Low rate of new-onset primary biliary cholangitis in a cohort of anti-mitochondrial antibody-positive subjects over six years of follow-up.

BACKGROUND AND AIMS: Anti-mitochondrial antibodies (AMA) are closely linked to primary biliary cholangitis (PBC). The prevalence of AMA in the general population is low, and AMA positivity may precede PBC. We aimed to determine the natural history of subjects with positive AMA. METHODS: In total, 302 patients were tested AMA-positive over a ten-year period. Of these, immunoblotting confirmed specific AMA in 184 (29 male, 155 female, age 59.6 ± 14.1 years). These subjects were invited to our liver outpatient clinic for clinical and biochemical re-evaluation. Detailed clinical history data were additionally collected from the hospital computer system and by telephone. The subsequent course with regard to mortality, liver-related morbidity, extrahepatic co-morbidities and effectiveness of PBC treatment was determined in 150 subjects (81.5%). RESULTS: After 5.8 ± 5.6 years of follow-up (FU), of 184 AMA-positive subjects, 28 subjects (15.2%; liver-related mortality n = 5) were deceased, and 122 subjects (66.3%) completed FU while 34 subjects (18.5%) were not available for FU. The 122 patients who completed FU were 63 patients with established PBC, six de novo cases of PBC (10.2% of 59 initially at risk), 42 (34.4%) subjects were still AMA-positive without PBC, and 11 (9.0%) subjects were AMA-negative at FU. CONCLUSIONS: Anti-mitochondrial antibodies-positive patients without PBC at baseline infrequently developed PBC over six years of FU. AMA positivity represented a transient serological autoimmune phenomenon in a significant proportion of subjects.

Clinical and metabolic characterization of obese subjects without non-alcoholic fatty liver: A targeted metabolomics approach.

INTRODUCTION: As a small proportion of obese individuals do not develop metabolic complications and non-alcoholic fatty liver disease (NAFLD), this study aimed to provide a comprehensive clinical, metabolic and genetic description of obese subjects with healthy livers. METHODS: A total of 183 subjects were stratified, according to BMI, presence of metabolic syndrome, biochemical liver tests and hepatic steatosis on ultrasound, into: (i) lean controls (n = 69); (ii) obese healthy (n = 50); and (iii)obese NAFLD (n = 62) groups. Detailed clinical, genetic and metabolic evaluations were then performed. RESULTS: Obese healthy subjects did not differ in glucose parameters from lean controls, and had a lower rate of minor TM6SF2 gene variants compared with obese NAFLD (2/49 vs. 11/60, respectively; P = 0.035) and lean controls (13/64; P = 0.035), but significantly higher leptin concentrations than lean controls (P < 0.001); they also higher adiponectin concentrations (P < 0.001), and lower TNF-α and IL-6 concentrations (P = 0.01 and P < 0.001, respectively), than obese NAFLD subjects. Also, metabolomic studies identified ether- and ester-containing phospholipids [PC ae C44:6, PC ae C42:5, PC aa C40:4; P < 0.001, corrected by the false discovery rate (FDR) method] and found that the amino-acids lysine, glycine and isoleucine (FDR < 0.001) differed between the two obese groups, but not between lean controls and obese healthy subjects. CONCLUSION: Obese people with healthy livers are characterized by intact glucose homoeostasis, lower pro-inflammatory cytokine levels, and higher adiponectin and leptin concentrations compared with obese people with NAFLD. In addition, the major allele of TM6SF2, a set of phosphatidylcholines and several amino acids are associated with healthy livers in obesity.

Adjustments of muscle capillarity but not mitochondrial protein with skiing in the elderly.

Downhill skiing in the elderly increases maximal oxygen uptake (VO2max) and carbohydrate handling, and produces muscle hypertrophy. We hypothesized that adjustments of the cellular components of aerobic glucose combustion in knee extensor muscle, and cardiovascular adjustments, would increase in proportion to VO2max. Nineteen healthy elderly subjects (age 67.5 ± 2.9 years) who completed 28.5 days of guided downhill skiing over 3 months were assessed for anthropometric variables, cardiovascular parameters (heart rate, hematocrit), VO2max, and compared with controls (n = 20). Biopsies of vastus lateralis muscle were analyzed for capillary density and expression of respiratory chain markers (NDUFA9, SDHA, UQCRC1, ATP5A1) and the glucose transporter GLUT4. Statistical significance was assessed with a repeated analysis of variance and Fisher's post-hoc test at a P value of 5%. VO2max increased selectively with ski training (+7 ± 2%). Capillary density (+11 ± 5%) and capillary-to-fiber ratio (12 ± 5%), but not the concentration of metabolic proteins, in vastus lateralis were increased after skiing. Cardiovascular parameters did not change. Fold changes in VO2max and capillary-to-fiber ratio were correlated and were under genetic control by polymorphisms of the regulator of vascular tone, angiotensin converting enzyme. The observations indicate that increased VO2max after recreational downhill ski training is associated with improved capillarity in a mainly recruited muscle group.

