Structural and Functional Changes of Hands and Legs in Early Rheumatoid Arthritis.

Background and Objectives: The aim of this study was to assess if there are structural and functional changes of hands and legs already in early rheumatoid arthritis (ERA), compared with the population-based control group. Additionally, we aimed to identify if the changes are symmetrical in hands and legs and if there are factors that are associated with these changes. The study was conducted, and, thus far, the results have been controversial. Materials and Methods: The study group consisted of 83 consecutive patients with ERA and 321 control subjects. Dual-Energy X-Ray Absorptiometry (DXA) machine was used to measure bone, lean and fat mass. Inflammation and bone markers, smoking and nutritional habits were assessed, to evaluate the effects of different factors. The 30-Second Chair Stand Test (30-CST) and the Handgrip Strength Test (HST) were used to estimate muscle strength. Results: The presence of ERA was associated with lower arm, leg lean mass and higher fat mass of arm, compared with control subjects. ERA was also associated with lower mean handgrip in HST and worse muscle strength of legs in the 30-CST. Bone mass changes were not so evident both in arms and legs. Smoking habits did not seem to have relevant effect on bone mass, muscle structural and functional changes, both on hands and legs. In ERA, lean mass of arm and leg was negatively associated with C-reactive protein (CRP). The intake of proteins in ERA was not associated with lean mass changes both in hands and legs. Conclusions: Structural and functional changes of hands and legs are different in ERA. ERA patients had higher fat mass of arm, lower lean mass of arm and leg and, accordingly, decreased muscle function. The lowering of lean mass of arm and leg in ERA was associated with the elevation of CRP.

EULAR/eumusc.net standards of care for rheumatoid arthritis: cross-sectional analyses of importance, level of implementation and care gaps experienced by patients and rheumatologists across 35 European countries.

OBJECTIVE: As part of European League against Rheumatism (EULAR)/European Musculoskeletal Conditions Surveillance and Information Network, 20 user-focused standards of care (SoCs) for rheumatoid arthritis (RA) addressing 16 domains of care were developed. This study aimed to explore gaps in implementation of these SoCs across Europe. METHODS: Two cross-sectional surveys on the importance, level of and barriers (patients only) to implementation of each SoC (0-10, 10 highest) were designed to be conducted among patients and rheumatologists in 50 European countries. Care gaps were calculated as the difference between the actual and maximum possible score for implementation (ie, 10) multiplied by the care importance score, resulting in care gaps (0-100, maximal gap). Factors associated with the problematic care gaps (ie, gap≥30 and importance≥6 and implementation<6) and strong barriers (≥6) were further analysed in multilevel logistic regression models. RESULTS: Overall, 26 and 31 countries provided data from 1873 patients and 1131 rheumatologists, respectively. 19 out of 20 SoCs were problematic from the perspectives of more than 20% of patients, while this was true for only 10 SoCs for rheumatologists. Rheumatologists in countries with lower gross domestic product and non-European Union countries were more likely to report problematic gaps in 15 of 20 SoCs, while virtually no differences were observed among patients. Lack of relevance of some SoCs (71%) and limited time of professionals (66%) were the most frequent implementation barriers identified by patients. CONCLUSIONS: Many problematic gaps were reported across several essential aspects of RA care. More efforts need to be devoted to implementation of EULAR SoCs.

Patients with rheumatoid arthritis facing sick leave or work disability meet varying regulations: a study among rheumatologists and patients from 44 European countries.

