independent of the protein concentrations. Residual activities after heat treatment or in presence of phenylalanine and levamisole allow evaluation of the placental, hepatic and intestinal isoenzyme components. It is shown that the contribution of the intestinal isoenzyme to the total activity is a linear function of the latter. This fact should be taken into account in the enzymatic diagnosis of cystic fibrosis as it is apparent that the part contributed by the intestinal isoenzyme is predictably smaller when the level of total activity is low.