MRI segmentation of tooth tissue in age prediction of sub-adults - a new method for combining data from the 1st, 2nd, and 3rd molars.

PURPOSE: We aimed to establish a model combining MRI volume measurements from the 1st, 2nd and 3rd molars for age prediction in sub-adults and compare the age prediction performance of different combinations of all three molars, internally in the study cohort. MATERIAL AND METHOD: We examined 99 volunteers using a 1.5 T MR scanner with a customized high-resolution single T2 sequence. Segmentation was performed using SliceOmatic (Tomovision©). Age prediction was based on the tooth tissue ratio (high signal soft tissue + low signal soft tissue)/total. The model included three correlation parameters to account for statistical dependence between the molars. Age prediction performance of different combinations of teeth for the three molars was assessed using interquartile range (IQR). RESULTS: We included data from the 1st molars from 87 participants (F/M 59/28), 2nd molars from 93 (F/M 60/33) and 3rd molars from 67 (F/M 45/22). The age range was 14-24 years with a median age of 18 years. The model with the best age prediction performance (smallest IQR) was 46-47-18 (lower right 1st and 2nd and upper right 3rd molar) in males. The estimated correlation between the different molars was 0.620 (46 vs. 47), 0.430 (46 vs. 18), and 0.598 (47 vs. 18). IQR was the smallest in tooth combinations including a 3rd molar. CONCLUSION: We have established a model for combining tissue volume measurements from the 1st, 2nd and 3rd molars for age prediction in sub-adults. The prediction performance was mostly driven by the 3rd molars. All combinations involving the 3rd molar performed well.

Prediction of Age Older than 18 Years in Sub-adults by MRI Segmentation of 1st and 2nd Molars.

PURPOSE: To investigate prediction of age older than 18 years in sub-adults using tooth tissue volumes from MRI segmentation of the entire 1st and 2nd molars, and to establish a model for combining information from two different molars. MATERIALS AND METHODS: We acquired T2 weighted MRIs of 99 volunteers with a 1.5-T scanner. Segmentation was performed using SliceOmatic (Tomovision©). Linear regression was used to analyse the association between mathematical transformation outcomes of tissue volumes, age, and sex. Performance of different outcomes and tooth combinations were assessed based on the p-value of the age variable, common, or separate for each sex, depending on the selected model. The predictive probability of being older than 18 years was obtained by a Bayesian approach using information from the 1st and 2nd molars both separately and combined. RESULTS: 1st molars from 87 participants, and 2nd molars from 93 participants were included. The age range was 14-24 years with a median age of 18 years. The transformation outcome (high signal soft tissue + low signal soft tissue)/total had the strongest statistical association with age for the lower right 1st (p= 7.1*10-4 for males) and 2nd molar (p=9.44×10-7 for males and p=7.4×10-10 for females). Combining the lower right 1st and 2nd molar in males did not increase the prediction performance compared to using the best tooth alone. CONCLUSION: MRI segmentation of the lower right 1st and 2nd molar might prove useful in the prediction of age older than 18 years in sub-adults. We provided a statistical framework to combine the information from two molars.

Downgrading of referrals to breast cancer patient pathway. / Nedprioritering av henvisninger til pakkeforløp for brystkreft.

BACKGROUND: The purpose of the study was to investigate whether the downgrading of external referrals to breast cancer patient pathways was clinically justifiable and led to a more correct prioritisation of patients who are referred to the specialist health service. MATERIAL AND METHOD: The study included 214 external referrals to breast cancer patient pathways at the Breast Screening Centre, Oslo University Hospital, which were downgraded in 2020 since they did not meet the national criteria. The information obtained from electronic patient records included age, district of Oslo, name of referring doctor, outcome after investigation and treatment, as well as recommended timeframe for initiating the investigation. The quality of the referrals was also assessed. RESULTS: A total of 3 % (7/214) of patients were diagnosed with breast cancer. Five were in the age group 40-50 years (9 %, 5/56), one was over the age of 50 years (1/31) and one was in the age group 35-40 years (1/38). None were below the age of 35 years. A total of 95 doctors had their referrals downgraded. INTERPRETATION: The study indicated that the downgrading of referrals to breast cancer patient pathways led to a more correct prioritisation of patients who are referred to the specialist health service. The results indicated that the downgrading was clinically justifiable for the age groups under 35 years and over 50 years, but that caution must be exercised when downgrading referrals in the age group 40-50 years.