OBJECTIVES: To describe and explore differences in formal regulations around sick leave and work disability (WD) for patients with rheumatoid arthritis (RA), as well as perceptions by rheumatologists and patients on the system's performance, across European countries. METHODS: We conducted three cross-sectional surveys in 50 European countries: one on work (re-)integration and social security (SS) system arrangements in case of sick leave and long-term WD due to RA (one rheumatologist per country), and two among approximately 15 rheumatologists and 15 patients per country on perceptions regarding SS arrangements on work participation. Differences in regulations and perceptions were compared across categories defined by gross domestic product (GDP), type of social welfare regime, European Union (EU) membership and country RA WD rates. RESULTS: Forty-four (88%) countries provided data on regulations, 33 (75%) on perceptions of rheumatologists (n=539) and 34 (77%) on perceptions of patients (n=719). While large variation was observed across all regulations across countries, no relationship was found between most of regulations or income compensation and GDP, type of SS system or rates of WD. Regarding perceptions, rheumatologists in high GDP and EU-member countries felt less confident in their role in the decision process towards WD (ß=-0.5 (95% CI -0.9 to -0.2) and ß=-0.5 (95% CI -1.0 to -0.1), respectively). The Scandinavian and Bismarckian system scored best on patients' and rheumatologists' perceptions of regulations and system performance. CONCLUSIONS: There is large heterogeneity in rules and regulations of SS systems across Europe in relation to WD of patients with RA, and it cannot be explained by existing welfare regimes, EU membership or country's wealth.

Factors Associated With Low Lean Mass in Early Rheumatoid Arthritis: A Cross- Sectional Study.

Background and Objectives: The aim of the study was to evaluate body composition (BC) of rheumatoid arthritis (RA) patients at disease onset compared to population controls focusing on the associations between low lean mass and disease specific parameters, nutritional factors and physical activity. Materials and Methods: 91 patients with early rheumatoid arthritis (ERA) (72% female) and 328 control subjects (54% female) were studied. BC- lean and fat mass parameters were measured with a Lunar Prodigy Dual Energy X-Ray Absorptiometry (DXA) machine. The prevalence, age and gender adjusted odds ratios of having low lean mass and overfat, associations between nutrition, physical activity, and ERA disease specific parameters and the presence of low lean mass were evaluated. Results: We found that the BC of patients with recent onset RA differs from control subjects-ERA patients had a higher mean body fat percentage (BFP) and lower appendicular lean mass (ALM). 41.8% of the ERA patients and 19.8% of the controls were classified as having low lean mass adjusted OR 3.3 (95% C.I. 1.9-5.5, p < 0.001). 68.1% of the ERA subjects and 47.3% of the controls were overfat (adjusted OR 1.9 (95% C.I. 1.1-3.3, p = 0.02)) and the adjusted odds of having both low lean mass and overfat were 4.4 times higher (26.4% vs. 7.0% 95% C.I. 2.3-8.4, p < 0.001) among the ERA group. Higher ESR (OR 1.03, C.I.1.002-1.051, p = 0.03), CRP (OR 1.03, C.I. 1.002-1.061, p = 0.04), lower protein intake (OR 0.98 C.I. 0.96-0.99, p = 0.04), corticosteroid usage (OR 3.71 C.I. 1.4-9.9, p < 0.01) and lower quality of life (higher HAQ score OR 2.41 C.I. 1.24-4.65, p < 0.01) were associated with having low lean mass in the ERA group (adjusted to age and gender). Conclusions: Patients with early RA have lower appendicular lean mass and higher body fat percentage compared to healthy controls. Loss of lean mass in early RA is associated with elevated inflammatory markers inducing catabolism, lower protein intake and also with GCS treatment.

The metabolic profile in early rheumatoid arthritis: a high prevalence of metabolic obesity.

