Assessing Cut-off Points of Eosinophils, Nasal Polyp, and Lund-Mackay Scores to Predict Surgery in Nasal Polyposis: A Real-World Study.

BACKGROUND: Developing tools to identify chronic rhinosinusitis with nasal polyps (CRSwNP) patients requiring surgical treatment would help clinicians treat patients more effectively. The aim of this retrospective cross-sectional study was to identify cut-off values ​​for eosinophil percentage, nasal polyps (NP), and Lund-Mackay (LM) scores that may predict the need for surgical treatment in Finnish CRSwNP patients. METHODS: Data of CRSwNP patients (N = 378) undergoing consultation for ESS in 2001-19 were used. Data was collected from patient records and Lund-Mackay scores were determined from sinus computed tomography scans. The percentage of eosinophils was microscopically evaluated from the polyp samples available (n = 81). Associations were analyzed by Mann Whitney U test, and cut-off values by the area under the receiver operating characteristic curve (AUROC). RESULTS: ESS was performed to 293 (77.5%) of patients. Polyp eosinophilia was associated significantly with ESS (p = 0.001), whereas peripheral blood eosinophil count, LM- score and endoscopic NP- score were not (p > 0.05). AUROC values (95% CI) for detecting those needing ESS were for polyp eosinophilia 0.71 (0.60-0.83), p = 0.001, for LM score 0.59 (0.50-0.67), p = 0.054; for NP score 0.56 (0.48-0.64), p = 0.17, and for blood eosinophil count 0.68 (0.46-0.90), p = 0.08. With the threshold value of polyp eosinophilia (>25%), the sensitivity and specificity were optimal for detecting the group needing ESS from the group not undergoing ESS. The cut-off value of blood eosinophil count (>0.26 × 109/L) had relatively good, yet statistically insignificant (underpowered), predictive potential. Moderate cut-off values were found for endoscopic LM score (≥14/24) and NP score (≥4/8). CONCLUSIONS: Polyp eosinophilia (>25%) predicted ESS among Finnish hospital-level CRSwNP patients. A future challenge would be to find less invasive and cost-effective clinical factors predicting uncontrolled CRSwNP.

The Effect of Metatarsal Padding on Pain and Functional Ability in Metatarsalgia.

BACKGROUND AND AIMS: Many kinds of insoles and pads are commonly used as a conservative treatment of metatarsalgia. However, earlier studies of insole treatment provide contradictory results, and the natural progression of metatarsalgia is still unknown. The aims of this study were to (1) determine whether simple custom-made metatarsal pad insoles reduce pain and improve functional ability, (2) find out patients' satisfaction with padding treatment, and (3) investigate predisposing factors for metatarsalgia. MATERIAL AND METHODS: All metatarsalgia patients provided with metatarsal pad insoles during a 2-year period at Kuopio University Hospital (n = 45) were included in the study and observed at least a year. In all, 25 patients were interviewed about their situation before and after treatment. The Numeric Rating Scale for pain and American Orthopaedic Foot & Ankle Society forefoot questionnaire included questions about predisposing factors, other diseases, exercise, work, shoes, and satisfaction with insoles. Foot X-rays taken from 45 patients during treatment were analyzed. RESULTS: The mean age of the patients was 56 years (range 34-84 years); 87% of them were women. In all, 47% of patients had osteoarthritic changes in the first metatarsophalangeal joint, and 42% had hallux valgus. In the interviewed subgroup (n = 25) body mass index was normal in 44%, and 36% were mildly overweight. High-heeled shoes were used by 40% daily, and 68% had done standing work for several years. Pain decreased significantly on the Numeric Rating Scale: 3.2 points in all patients ( p < 0.001), 3.1 points among women, and 4.25 points among men. The American Orthopaedic Foot & Ankle Society score improved 24.2 points in all patients ( p < 0.001, range 0-100), among women 19 points, and among men 29 points. CONCLUSION: Metatarsalgia affects mostly women and is often preceded by extensive use of high heels and standing work. Also, a high association of first metatarsophalangeal arthrosis and hallux valgus was found. Metatarsal pads reduce pain and improve the American Orthopaedic Foot & Ankle Society score. We recommend metatarsal padding as a safe and inexpensive alternative in treating metatarsalgia patients.

Amount of weight loss or gain influences the severity of respiratory events in sleep apnea.

Severity of obstructive sleep apnea (OSA) is estimated based on respiratory events per hour [i.e., apnea-hypopnea index (AHI)]. The aim of this study was to investigate effects of weight change on the severity of respiratory events. Respiratory event severity, including duration and morphology, was estimated by determining parameters quantifying obstruction and desaturation event lengths and areas, respectively. Respiratory events of 54 OSA patients treated with dietary intervention were evaluated at baseline and after 5-year follow-up in subgroups with different levels of weight change. AHI, oxygen desaturation index (ODI) and obstruction event severities decreased during weight loss. In lower level weight loss, the decrease was milder in obstruction severity than in AHI and ODI, indicating that the decrease in the number of events is more focused on less severe events. In weight gain groups, parameters incorporating obstruction event severity, AHI and ODI increased, although increase was greater in parameters incorporating obstruction event severity. The number and severity of respiratory events were modulated differently by the level of weight change. AHI misses this change in the severity of respiratory events. Therefore, parameters incorporating information on the respiratory event severities may bring additional information on the health effects obtained with dietary treatment of OSA.