Age prediction in sub-adults based on MRI segmentation of 3rd molar tissue volumes.

PURPOSE: Our aim was to investigate tissue volumes measured by MRI segmentation of the entire 3rd molar for prediction of a sub-adult being older than 18 years. MATERIAL AND METHOD: We used a 1.5-T MR scanner with a customized high-resolution single T2 sequence acquisition with 0.37 mm iso-voxels. Two dental cotton rolls drawn with water stabilized the bite and delineated teeth from oral air. Segmentation of the different tooth tissue volumes was performed using SliceOmatic (Tomovision©). Linear regression was used to analyze the association between mathematical transformation outcomes of the tissue volumes, age, and sex. Performance of different transformation outcomes and tooth combinations were assessed based on the p value of the age variable, combined or separated for each sex depending on the selected model. The predictive probability of being older than 18 years was obtained by a Bayesian approach. RESULTS: We included 67 volunteers (F/M: 45/22), range 14-24 years, median age 18 years. The transformation outcome (pulp + predentine)/total volume for upper 3rd molars had the strongest association with age (p = 3.4 × 10-9). CONCLUSION: MRI segmentation of tooth tissue volumes might prove useful in the prediction of age older than 18 years in sub-adults.

Fat infiltration in the thigh muscles is associated with symptomatic spinal stenosis and reduced physical functioning in adults with achondroplasia.

BACKGROUND: Symptomatic spinal stenosis is a prevalent complication in adults with achondroplasia. Increased muscle fat infiltration (MFI) and reduced thigh muscle volumes have also been reported, but the pathophysiology is poorly understood. We explored whether the increased MFI and reduced thigh muscle volumes were associated with the presence of symptomatic spinal stenosis and physical functioning. METHODS: MFI and thigh muscle volumes were assessed by MRI in 40 adults with achondroplasia, and compared to 80 average-statured controls, matched for BMI, gender, and age. In achondroplasia participants, the six-minute walk-test (6MWT), the 30-s sit-to-stand test (30sSTS), and a questionnaire (the IPAQ) assessed physical functioning. RESULTS: Symptomatic spinal stenosis was present in 25 of the participants (the stenosis group), while 15 did not have stenosis (the non-stenosis group). In the stenosis group, 84% (21/25) had undergone at least one spinal decompression surgery. The stenosis group had significantly higher MFI than the non-stenosis group, with an age-, gender and BMI-adjusted difference in total MFI of 3.3 percentage points (pp) (95% confidence interval [CI] 0.04 to 6.3 pp; p = 0.03). Compared to matched controls, the mean age-adjusted difference was 3.3 pp (95% CI 1.7 to 4.9 pp; p < 0.01). The non-stenosis group had MFI similar to controls (age-adjusted difference - 0.9 pp, 95% CI - 3.4 to 1.8 pp; p = 0.51). MFI was strongly correlated with the 6MWT (r = - 0.81, - 0.83, and - 0.86; all p-values < 0.01), and moderately correlated with the 30sSTS (r = - 0.56, - 0.57, and - 0.59; all p-values < 0.01). There were no significant differences in muscle volumes or physical activity level between the stenosis group and the non-stenosis group. CONCLUSION: Increased MFI in the thigh muscles was associated with the presence of symptomatic spinal stenosis, reduced functional walking capacity, and reduced lower limb muscle strength. The causality between spinal stenosis, accumulation of thigh MFI, and surgical outcomes need further study. We have demonstrated that MRI might serve as an objective muscle biomarker in future achondroplasia studies, in addition to functional outcome measures. The method could potentially aid in optimizing the timing of spinal decompression surgery and in planning of post-surgery rehabilitation.