The aim of the study was to compare the prevalence of metabolic syndrome (MetS) in early RA patients with age-gender-matched population controls focusing on the presence of MetS in different weight categories. The study group consisted of 91 consecutive patients with early RA and 273 age- and gender-matched controls subjects. MetS was diagnosed according to the National Cholesterol Education Program (NCEP-ATP III) criteria. Mean age in both groups was 52 years, and 72.5 % were female. The prevalence of MetS did not differ between the two groups (35.2 % in RA, 34.1 % in control group). Mean systolic blood pressure in the RA group was 137 mmHg, in control group 131 mmHg, P = 0.01, and diastolic blood pressure 85 versus 81 mmHg, respectively (P < 0.01). We found that 20 of 65 (30.8 %) of RA patients compared to 80 of 152 (52.6 %) of the control subjects with elevated blood pressure received antihypertensive treatment (P < 0.01). When comparing subgroups with normal BMI, the odds of having MetS (being metabolically obese) were higher among early RA subjects (OR 5.6, CI 1.3-23.8). Of the individual components of metabolic syndrome, we found increased prevalence of hypertension (OR 2.8, CI 1.3-6.0) and hyperglycemia (OR 2.9, CI 1.0-8.0) in the RA group. Recognition of abnormal metabolic status among normal-weight RA patients who have not yet developed CVD could provide a valuable opportunity for preventative intervention.

Adverse lifestyle and health-related quality of life: gender differences in patients with and without chronic conditions.

OBJECTIVES: The aim was to investigate the relationship between the main lifestyle-related factors and health-related quality of life (HRQoL) in a sample of patients with and without chronic conditions (CCs) with respect to the gender differences in both groups. METHODS: A cross-sectional study was conducted on 1061 patients (of which 308 had no CCs and 753 of those had one or more CCs) recruited at primary health care centres and the Internal Medicine Clinic at Tartu University Hospital in Estonia. Data were collected during 2012-2014. The patient's age, self-reported smoking status, alcohol consumption (assessed by Alcohol Use Disorders Identification Test) and body mass index were used as independent variables to predict the physical component scores (PCS) and mental component scores (MCS) of HRQoL (assessed by SF-36). RESULTS: Smoking had a negative association with both physical and mental components of HRQoL only in women with CCs. Further, the PCS of chronically ill women was negatively associated with the higher body mass index. Harmful drinking had a negative association with the HRQoL in all patient groups, except with the PCS in women with CC. Light alcohol consumption without symptoms of harmful use or dependency had a positive association with the physical and mental HRQoL in all patient groups, except with the MCS in women without CCs. CONCLUSION: Adverse lifestyle had the most expressed association with HRQoL in women with CCs. Light alcohol consumption had a positive association, but harmful use of alcohol had an inverse association with HRQoL irrespective of patients' gender or health status.

High dose vitamin D supplementation decreases the risk of deficiency in male conscripts, but has no effect on physical performance-A randomized study.

Purpose: Physical load during military training might increase the need for vitamin D; therefore, supplementation could be beneficial for 25(OH)D serum levels and physical performance. Methods: One hundred and twelve male conscripts were randomized into two vitamin D oil capsule supplementation groups: 55 participants in the 600 IU group and 57 in the 4000 IU group with a follow-up period from July 2021 to May 2022. Physical fitness tests were performed in July, October and May. Hand grip strength tests were performed in July, October and January. Blood serum (25(OH)D), parathyroid hormone PTH), calcium and ionized calcium (i-Ca) values were measured in July, October, January and May. Results: The 600 IU group had a lower (p < 0.001) value of 25(OH)D at all time points compared to the 4000 IU group, except at baseline. None of the subjects in the 600 IU group reached sufficient levels of 75 nmol/L of 25(OH)D in January and May. In May, 60% of participants in the 600 IU group and 30% in the 4000 IU group had 25(OH)D levels under 50 nmol/L. No significant differences in PTH or i-Ca values were found between the study groups at any time point. No significant differences at any time point were found in the physical fitness test or hand grip strength test between the groups. Conclusion: A 10-month vitamin D supplementation with 4000 IU decreased the incidence of vitamin D deficiency (<75 nmol/L) in young, male army conscripts during wintertime, but no differences in physical performance were found compared to 600 IU supplementation. Level of Evidence: Level I, Prospective randomized study.

Toward Adoption of Health Risk Assessment in Population-Based and Clinical Scenarios: Lessons From JADECARE.