Gender- and site-specific differences of colorectal neoplasia relate to vitamin D.

BACKGROUND: The effect of vitamin D on colorectal adenomas may vary with regard to gender, localisation and histological type of the lesion. AIM: To define the role of vitamin D and gender in a Caucasian cohort of subjects undergoing screening colonoscopy after consideration of established risk factors. METHODS: One thousand five hundred and thirty-two subjects (813 males, 58.8 ± 9.7 years; 719 females, 59.7 ± 10.7 years) were allocated to tertiles of 25-hydroxyvitamin D3 [25(OH)D3 ] serum concentrations. The number, localisation, size and histology of the detected colonic lesions were recorded. RESULTS: Among men, no association was found between vitamin D and the total number, size and histological stage of adenomas at any site. In female subjects, less women with adenomas were found in the highest vitamin D tertile (N = 42/239; 17.2%) as compared to the low vitamin D group (N = 60/240; 25.0%; P = 0.035). In particular, the number of women with adenomas in the proximal colon was significantly lower in the highest tertile (N = 21/239, 8.8%) compared to the low vitamin D group (N = 41/240; 17.1%; P = 0.007). The rates at other sites were not different. The inverse association of vitamin D serum concentrations with the presence of adenomas in the proximal colon was maintained after adjustment for potential confounders. In 80 women on vitamin D supplementation, the rate of adenomas was lower compared to those not on supplementation (3/80; 3.8%; vs. 90/719; 12.5%; P = 0.016). CONCLUSIONS: A potential preventive effect of vitamin D on colorectal adenomas was found in the proximal colon in women. This observation is supported by further decrease of lesions in the proximal colon of women on vitamin D supplementation.

[Rare cause of knee pain after total knee arthroplasty]. / Seltene Knieschmerzursache nach Knietotalendoprothesenimplantation.

A painful knee after total knee arthroplasty may have various causes. In addition to commonly occurring causes, such as infections, aseptic loosening, implant failure or typical anterior knee pain, rare causes also have to be taken into account. We report a previously unknown cause of knee pain after total knee replacement involving a non-resected medial meniscus, which was sandwiched between the medial condyle of the femur and the inlay of the prosthesis and caused pain typical for a medial meniscus. After arthroscopic meniscectomy the patient was symptom-free.

[Aerobic and strength training in patients with diabetes mellitus type 2 and heart failure]. / Ausdauer- und Krafttraining bei Patienten mit Diabetes mellitus Typ 2 und Herzinsuffizienz.

Patients with type 2 diabetes mellitus and heart failure represent a relevant population in everyday practice. Several exercise training studies have documented numerous positive changes in cardiovascular risk factors, morbidity and mortality, that can only be achieved through long-term training programs of combined aerobic and strength training. This efficient and cost effective therapy should be offered to as many patients in need as possible.

Physical exercise through mountain hiking in high-risk suicide patients. A randomized crossover trial.

OBJECTIVE: The following crossover pilot study attempts to prove the effects of endurance training through mountain hiking in high-risk suicide patients. METHOD: Participants (n = 20) having attempted suicide at least once and clinically diagnosed with hopelessness were randomly distributed among two groups. Group 1 (n = 10) began with a 9-week hiking phase followed by a 9-week control phase. Group 2 (n = 10) worked vice versa. Assessments included the Beck Hopelessness Scale (BHS), Beck Depression Inventory (BDI), Beck Scale of Suicide Ideation (BSI), and maximum physical endurance. RESULTS: Ten participants of Group 1 and seven participants of Group 2 completed the study. A comparison between conditions showed that, in the hiking phase, there was a significant decrease in hopelessness (P < 0.0001, d = -1.4) and depression (P < 0.0001, d = -1.38), and a significant increase in physical endurance (P < 0.0001, d = 1.0), but no significant effect for suicide ideation (P = 0.25, d = -0.29). However, within the hiking phase, there was a significant decrease in suicide ideation (P = 0.005, d = -0.79). CONCLUSION: The results suggest that a group experience of regular monitored mountain hiking, organized as an add-on therapy to usual care, is associated with an improvement of hopelessness, depression, and suicide ideation in patients suffering from high-level suicide risk.

Salzburg Skiing for the Elderly Study: influence of alpine skiing on aerobic capacity, strength, power, and balance.