Cardiovascular risk factors and body composition in adults with achondroplasia.

PURPOSE: An increased cardiovascular mortality has been reported in achondroplasia. This population-based, case-control study investigated cardiovascular risk factors and body composition in Norwegian adults with achondroplasia. METHODS: We conducted anthropometric, clinical, and laboratory assessments in 49 participants with achondroplasia, of whom 40 completed magnetic resonance imaging (MRI) for body composition analysis. Controls consisted of 98 UK Biobank participants, matched for body mass index (BMI), sex, and age. RESULTS: Participants were well matched for BMI (33.3 versus 32.5 kg/m2) and sex, but achondroplasia participants were younger than controls (mean age 41.1 versus 54.3 years). Individuals with achondroplasia had lower age-adjusted mean blood pressure, total and low-density lipoprotein (LDL) cholesterol, and triglycerides compared with controls, but similar fasting glucose and HbA1c values. Age-adjusted mean visceral fat store was 1.9 versus 5.3 L (difference -2.7, 95% confidence interval [CI] -3.6 to -1.9; P < 0.001), abdominal subcutaneous fat was 6.0 versus 11.2 L (-4.7, 95% CI -5.9 to -3.4; P < 0.001), and liver fat was 2.2 versus 6.9% (-2.8, 95% CI -5.2 to -0.4; P = 0.02). CONCLUSION: Despite a high BMI, the cardiovascular risks appeared similar or lower in achondroplasia compared with controls, indicating that other factors might contribute to the increased mortality observed in this condition.

Correction to: High prevalence of symptomatic spinal stenosis in Norwegian adults with achondroplasia: a population-based study.

An amendment to this paper has been published and can be accessed via the original article.

High prevalence of symptomatic spinal stenosis in Norwegian adults with achondroplasia: a population-based study.

BACKGROUND: Symptomatic spinal stenosis (SSS) is a well-known medical complication in achondroplasia. The reported prevalence of SSS is 10 to 30%, an estimate based on small studies or selected populations. No population-based studies exist currently. Furthermore, the relationship between SSS and physical functioning has not been investigated in detail. The aims of this study were to describe the prevalence of SSS in Norwegian adults with achondroplasia, and to explore the impact of SSS on physical functioning. METHODS: This was a population-based study on Norwegian community-dwelling adults with genetically confirmed achondroplasia. Prevalence of SSS was defined by clinical symptoms, and confirmed by imaging or surgical reports. Physical functioning was assessed by walking capacity (6-min walk test), hand strength (Grippit), and activities of daily living (the Health Assessment Questionnaire, HAQ). Pain was assessed by pain site locations and intensity (Numeric Rating Scale, NRS). RESULTS: In total, 50 participants were included (27 males, 23 females). Median age was 41 years (range 16 to 87 years), 34 (68%) had SSS. The estimated median age at first symptom onset was 33 years (95% confidence interval (CI) 29 to 43 years), range 10 to 67 years. The majority had multiple spinal levels affected. The walking distance was 110 m shorter in the SSS group (95% CI - 172 to - 40 m) as compared with the non-SSS group (p < 0.01). There was no considerable difference in hand strength between the two groups. Mean HAQ scores (0-3) for walking and hygiene were significantly higher in the SSS group, reflecting more activity limitations. Mean differences were 0.9 (95% CI 0.3 to 1.4, p < 0.01) and 0.6 (95% CI 0.2 to 1.0, p < 0.01). Pain intensity (NRS 0-10) was also significantly higher in the SSS group with a mean difference of 3.2 (95% CI 0.6 to 5.6, p = 0.02). CONCLUSIONS: SSS was highly prevalent in Norwegian adults with achondroplasia, with symptom onset at young age, and multiple spinal levels affected. The presence of SSS was associated with reduced walking distance, activity limitations, and more pain. The findings underline the importance of thorough assessment and monitoring of SSS in achondroplasia, including a formal assessment of physical functioning.