Introduction: Health risk assessment (HRA) strategies are cornerstone for health systems transformation toward value-based patient-centred care. However, steps for HRA adoption are undefined. This article analyses the process of transference of the Adjusted Morbidity Groups (AMG) algorithm from the Catalan Good Practice to the Marche region (IT) and to Viljandi Hospital (EE), within the JADECARE initiative (2020-2023). Description: The implementation research approach involved a twelve-month pre-implementation period to assess feasibility and define the local action plans, followed by a sixteen-month implementation phase. During the two periods, a well-defined combination of experience-based co-design and quality improvement methodologies were applied. Discussion: The evolution of the Catalan HRA strategy (2010-2023) illustrates its potential for health systems transformation, as well as its transferability. The main barriers and facilitators for HRA adoption were identified. The report proposes a set of key steps to facilitate site customized deployment of HRA contributing to define a roadmap to foster large-scale adoption across Europe. Conclusions: Successful adoption of the AMG algorithm was achieved in the two sites confirming transferability. Marche identified the key requirements for a population-based HRA strategy, whereas Viljandi Hospital proved its potential for clinical use paving the way toward value-based healthcare strategies.

Does Dietary Polyunsaturated Fatty Acid Intake Associate With Bone Mineral Density and Limb Structural Changes in Early Rheumatoid Arthritis?

Background: Rheumatoid arthritis (RA) is an inflammatory disease that can result in bone erosion, lean mass lowering, and increase of fat mass without changes in body weight. The dietary consumption of polyunsaturated fatty acids (PUFAs) has been assessed in many studies due to their potential anti-inflammatory effect. Aim: The aim of this research was to identify if dietary intake of PUFAs associates with bone mineral density (BMD) and limb structural changes in early rheumatoid arthritis (ERA) compared to a population-based control group. The study was conducted because previous results have been insufficient. Methods: The study group consisted of 83 ERA patients and 321 control subjects. A dual-energy X-Ray absorptiometry (DXA) machine was used to measure hip, lumbar spine, and radius BMD, as well as arm and leg fat, lean, and bone mass. Dietary habits and inflammatory markers were assessed to evaluate the effects to BMD and limb structural changes. Results: In ERA subjects, higher dietary consumption of PUFAs was associated with a decrease in arm fat mass (b -28.17, P = .02) and possibly with higher lumbar BMD (b 0.008, P = .058). Limb bone and lean mass changes were not associated with dietary intake of PUFAs. Conclusion: Balanced nutrition is essential. Consuming PUFAs could be beneficial in ERA preventing structural changes to hands, but additional research is needed.

Factors associated with hand bone changes in early rheumatoid arthritis.

BACKGROUND: The aim of this research was to assess if hand bone mineral density (HBMD) changes associated with the appearance of erosions in early rheumatoid arthritis (ERA), compared with the population-based control group. Additionally, we tried to identify if there are novel factors that associate with HBMD and erosive changes (EC), and if they are dissimilar. The study was conducted as the data are limited. METHODS: The study group consisted of 83 ERA patients and 321 controls. Dual-Energy X-Ray Absorptiometry (DXA) machine was used to measure HBMD. EC of RA (rheumatoid arthritis) were assessed in X-rays of hands using Sharp scores. Life-style habits, inflammation markers were assessed to evaluate the effects of different factors. RESULTS: The presence of ERA was associated with lower HBMD compared with controls (adjusted for age, gender, height and weight; b -0.01, p = 0.045). 76% (95% CI 65.3-84.6) of ERA patients had EC in hand X-ray. Smoking habits and higher BMI (body mass index) were associated with an increased likelihood of having RA specific EC. In ERA, decreasing of HBMD was associated with the elevation of interleukin-6 (IL-6) and rheumatoid factor (RF) positivity. CONCLUSIONS: In ERA, HBMD changes were not associated with the appearance of erosions. Factors that associate in ERA with HBMD changes and appearance of erosions differ. HBMD assessment together with serum IL-6 level could be useful in everyday clinical practice for better surveillance of ERA patients who do not have EC in hand X-rays.