Alpine skiing is a recreational sport with high demands on the cardiovascular and neuromuscular systems. It is assumed that skiing could have positive effects on the decline in aerobic capacity, strength, and balance ability of older individuals. In a 12-week intervention study, 47 elderly subjects (age 60-76 years) were randomized into an intervention group (IG) and a control group (CG). The IG averaged 28.5 days of guided skiing during 12 weeks. Aerobic capacity, leg power, and strength as well as postural stability were tested before, immediately after, and 10 weeks after the intervention phase. VO(2 max) improved by 7.2% from Pre to Post for the IG, without any change in the CG. Jump height increased on average by 6% over the 12 weeks for the IG, while jump height for the CG deteriorated by -11.7%. Dynamic maximal strength measured in both legs increased by 16% in the IG during the 12 weeks of skiing. In the CG, it increased by 7%, without being significant. In postural ability, no differences between groups or over time were noted. It appears that, in older individuals, 12 weeks of skiing leads to a significant increase in aerobic capacity, leg muscle power, and strength.

Effect of alpine skiing training on tendon mechanical properties in older men and women.

Strain is one of the parameters determining tendon adaptation to mechanical stimuli. The aim of this study was to test whether the patellar tendon strain induced during recreational alpine skiing would affect tendon mechanical properties in older individuals. Twenty-two older males and females (67 ± 2 years) were assigned to a 12-week guided skiing programme (IG) and 20 aged-matched volunteers served as controls (CG). Patellar tendon mechanical properties and cross-sectional area (CSA) were measured before and after training, with combined dynamometry and ultrasonography scanning. None of the variables changed significantly in the CG after training. In the IG, tendon stiffness and Young's modulus were increased (respectively, 14% and 12%, P<0.01), without any significant change in tendon CSA. In addition, changes in tendon stiffness were blunted in women (9%) compared with men (19%). Serum IGF-1 concentration tended to be lower in women (-19%, P=0.07). These results demonstrate that the mechanical stimulus induced by alpine skiing is sufficient to elicit adaptive changes in patellar tendon mechanical and material properties in older subjects. Furthermore, the present sex-specific adaptations are consistent with previous reports of lower collagen metabolic responsiveness in women and may be underpinned by anthropometric and metabolic differences.

Salzburg Skiing for the Elderly Study: changes in cardiovascular risk factors through skiing in the elderly.

Numerous studies have shown that treatment of the modifiable cardiovascular risk factors (CVRF) results in a decreased risk to suffer from stroke or myocardial infarction. Despite the fact that exercise training is a potent treatment choice for CVRF, this is the first randomized study to assess the effects of alpine skiing on CVRF in elderly skiers. Subjects (n=42) were randomized into an intervention group (IG; n=22; 12 males/10 females; age: 66.6 ± 2.1 years) completing 12 weeks of guided skiing or a control group (CG; n=20; 10 males/10 females; age: 67.3 ± 4.4 years). CVRF were assessed before and after the intervention period. No cardiovascular event occurred within a total of 795.1 h of skiing. A significant increase in exercise capacity in IG (ΔVO(2 max) : +2.0 mL/kg/min, P=0.005) but not in CG (ΔVO(2 max) : -0.1 mL/kg/min, P=0.858; IG vs CG: P=0.008) as well as a decrease in body fat mass [IG: -2.3%, P<0.0001; CG: ± 0.0%, P=0.866; IG vs CG: P<0.0001] was achieved. Blood pressure, blood lipids, heart rate and everyday physical activity remained essentially unchanged. Alpine skiing in the elderly is safe with respect to cardiovascular events, and improves some, but not all CVRF.

Glucose homeostasis and cardiovascular disease biomarkers in older alpine skiers.

Alpine skiing and ski training involves elements of static and dynamic training, and may therefore improve insulin sensitivity. Healthy men and women who where beginners/intermediate level of alpine skiing, were studied before (Pre) and immediately after (Post) 12 weeks of alpine ski training. After an additional 8 weeks a third test (retention study, Ret) was performed. The subjects were randomized into an intervention group (IG, n=22, age=66.6 ± 0.4 years) or a control group (CG, n=20, age=67.0 ± 1.0 years). Plasma glucose decreased (P<0.05) in CG, but increased (P<0.05) again at Ret, while a continued decrease was seen in IG (Ret vs Post, P<0.05). Plasma insulin decreased (P<0.05) with training in IG, while no effect was seen in CG. HOMA2 index for insulin resistance decreased (P<0.05) from 0.80 ± 0.08 to 0.71 ± 0.09 in IG. The value at Ret (0.57 ± 0.08) tended (P=0.067) to be different from Post. In CG the corresponding values were 0.84 ± 0.09, 0.81 ± 0.12 and 0.70 ± 0.09, respectively. Total cholesterol and LDL decreased in both IC and CG, a result, interpreted as seasonal variation. Biomarkers for endothelial function and low-grade inflammation were not elevated and similar in IG and CG, and did not change. Alpine ski training improves glucose homeostasis and insulin sensitivity in healthy, elderly individuals.