Bone geometry of the hip is associated with obesity and early structural damage – a 3.0 T magnetic resonance imaging study of community-based adults

IntroductionThe mechanism by which obesity increases the risk of hip osteoarthritis is unclear. One possibility may be by mediating abnormalities in bony geometry, which may in turn be associated with early structural abnormalities, such as cartilage defects and bone marrow lesions.MethodsOne hundred and forty one older adults with no diagnosed hip osteoarthritis had weight and body mass index measured between 1990 and 1994 and again in 2009 to 2010. Acetabular depth and lateral centre edge angle, both measures of acetabular over-coverage, as well as femoral head cartilage volume, cartilage defects and bone marrow lesions were assessed with 3.0 T magnetic resonance imaging performed in 2009 to 2010.ResultsCurrent body mass index, weight and weight gain were associated with increased acetabular depth and lateral centre edge angle (all P ≤ 0.01). For every 1 mm increase in acetabular depth, femoral head cartilage volume reduced by 59 mm³ (95% confidence interval (CI) 20 mm³ to 98 mm³, P < 0.01). Greater acetabular depth was associated with an increased risk of cartilage defects (odds ratio (OR) 1.22, 95% CI 1.03 to 1.44, P = 0.02) and bone marrow lesions (OR 1.29, 95% CI 1.01 to 1.64, P = 0.04) in the central region of the femoral head. Lateral centre edge angle was not associated with hip structure.ConclusionsObesity is associated with acetabular over-coverage. Increased acetabular depth, but not the lateral centre edge angle, is associated with reduced femoral head cartilage volume and an increased risk of cartilage defects and bone marrow lesions. Minimising any deepening of the acetabulum (for example, through weight management) might help to reduce the incidence of hip osteoarthritis.     

Early cartilage abnormalities at the hip are associated with obesity and body composition measures – a 3.0T MRI community-based study

IntroductionAlthough obesity is a risk factor for hip osteoarthritis (OA), the role of body composition, if any, is unclear. This study examines whether the body mass index (BMI) and body composition are associated with hip cartilage changes using magnetic resonance imaging (MRI) in community-based adults.Methods141 community-based participants with no clinical hip disease, including OA, had BMI and body composition (fat mass and fat free mass) measured at baseline (1990 to 1994), and BMI measured and 3.0 T MRI performed at follow-up (2009–2010). Femoral head cartilage volume was measured and femoral head cartilage defects were scored in the different hip regions.ResultsFor females, baseline BMI (β = −26 mm³, 95% Confidence interval (CI) -47 to −6 mm³, p = 0.01) and fat mass (β = −11 mm³, 95% CI −21 to −1 mm³, p = 0.03) were negatively associated with femoral head cartilage volume. Also, while increased baseline fat mass was associated with an increased risk of cartilage defects in the central superolateral region of the femoral head (Odds Ratio (OR) = 1.08, 95% CI 1.00–1.15, p = 0.04), increased baseline fat free mass was associated with a reduced risk of cartilage defects in this region (OR = 0.82, 95% CI 0.67–0.99; p = 0.04). For males, baseline fat free mass was associated with increased femoral head cartilage volume (β = 40 mm³, 95% CI 6 to 74 mm³, p = 0.02).ConclusionsIncreased fat mass was associated with adverse hip cartilage changes for females, while increased fat free mass was associated with beneficial cartilage changes for both genders. Further work is required to determine whether modifying body composition alters the development of hip OA.     

Pelizaeus-Merzbacher disease: identification of heterozygotes with magnetic resonance imaging?

Summary We report magnetic resonance imaging (MRI) findings in two obligate and four facultative carriers for the classical X-linked from of Pelizaeus-Merzbacher disease (PMD). In T2-weigthed images MR revealed bilateral multiple areas with signal hyperintensity in the periventricular and subcortical white matter in five women. Until suitable and closely linked DNA probes are found for heterozygote determination, MRI may represent a suitable means for carrier detection in individuals at risk in PMD families.Presented in part at the meeting (recent result session) of European Federation of Child Neurology Societies, June 1987, Hyvinkää, Finland, and the fall meeting of the Clinical Genetics Society, November 1987, London, UK     

Perinatal and early life risk factors for childhood brain tumors: Is instrument-assisted delivery associated with higher risk?