Severe deficiency of vitamin D has no negative effect on physical performance during military training.

BACKGROUND: Decreased physical fitness and inferior physical performance are potentially life-threatening risk factors in a combat situation. To examine the effect of vitamin D on physical performance, a prospective study of young men conscripts in the Estonian Army was designed. The hypothesis of the study was that severe deficiency of vitamin D has a negative effect on physical performance. METHODS: All conscripts (N.=410) entering 10-month military service in July 2015 at the Kuperjanov Battalion were asked to participate. Initially, a total of 98 conscripts volunteered to participate. A prospective longitudinal study with a 10-month follow-up period was performed. The Army Physical Fitness Test (APFT) was performed three times, and hand grip strength, and blood serum values of 25(OH)D, parathyroid hormone (PTH) and calcium (Ca) were measured four times. RESULTS: A significant decrease in the levels of 25(OH)D compared with baseline values were found, with a lowest mean value of 31.9 nmol/L in March 2016 (P<0.001). No significant differences were found in serum Ca levels. In March 2016, PTH was significantly higher in the severe deficiency group (<25 nmol/L of 25(OH)D) (P=0.02). No significant differences were found in terms of the APFT or hand grip strength between conscripts with severe deficiency of 25(OH)D or values >25 nmol/L. The main finding of the present study was that severe 25(OH)D deficiency was common among male conscripts during the winter season but had no negative effect on physical performance in terms of the APFT test and hand grip strength test. CONCLUSIONS: Severe vitamin D deficiency during the winter season is common but has no negative effect on physical performance in young, physically active men in military service.

Impact of a new sarco-osteopenia definition on health-related quality of life in a population-based cohort in Northern Europe.

Sarcopenia has been shown to be a marker of falling; therefore, combining osteopenia and sarcopenia could identify a frailer, higher-fracture-risk population. We aimed to define sarco-osteopenia (SOP) in a population-based healthy young sample using both muscle functional and quantitative parameters and assessing the impact of this definition on health-related quality of life. A population sample of 304 patients aged 25-70 yr was analyzed with a Lunar DPX-IQ dual-energy X-ray absorptiometry machine (GE Healthcare, Pollards Wood, UK), and their health-related quality of life was assessed with the Short-Form-36 (SF-36) questionnaire. SOP was defined as bone mineral density (BMD) -1 standard deviation (SD) and height-adjusted appendicular muscle mass -2 SD and/or grip strength -2 SD less than the mean values of 77 young individuals in the population sample (age: 25-39 yr). Our proposed SOP definition identifies 3-9% of the population older than 40 yr as sarco-osteopenic. These individuals also show markedly lower scores in the role-physical (p=0.01), vitality (p=0.03), and role-emotional (p=0.02) subscales of the SF-36 questionnaire. No difference in the quality of life was observed between osteopenic individuals and those with normal BMD. The new definition identifies a population with significant decrements in health-related quality of life.

Seven-month wintertime supplementation of 1200 IU vitamin D has no effect on hand grip strength in young, physically active males: A randomized, controlled study.