Weight loss alters severity of individual nocturnal respiratory events depending on sleeping position.

Weight loss is an effective treatment for obstructive sleep apnea (OSA). The mechanisms of how weight loss affects nocturnal breathing are not fully understood. The severity of OSA is currently estimated by the number of respiratory events per hour of sleep (i.e. apnea-hypopnea-index, AHI). AHI neglects duration and morphology of individual respiratory events, which describe the severity of individual events. In the current paper, we investigate the novel Adjusted-AHI parameter (incorporating individual event severity) and AHI after weight loss in relation to sleeping position. It was hypothesised that there are positional differences in individual event severity changes during weight loss. Altogether, 32 successful (> 5% of weight) and 34 unsuccessful weight loss patients at baseline and after 1 year follow-up were analysed. The results revealed that individual respiratory event severity was reduced differently in supine and non-supine positions during weight loss. During weight loss, AHI was reduced by 54% (p = 0.004) and 74% (p < 0.001), while Adjusted-AHI was reduced by 14% (p = 0.454) and 48% (p = 0.003) in supine and non-supine positions, respectively. In conclusion, the severity of individual respiratory events decreased more in the non-supine position. The novel Adjusted-AHI parameter takes these changes into account and might therefore contribute additional information to the planning of treatment of OSA patients.

Novel parameters reflect changes in morphology of respiratory events during weight loss.

Apnea-hypopnea-index (AHI), disregarding the respiratory event morphology, is currently used in estimation of severity of obstructive sleep apnea (OSA). The purpose of the current study was to evaluate the potential of novel parameters in estimation of changes in severity of OSA during weight loss. Polygraphic data of 67 patients, 37 in the control (no weight loss) and 30 in the weight loss (>5%) groups was evaluated at baseline and after two year follow-up. Changes in the values of novel parameters, incorporating detailed information of respiratory event characteristics, were evaluated and compared with changes in AHI. The median AHI in the weight loss group decreased significantly during the follow-up. The number of shorter respiratory events decreased in the weight loss group, while the longer ones remained, increasing the median durations of the respiratory events by 20-62%. For this reason the decrease of the values of the novel parameters were smaller compared to AHI in the weight loss group. This suggests that the severity of OSA might not fall as linearly during weight loss as AHI suggests. Moreover, the novel parameters containing more detailed information on the morphology characteristics may provide valuable supplementary information for the assessment of the severity of OSA.

Effect of weight loss on inflammation in patients with mild obstructive sleep apnea.

BACKGROUND AND AIMS: Inflammation may be one mediating mechanism for cardiovascular diseases in obstructive sleep apnea (OSA). However, little is known about subclinical inflammation or the effect of lifestyle intervention on inflammation in early stages of OSA. The aim of this substudy of an existing randomized controlled trial, with post hoc analyses, was to determine the impact of lifestyle changes aimed at weight reduction on inflammatory biomarkers in overweight patients with mild OSA. METHODS AND RESULTS: Patients were randomized to supervised intensive lifestyle intervention group (N=28) or to control group (N=31), which received routine lifestyle advices. Circulating concentrations of pro- and anti-inflammatory mediators were measured before and after the 1-year intervention. The concentrations of two pro-inflammatory mediators, high-sensitivity C-reactive protein (hsCRP) and interleukin (IL)-6, decreased significantly in both groups. Although the changes in inflammatory biomarkers favored the supervised lifestyle intervention, the only significant reduction observed between the groups was for the anti-inflammatory IL-1 receptor antagonist (IL-1RA). The change in hsCRP was associated with apnea-hypopnea index, and improving night-time oxygen saturation was related to tumor necrosis factor alpha. IL-1RA and IL-6 were associated with insulin metabolism. CONCLUSION: Weight loss resulted in reductions in concentrations of some pro- and anti-inflammatory mediators in overweight patients with mild OSA, overall favoring the supervised lifestyle intervention. These findings suggest that more intensive treatment of obesity in OSA patients might be well-justified.

Abnormal response to physical activity in femurs after heterozygous inactivation of one allele of the Col2a1 gene for type II collagen in mice.