Should calculation of chemotherapy dosage for bowel cancer be based on body composition? / Bør beregning av cellegiftdose ved tarmkreft baseres på kroppssammensetning?

BACKGROUND: Dosage of chemotherapy for colon cancer is currently based on the patient's body surface area. Several studies have identified an association between low fat-free mass and chemotherapy toxicity among patients with metastatic colorectal cancer. This has been less widely studied for localised disease. This review aims to summarise studies that have investigated the association between clinical signs of disease-related malnutrition (low body mass index, weight loss and low muscle mass) and tolerance of chemotherapy in patients with localised colon cancer. MATERIAL AND METHOD: We conducted a systematic search in PubMed with various synonyms of the terms 'colorectal cancer', 'adjuvant chemotherapy', 'nutritional status' and 'toxicity'. The search was concluded in May 2019. Of 553 articles, 39 were considered relevant and read in full text. Ten of these fulfilled the inclusion criteria for this review. RESULTS: Nine of the ten studies indicate an association between clinical signs of disease-related malnutrition and dose-limiting toxicity. The association appears to be especially pronounced in patients with low fat-free mass. INTERPRETATION: The results support the hypothesis that there is an association between disease-related malnutrition and the prevalence of toxicity and modification of the course of adjuvant chemotherapy in patients with localised colon cancer. The potential benefits of basing chemotherapy dosage on body composition in addition to body surface area should be investigated in clinical trials.

Paranasal sinus opacification in headache sufferers: A population-based imaging study (the HUNT study-MRI).

Background The association between headache and paranasal sinus disease is still unclear. Because of symptom overlap, the two conditions are not easily studied on the basis of symptoms alone. The aim of the present study was to investigate whether paranasal sinus opacification on magnetic resonance imaging (MRI) was associated with migraine, tension-type headache (TTH) or unclassified headache. Methods This was a cross-sectional study of 844 randomly selected participants (442 women, age range 50-65 years, mean age 57.7 years). Based on 14 headache questions, participants were allocated to four mutually exclusive groups: migraine, TTH, unclassified headache or headache free. On MRI, opacifications as mucosal thickening, polyps/retention cysts and fluid in the five paired sinuses were measured and recorded if ≥1 mm. For each participant, opacification thickness was summed for each sinus and, in addition, a total sum of all sinuses was calculated. Opacification in each sinus was compared between headache-free participants and the headache groups using non-parametric tests, and the total sum was compared by logistical regression. Results No significant association was found between paranasal sinus opacification and headache in general, nor when headache was differentiated into migraine, TTH and unclassified headache. This was also true in separate analyses of mucosal thickening and fluid and of opacification from each paranasal sinus. Conclusion Migraine, TTH and unclassified headache were found not to be associated with an increased degree of paranasal sinus opacification at MRI.

Paranasal sinus opacification at MRI in lower airway disease (the HUNT study-MRI).

The study builds on the concept of united airways, which describes the link between the upper and lower airways. Explorations of this concept have mainly related to asthma and less to chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate paranasal sinus opacification at magnetic resonance imaging (MRI) in COPD, self-reported asthma and respiratory symptoms. In this cross-sectional study, 880 randomly selected participants in the Nord-Trøndelag health survey (HUNT) (mean age 57.7 years, range 50-66 years, 463 women) were investigated using MRI of the paranasal sinuses. Participants were allocated to four mutually exclusive groups: (1) COPD (n = 20), (2) asthma (n = 89), (3) respiratory symptoms (n = 199), and (4) reference group (n = 572). Paranasal sinus opacifications were categorised as mucosal thickening, polyps and retention cysts, and fluid. In each participant, measurements ≥1 mm from all sinuses were summed to give a total for each category of opacities. The sums for these three categories were further added together, and referred to as the total sum. Using the 75th percentile cut-off values, the likelihood of having paranasal sinus opacifications was more than six times higher in participants with COPD and twice as high in participants with asthma than among the reference group. Respiratory symptoms were only associated with mucosal thickening. The present study shows that paranasal sinus opacification is associated not only with asthma, but also with COPD and respiratory symptoms. This is in accordance with the united airways hypothesis, and should be kept in mind when handling patients with these conditions.