Background: There has been a growing interest in the role of vitamin D for the well-being and physical performance of humans under heavy training such as conscripts in military service; however, there is a lack of long-term supplementation studies performed on members of this type of young, physically active, male population. The hypothesis of the study was that vitamin D supplementation during wintertime will decrease the prevalence of critically low vitamin D blood serum levels and increase hand grip strength during the winter season among young male conscripts. Study Design: Longitudinal, triple-blinded, randomized, placebo-controlled trial. Methods: Fifty-three male conscripts from the Estonian Army were randomized into two groups: 27 to an intervention group and 26 to a placebo group. The groups were comparable in terms of their demographics. The intervention group received 1200 IU (30 µg) capsules of vitamin D3, and the control group received placebo oil capsules once per day. The length of the follow-up was 7 months, from October 2016 until April 2017. Blood serum vitamin D (25(OH)D), parathyroid hormone (PTH), calcium (Ca), ionized calcium (Ca-i), testosterone and cortisol values, and hand grip strength were measured four times during the study period. Results: The mean 25(OH)D level decreased significantly in the control group to a critically low level during the study, with the lowest mean value of 22 nmol/l found in March 2017. At that time point, 65% in the control group vs 15% in the intervention group had 25(OH)D values of less than 25 nmol/l (p < 0.001). In the intervention group, the levels of 25(OH)D did not change significantly during the study period. All other blood tests revealed no significant differences at any time point. The corresponding result was found for hand grip strength at all time points. Conclusion: Long-term vitamin D supplementation during wintertime results in fewer conscripts in the Estonian Army with critically low serum vitamin D (25(OH)D) levels during the winter season. However, this did not influence their physical performance in the form of the hand grip strength test.

Impact of molecularly defined hypolactasia, self-perceived milk intolerance and milk consumption on bone mineral density in a population sample in Northern Europe.

OBJECTIVE: Milk intake as a source of calcium is considered an important factor for bone mineral metabolism. Low lactase activity in adult-type hypolactasia (HL) and self-perceived lactose intolerance (LI) are the main limiting factors of milk intake. The aim of this study was to examine the relationship of HL, LI, individual milk consumption and bone mineral density in a population with high milk consumption and a prevalent vitamin D deficiency. MATERIAL AND METHODS: A population-based study of 367 men and women aged 25-70 years was conducted in Estonia. HL was diagnosed by direct sequencing of the LCT gene, bone mineral density and body composition measured by dual energy X-ray absorptiometry (DXA). An original health questionnaire was used to collect data on milk and dairy consumption, self-perceived milk intolerance, supplement usage and fracture history. RESULTS: Lactase genotype and phenotype had no effect on bone mineral density in this high milk consumption population with a prevalent vitamin D insufficiency. Milk consumption was a significant determinant of bone mineral density in Estonia. Self-perceived milk intolerance leads to self-imposed reductions in milk consumption, increases in bone turnover and an increased risk of fracture. CONCLUSIONS: Self-perceived milk-intolerance rather than HL influences milk consumption and has deleterious effects on bone metabolism.

Bone mineral density reference range in Estonia: a comparison with the standard database (NHANES III).

Dual-energy X-ray absorptiometry (DXA) is accepted as a standard for diagnosing osteoporosis. Several databases are available for T-score calculation worldwide. Our aim was to compare hip bone mineral density (BMD) in young Estonian adults with the mean BMD in the National Health and Nutrition Examination Survey (NHANES) femur database and to compare the performance of these 2 databases. A population sample of 304 subjects was analyzed with a Lunar DPX-IQ DXA machine (GE Lunar Co., Madison, WI). Seventy-seven healthy young individuals were selected based on their age (25-39 yr). Their femur neck, trochanter, and total hip mean standardized BMD was compared with the corresponding data from the NHANES III database. Diagnostic agreement was assessed in a population sample of adults and in a clinical convenience sample from the densitometry unit. The BMD in the proximal femur in healthy young Estonian adults did not differ from the mean BMD in the NHANES subjects (p > 0.05). Differences in diagnosing osteoporosis and osteopenia are present if the Estonian reference database is used instead of the US standard database. Prospective studies with fracture data for assessing the predictive capability of these reference databases and the additional benefit of adding the FRAX (World Health Organization Collaborating Centre for Metabolic Bone Diseases, University of Sheffield, UK) tool to fracture prediction and osteoporosis diagnosis are needed in Estonia.

Seasonal variance of 25-(OH) vitamin D in the general population of Estonia, a Northern European country.