The objective of this study was to evaluate the influence of heterozygous inactivation of one allele of the type II collagen gene (Col2a1) on biomechanical properties and mineral density of bone under physical loading conditions. C57BL/6-TGN mice with heterozygous knockout (HZK) inactivation of Col2a1 gene and their nontransgenic littermate controls were housed in individual cages with running wheels for 9 and 15 months. The running activity of each mouse was monitored continuously throughout the experiment. Bone mineral density (BMD) of mice femora was measured using dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computerized tomography (pQCT). Biomechanical properties were determined using three-point bending tests. Vertebral bone samples were prepared for quantitative polarized light microscopy and digital densitometry of proteoglycans. The concentration of total collagen and collagen cross-links were analyzed using high-performance liquid chromatograpy (HPLC). The average daily running distance was shorter for the HZK mice between the age of 4 and 15 months as compared with normal runners (P < 0.05). The ultimate breaking force was 14.8% and 23.6% (9 vs. 15 months) lower in HZK-runners than in wild-type runners. BMD of the femur was 6.1% lower in HZK-runners at the age of 9 months (P < 0.05). Physical activity increased cortical BMD in wild-type runners but not in the HZK runners at the age of 9 months. The collagen network of the HZK mice was less organized. There were only minor changes in BMD and mechanical and structural properties between sedentary HZK mice and their wild-type controls. Increased physical activity induced significantly lower bone density, mechanical properties, and organization of collagen fibers in male HZK mice. However, there were no major differences in biomechanical parameters between sedentary HZK and wild-type male mice. This suggests an important guiding role of collagen type II in bone remodelling and maturation.

Lifelong voluntary joint loading increases osteoarthritis in mice housing a deletion mutation in type II procollagen gene, and slightly also in non-transgenic mice.

OBJECTIVES: To investigate the effects of voluntary running on the incidence and severity of osteoarthritis (OA) and associated changes in cartilage matrix and subchondral bone in a transgenic Del1 mouse model for OA. METHODS: Del1 mice and their non-transgenic littermate controls were housed from the age of 5-6 weeks to 15 months in individual cages with running wheels. The running activity of each mouse was monitored for the entire 12 month period. Additional Del1 and control mice were housed in individual cages without running wheels. At the end of the experiment the severity of OA was evaluated by light microscopy, and the articular cartilage matrix changes by digital densitometry and quantitative polarised light microscopy. RESULTS: Lifelong voluntary running increased the incidence and severity of OA significantly in Del1 mice (transgenic runners), and slightly also in non-transgenic runners. Severe OA changes increased from 39% in transgenic non-runners to 90% in transgenic runners (p=0.006) in lateral tibial condyles, and from 24% to 80% (p=0.013) in lateral femoral condyles, respectively. The proteoglycan content of articular cartilage was reduced in transgenic runners in comparison with transgenic non-runners (p=0.0167), but a similar effect was not seen in non-transgenic runners compared with non-transgenic non-runners. No attributable differences were seen in the collagen network of articular cartilage or in the subchondral bone between any of the groups. CONCLUSION: The Del1 mutation has earlier been shown to disturb the assembly of the cartilage collagen network and thereby increase the incidence and severity of OA with age. In this study, voluntary running was shown to increase further cartilage damage in the lateral compartments of the knee. This suggests that articular cartilage in Del1 mice is less resistant to physical loading than in control mice. Despite severe OA lesions in the knee joint at the age of 15 months, Del1 mice continued to run voluntarily 2-3 km every night.

Premature vertebral endplate ossification and mild disc degeneration in mice after inactivation of one allele belonging to the Col2a1 gene for Type II collagen.

STUDY DESIGN: Skeletal tissues of mice with an inactivated allele of the Col2a1 gene for Type II collagen ("heterozygous knockout") were studied. OBJECTIVE: To determine whether a heterozygous inactivation of the Col2a1 gene has a role in the etiology of spine disorders such as disc degeneration. SUMMARY OF BACKGROUND DATA: Mutations in the COL2A1, COL11A1, COL11A2, and COL9A2 genes have been linked to spine disorders. However, the mechanism by which genetic factors lead to disc degeneration still are largely unknown. METHODS: Spine tissues were studied using radiograph analyses; conventional, quantitative, and polarized light microscopy; immunohistochemistry for the major extracellular components, and in situ hybridization for procollagens alpha1(I) and alpha1(II). Voluntary running activity also was monitored in half of the mice. RESULTS: As the findings showed, 1-month-old heterozygous knockout mice had shorter limb bones, skulls, and spines, as well as thicker and more irregular vertebral endplates, which calcified earlier than in the control mice. They also had a lower concentration of glycosaminoglycans in the anulus fibrosus, in the endplates, and in the vertebral bone than the controls. These features in the heterozygous knockout mice were compensated by the age of 15 months. However, the long bones and skulls of the mature heterozygous mice remained shorter than those of the controls. Gene-deficient mice used the running wheel less. However, physical exercise did not induce any marked structural changes in the skeleton. CONCLUSION: Mice with heterozygous knockout of Col2a1 show subtle early skeletal manifestations that bear some resemblance to those of human spine disorders.