Incidental findings in MRI of the paranasal sinuses in adults: a population-based study (HUNT MRI).

BACKGROUND: Diagnostic imaging of the head is used with increasing frequency, and often includes the paranasal sinuses, where incidental opacifications are found. To determine the clinical relevance of such findings can be challenging, and for the patient such incidental findings can give rise to concern if they are over-reported. Studies of incidental findings in the paranasal sinuses have been conducted mostly in patients referred for diagnostic imaging, hence the prevalence in the general population is not known. The purpose of this study was to determine the prevalence and size of incidental opacification in the paranasal sinuses in a non-selected adult population using magnetic resonance imaging (MRI) without medical indication, and to relate the results to sex and season. METHODS: Randomly and independent of medical history, 982 participants (518 women) with a mean age of 58.5 years (range, 50-66) underwent MRI of the head as part of a large public health survey in Norway. The MRIs included 3D T1 weighted volume data and 2D axial T2 weighted image (WI). Opacifications, indicating mucosal thickenings, polyps, retention cysts, or fluid, were recorded if measuring more than 1 mm. RESULTS: Opacifications were found in 66% of the participants. Mucosal thickenings were found in 49%, commonly in the maxillary sinuses (29%) where 25% had opacifications that were less than 4 mm in size. Other opacifications occurred in the anterior ethmoid (23%), posterior ethmoid (21%), frontal sinus (9%), and sphenoid (8%). Polyps and retention cysts were also found mainly in the maxillary sinuses in 32%. Fluid was observed in 6% of the MRIs. Mucosal thickening was observed more frequently in men than in women (P <0.05). No seasonal variation was found. CONCLUSIONS: In this large non-selected sample, incidental opacification in the paranasal sinuses was seen in two out of three participants, and mucosal thickening was seen in one out of two. Fluid was rare. Knowledge of incidental opacification is important because it can affect clinical practice.

Metformin in patients with non-alcoholic fatty liver disease: a randomized, controlled trial.

OBJECTIVE: The antidiabetic agent metformin is regularly discussed as a promising treatment for non-alcoholic fatty liver disease (NAFLD), which is characterized by insulin resistance. However, the evidence for its beneficial effects is limited, and conflicting reports have been published. The purpose of this study was to conduct a randomized, double-blind, placebo-controlled trial to test whether metformin improves liver histology in patients with non-alcoholic fatty liver disease. MATERIAL AND METHODS: Forty-eight patients with biopsy-proven NAFLD were randomized to treatment with metformin (n=24) or placebo (n=24) for 6 months. A second liver biopsy was obtained in all subjects who completed the trial (n=44). Data analyses are restricted to this group (per-protocol analyses). The primary outcome was changes in histologically assessed liver steatosis. Secondary outcomes were changes in NAFLD activity (NAS)-score, liver steatosis assessed by computed tomography (CT), liver transaminases, body-weight, metabolic variables and inflammatory markers. RESULTS: No significant differences between treatment with metformin or placebo were observed for changes in liver steatosis, assessed either histologically or by CT, NAS-score, liver transaminases or on markers of insulin resistance or inflammation. In contrast, beneficial effects of metformin were observed on changes in body-weight (p<0.001), serum levels of cholesterol (p=0.004), LDL-cholesterol (p<0.001), glucose (p=0.032) and on HbA1c (p=0.020). CONCLUSIONS: Treatment with metformin for 6 months was no better than placebo in terms of improvement in liver histology in patients with NAFLD. Nevertheless, the use of metformin could still be beneficial in this group as it is associated with a reduction in serum levels of lipids and glucose. (ClinicalTrials.gov number, NCT00303537).