BACKGROUND: Vitamin D has a wide variety of physiological functions in the human body. There is increasing evidence that low serum levels of this vitamin have an important role in the pathogenesis of different skeletal and extra-skeletal diseases. Vitamin D deficiency and insufficiency is common at northern latitudes. There are few population-based studies in the northern European region looking at the issue in a wider age group. We aimed to measure Vitamin D level in the general population of Estonia (latitude 59 degrees N), a North-European country where dairy products are not fortified with vitamin D. METHODS: The study subjects were a population-based random selection of 367 individuals (200 women and 167 men, mean age 48.9 +/- 12.2 years, range 25-70 years) from the registers of general health care providers. 25-(OH) vitamin D (25(OH)D) level and parathyroid hormone (PTH) were measured in summer and in winter. Additionally age, sex, body mass index (BMI) and self-reported sunbathing habits were recorded. RESULTS: The mean serum 25(OH)D concentration in winter was 43.7 +/- 15 nmol/L and in summer 59.3 +/- 18 nmol/L (p < 0.0001). In winter 73% of the subjects had 25(OH)D insufficiency (25(OH)D concentration below 50 nmol/L) and 8% had deficiency (25(OH)D below 25 nmol/L). The corresponding percentages in summer were 29% for insufficiency and less than 1% for deficiency. PTH reached a plateau at around 80 nmol/L. BMI and age were inversely associated with 25(OH)D, but lost significance when adjusted for sunbathing habits. A difference in the seasonal 25(OH)D amplitude between genders (p = 0.01) was revealed. CONCLUSION: Vitamin D insufficiency is highly prevalent throughout the year in a population without vitamin D dairy fortification living at the latitude of 59 degrees N.

Splice variant IVS2-2A>G in the SLC26A5 (Prestin) gene in five Estonian families with hearing loss.

OBJECTIVE: The aim of our study was to identify the IVS2-2A>G sequence change in the SLC26A5 (Prestin) gene in Estonian individuals with hearing loss and in their family members. METHODS: In the years 2005-2007 we have screened 194 probands with early onset hearing loss and 68 family members with an arrayed primer extension (APEX) microarray, which covers 201 mutations in six nuclear genes (GJB2, GJB6, GJB3, GJA1, SLC26A4, SLC26A5) and two mitochondrial genes encoding 12S rRNA and tRNA-Ser (UCN). RESULTS: In four probands with early onset hearing loss and in five unaffected family members from five families we identified the IVS2-2A>G change in one allele of the SLC26A5 gene. We did not find any homozygosity for this splice variant. IVS2-2A>G was identified in 2.1% of probands. One of these probands, however, is also homozygous for the 35delG mutation in the GJB2 gene and a second patient has Down syndrome, which is also associated with hearing impairment. Therefore, in those two cases the etiology of the hearing loss is probably not associated with the IVS2-2A>G sequence change in the SLC26A5 gene. CONCLUSION: Our data support the hypothesis that heterozygosity for the mutation IVS2-2A>G in SLC26A5 gene may not, by itself, be sufficient to cause hearing loss.

Insulin Resistance in Early Rheumatoid Arthritis Is Associated with Low Appendicular Lean Mass.

In established rheumatoid arthritis (RA), the presence of insulin resistance (IR) is well proven but, in the early stage of the disease, data are inconclusive. We evaluated the presence of IR and associations with body composition (BC) parameters among early RA (ERA) and control subjects. The study group consisted of 92 ERA and 321 control subjects. Using homeostatic model assessment of IR (HOMA-IR), the cut-off value for IR was 2.15. 56% of the ERA patients and 25% of the controls had IR. Of the BC parameters, patients with early RA had less fat-free mass and appendicular lean mass (ALM). In multivariable model, ERA group (b-Coefficient) (4.8, CI: 2.6-8.8), male gender (7.7, CI: 2.7-22.1), and fat mass index (1.2, CI: 1.1-1.4) were associated with IR. Insulin-resistant ERA patients had higher inflammatory markers and higher disease activity. In the multivariable model in the ERA group, IR was associated with male gender (b-Coefficient) (7.4, CI: 153-34.9), high disease activity (6.2, CI: 1.7-22.2), and lower ALM (0.03, CI: 0.001-0.97). IR develops in the early stage of RA in the majority of patients. IR is more common among males and is associated with RA disease activity and lower ALM.