BackgroundThe childhood peak of brain tumors suggests that early-life exposures might have a role in their etiology. Hence, we examined in the Greek National Registry for Childhood Hematological Malignancies and Solid tumors (NARECHEM-ST) whether perinatal and early-life risk factors influence the risk of childhood brain tumors.MethodsIn a nationwide case-control study, we included 203 cases (0–14 years) with a diagnosis of brain tumor in NARECHEM-ST (2010–2016) and 406 age-, sex-, and center-matched hospital controls. Information was collected via interviews with the guardians and we analyzed the variables of interest in multivariable conditional logistic regression models.ResultsInstrument-assisted delivery was associated with higher (OR: 7.82, 95%CI: 2.18–28.03), whereas caesarean delivery with lower (OR: 0.67, 95%CI: 0.45-0.99) risk of childhood brain tumors, as compared to spontaneous vaginal delivery. Maternal alcohol consumption during pregnancy (OR: 2.35, 95%CI: 1.45–3.81) and history of living in a farm (OR: 4.98, 2.40–10.32) increased the odds of childhood brain tumors. Conversely, higher birth order was associated with lower risk (OR for 2nd vs. 1st child: 0.60, 95%CI: 0.40-0.89 and OR for 3^rd vs. 1^st: 0.34, 95%CI: 0.18-0.63). Birth weight, gestational age, parental age, history of infertility, smoking during pregnancy, allergic diseases, and maternal diseases during pregnancy showed no significant associations.ConclusionsPerinatal and early-life risk factors, and specifically indicators of brain trauma, exposure to toxic agents and immune system maturation, might be involved in the pathogenesis of childhood brain tumors. Larger studies should aim to replicate our findings and examine associations with tumor subtypes.     

A study of French centenarians: are ACE and APOE associated with longevity?

Association study is the method of choice to identify genes involved in complex processes that result from the interaction of environmental and genetic factors. However, because of biases that increase the risk of false positive reports, preliminary positive conclusions have to be reproduced on other populations to be validated as firm conclusions. In 1994, certain alleles of two genes, APOE (Apolipoprotein E) and ACE (angiotensin converting enzyme), were reported to be more frequent in French centenarians, suggesting an association with such a complex polyfactorial process as longevity. Enlargement of the French centenarian cohort allows a new assessment of this hypothesis on 563 centenarians. In contrast to APOE, the ACE association was not confirmed. Retrospective analysis of the initial study revealed discrepancies that may in part explain this observation. Risk of reporting false positive associations is discussed and recommendations to set up a rigorous experimental design are proposed.     

Nucleolar organizer region heteromorphism associated with trisomy-21: a risk factor for non-disjunction?

An unusual nucleolar organizer region (double NOR) on chromosome 13 was observed in a Down syndrome child [47, XY, +21, dNOR(13)]. The variant chromosome was inherited from the mother [46, XX, dNOR(13)]. The extra chromosome 21 in the proband was maternal origin. The frequency of NOR chromosome association showed relatively high frequency in the mother and proband as compared to the controls. The result suggest that chromosome variants involving extra copies of NOR may indeed be involved in the meiotic nondisjunction of chromosome-21.     

Evaluation of extracorporeal shock wave therapy for refractory angina pectoris with quantitative analysis using cardiac magnetic resonance imaging: a short communication

Aims

There is a continuing search for new treatment options in patients who suffer from refractory angina pectoris to improve quality of life. Several studies have recently demonstrated promising results by stimulating angiogenesis using extracorporeal shockwave therapy in these patients. The purpose of this study is to quantitatively analyse the effect of extracorporeal shockwave therapy on myocardial perfusion in patients with refractory angina pectoris.

Methods

We included 15 patients with NYHA class 3–4 of whom 8 patients underwent baseline and follow-up cardiac magnetic resonance imaging (CMR). All patients received 9 shockwave treatments of their ischaemic zone over a period of 3 months.

Results

Quantitative analysis of myocardial perfusion using CMR revealed no significant improvement of myocardial perfusion after treatment (0.80 ± 0.22 vs 0.76 ± 0.31; p = 0.42). However, the total group of 15 patients did experience a significant improvement in NYHA class (p = 0.034) and reduction of nitroglycerin use (p = 0.012).

Conclusion

Although treatment with extracorporeal shockwave was associated with an improvement in NYHA class, we could not observe an improvement in myocardial ischaemic zone and perfusion with CMR. To unravel the exact mechanisms of shockwave treatment, more in vitro and animal studies as well as larger (placebo-controlled) studies are required.