Selection of indicators for tonsillectomy in adults with recurrent tonsillitis.

BACKGROUND: We aimed to find some new indicators for tonsillectomy (TE) in adults with recurrent tonsillitis (RT) by exploring whether the frequency of tonsillitis episodes and the length of morbidity period are associated with the macroscopic signs of sclerotic process in tonsils and microbiological data assessed by culture, molecular (PCR) and transmission electron microscopy (EM) methods. METHODS: The study involved 62 RT patients admitted for TE (age range 15-35, median 22 years) and 54 healthy volunteers (age range 18-24, median 20 years). The index of tonsillitis (IT) was calculated by multiplying the number of tonsillitis episodes per year by the morbidity period in years. On oropharyngeal examination the presence or absence of three sclerotic signs was evaluated: tonsillar sclerosis, obstruction of tonsillar crypts and scar tissue on the tonsils. The occurrence of Streptococcus pyogenes was assessed by culture and PCR methods in 24 tonsillar core specimens. The samples for EM investigation of crypt epithelium were taken from 10 removed tonsils. RESULTS: The IT values were in positive correlation with the number of sclerotic signs on oropharyngeal examination (r = 0.325, P = 0.010). Based on the IT values and the presence or absence of tonsillar sclerosis and obstruction of tonsillar crypts the receiver-operating curve (ROC) was constructed. It revealed that an IT score of 36 is an optimal cut-off value for prediction of sclerotic type tonsils. S. pyogenes was never found by culture, but its presence by PCR in nearly one third (29%) of diseased tonsillar tissue specimens was tightly associated with longer morbidity. EM revealed coccoid forms of intracellular bacteria in the crypt epithelium, which was accompanied with the damage of tight junctions between epithelial cells. CONCLUSION: The index of tonsillitis > or = 36, being a combination between the frequency of tonsillitis and the length of morbidity period, predicts the sclerotic process in recurrently inflamed tonsils. Therefore, the high IT values could serve as an indicator for TE in adults. The correlation between the longer morbidity period and the presence of S. pyogenes by PCR suggests that persistent infection may have a role in maintenance of recurrent inflammation in tonsils.

Macroscopic oropharyngeal signs indicating impaired defensive function of palatine tonsils in adults suffering from recurrent tonsillitis.

The present study explored in adults suffering from recurrent tonsillitis the association between macroscopic oropharyngeal signs of recurrent inflammation, immunomorphology of palatine tonsils (counts of neutrophils by CD4 and macrophages by CD68 monoclonal antibodies in tonsillar microcompartments) and the occurrence of post-tonsillectomy bacteremia. The study involved 50 adults (31 females and 19 males) with recurrent tonsillitis. According to predominance of either inflammatory changes or evidence of sclerotic process in palatine tonsils and surrounding tissue macroscopic at oropharyngeal examination, the patients were divided into groups with 'inflammatory-type' and 'sclerotic-type' tonsils. Biochemically detected mean collagen content was significantly higher in 'sclerotic-type' tonsils than in 'inflammatory-type' tonsils (p=0.001). Post-tonsillectomy bacteremia was found in 22 patients (44%). A noteworthy finding was the higher recovery of anaerobes from blood cultures than in previous studies. A logistic regression analysis revealed that the post-tonsillectomy bacteremia was strongly associated with 'sclerotic-type' tonsils (p=0.0015) and with low counts of neutrophils in tonsillar tissue (p=0.047). We conclude that macroscopic oropharyngeal signs of sclerotic process in palatine tonsils indicate impaired tonsillar defense, in terms of lowered counts of neutrophils, increasing the risk of post-tonsillectomy bacteremia.