     

Association of interleukin-6 and transforming growth factor-β1 gene polymorphisms with developmental hip dysplasia and severe adult hip osteoarthritis: a preliminary study

Developmental hip dysplasia (DDH) greatly contributes to occurrence of severe hip osteoarthritis (OA) in adulthood, but the association between the two is not a perfect one. Both conditions are known to have a strong genetic component. Transforming growth factor β1 (TGF-β1) and interleukin-6 (IL-6) are two pro-inflammatory cytokines included in pathogenesis of OA, bone remodeling and development of bone and joint tissues. TGF-β1 gene has a polymorphic site in the signal sequence ((29)T→C) and "C allele carriage" is associated with higher circulating TGF-β1 levels. IL-6 gene has several polymorphic sites in the promoter region including -572T→C transition associated with higher circulating IL-6 levels. As a preliminary investigation on possible association between these polymorphisms and severe adult hip OA secondary to DDH, 28 consecutive patients and 20 healthy controls were genotyped at these loci. With adjustment for sex, "C allele carriage" in the TGF-β1 signal sequence and CC genotype ("transition homozygous") at locus -572 in the IL-6 promoter were each associated with severe OA secondary to DDH (OR=13.4, p=0.016 and OR=6.2, p=0.024, respectively). The combination of these genotypes was particularly strongly associated with the disease (OR=11.1, p<0.001). Data support feasibility of larger-scale studies on potential association between TGF-β1 signal sequence and IL-6 promoter polymorphisms and occurrence of DDH and (un)related severe OA.     

Three single nucleotide variants of the HDAC gene are associated with type 2 diabetes mellitus in a Chinese population: A community-based case–control study

Objectives

There are no data regarding the possible role of the single nucleotide polymorphism (SNP) of class I histone deacetylases (HDACs) in type 2 diabetes mellitus (DM). We designed this study to examine whether polymorphisms of HDACs can be implicated in that disease.

Methods

A community-based, case–control study was conducted, with a total of 568 subjects (284 patients and 284 controls) enrolled. Four polymorphisms of HDAC1 (rs1741981) and HDAC3 (rs11741808, rs2547547, rs2530223) were examined by the use of TaqMan technology.

Results

We found a significant association with risk of type 2 DM for three SNPs of HDAC3, including rs11741808 [odds ratio (OR) = 0.53, 95% confidence interval (CI): 0.35–0.81], rs2547547 [OR = 1.72, 95% CI: 1.13–2.64], and rs2530223 [OR = 1.39; 95% CI: 1.01–1.91]. Subgroup analysis showed that BMI ≥ 23 kg/m², high triglyceride and high blood pressure, together with the rs11741808AG genotype, were associated with a significantly decreased risk for type 2 DM, with ORs of 0.50 (95% CI: 0.27–0.91), 0.38 (95% CI: 0.20–0.71) and 0.43 (95% CI: 0.24–0.76) compared with the AA genotype, respectively. In a population with normal total cholesterol, the AG genotype yielded a significantly decreased risk of type 2 DM risk, with an OR of 0.42 (95% CI: 0.25–0.70) when compared with the persons of the AA genotype. For rs2547547, in a population with normal total cholesterol and triglyceride, the AG genotype was associated with a significantly increased risk of type 2 DM, with ORs of 1.92 (95% CI: 1.17–3.15) and 2.24 (95% CI: 1.28–3.94) when compared with the population carrying the AA genotype.

Conclusions

The results suggest that variants of HDAC3 contribute to an increased prevalence of type 2 DM in the Chinese Han population.     

IκBα polymorphisms were associated with increased risk of gastric cancer in a southern Chinese population: a case-control study

AimNuclear factor-kappa B inhibitor alpha (IκBα) polymorphisms were found to be associated with inflammatory diseases. However, the association between IκBα polymorphisms with gastric cancer is still unknown. We aim to investigate the association between IκBα polymorphisms and gastric cancer risk in a large population-based case–control study among southern Chinese.Main methodsA population-based case–control study was conducted between 1999 and 2006 in Guangdong Province, China. A total of 1010 gastric cancer patients and 1500 healthy controls were enrolled in this study. IκBα polymorphisms were identified by sequencing of IκBα gene ranging from the 2 kb promoter region to the 3.5 kb genomic region. Polymorphisms in IκBα were analyzed by TaqMan SNP genotyping assay.Key findingsrs17103265 deletion homozygote (?/?) had significantly increased gastric cancer risk (OR = 2.11, 95% CI = 1.17–3.83, P = 0.01), compared with rs17103265 T homozygote (TT). rs17103265 (?/?) genotype was significantly associated with increased risk of intestinal-type gastric cancer with (OR = 2.21, 95% CI = 1.19–4.08, P = 0.01), but not with the diffuse or mix type of gastric cancer. rs17103265 (?/?) was associated with poorly differentiated gastric cancer (OR = 2.05, 95% CI = 1.07–3.94, P = 0.03), but not with moderately or well differentiated gastric cancer. A significant decrease in luciferase activity was observed in rs17103265 deletion allele as compared with the vector containing the rs17103265 T allele (P < 0.0001). rs17103265 polymorphism was not associated with the prognosis of gastric cancer patients.SignificanceIκBα rs17103265 deletion homozygote is a novel genetic risk factor for gastric carcinogenesis, especially for the development of certain subtypes of gastric cancer in southern Chinese population.     

Haplotypes within genes of β-chemokines in 17q11 are associated with multiple sclerosis: a second phase study

We previously defined haplotypes of single nucleotide polymorphisms (SNP) with possible relevance to multiple sclerosis (MS) in 2 CC chemokine ligand (CCL) clusters in chromosome 17q11. The 17q11 region was also identified as a susceptibility locus by a meta-analysis of linkage studies. To confirm and refine the previous finding in a second, high resolution SNP scan in a new set of families. We genotyped 232 SNPs in 1369 individuals in 361 MS families. Transmission of marker alleles and haplotypes from unaffected parents to affected offspring was tested by using the pedigree disequilibrium test, the TRANSMIT 2.5 program, and the family and haplotype based association tests. Distribution of linkage disequilibrium (LD) was assessed by ldmax. In consensus with observations in the first scan, the present study identified haplotypes within CCL3 and CCL15 in the telomeric CCL cluster. There was also an overlap in the findings in the centromeric CCL cluster. Strong and extensive LD was detected both within the centromeric and telomeric CCL gene clusters. The present study replicates our previous findings and further suggests the existence of MS associated haplotypes within genes of CCL3 and CCL15. Haplotypes of interest are also present within the centromeric gene cluster (including CCL2, CCL7, CCL11, CCL8, and CCL13), but extensive LD prevents further refinement of these haplotypes by using the methods applied. Sequencing of the identified chromosomal segments and their flanking regions will be necessary to define specific variants with direct relevance to MS pathogenesis.     

Vascular endothelial growth factor 1498C/T, 936C/T polymorphisms associated with increased risk of colorectal adenoma: a Chinese case–control study

Single nucleotide polymorphisms in vascular endothelial growth factor gene VEGF, 1498C/T and 936 C/T are associated with colorectal cancer. We sought to determine whether such genetic variability in VEGF contributes to susceptibility of colorectal adenoma (CRA), a presumably precancerous state of colorectal cancer. In this research, two aforementioned polymorphisms were investigated for CRA susceptibility in a Chinese case–control study. The epidemiological risk factors were collected through questionnaire. The plasma VEGF levels were measured via enzyme-linked immunosorbent assay (ELISA). The Taqman-Probe assay was used to determine genotypes in 224 CRA patients and 200 CRA-free controls. The clinicopathological data of each sample were collected for further correlation analysis. According to data analysis males, cigarette smokers, patients who carry metabolic syndrome or familial antecedent of adenomas were significantly associated with CRA risk. Plasma VEGF levels of CRA patients were higher than those of controls (P = 0.003). This difference is independent of genotypes. The carriers with 936CT and CT+TT had higher risk of CRA in comparison with controls (CT vs. CC, OR 2.00, 95% CI 1.23–3.25, P = 0.006; CT+TT vs. CC, OR 2.04, 95% CI 1.28–3.26, P = 0.003). 936-T allele was associated with increased risk of CRA (OR 1.91, 95% CI 1.25–2.91, P = 0.003). Both CRA and control show no difference in the genotype of 1498C/T and the allele frequency of C−/T−. CRA patients with haplotype 1498T+936T presented significantly higher risk than those with wild-type 1498T+936C. Moreover, patients carrying 936CT+TT and 936-T allele demonstrated a tendency for villous adenoma. CRA patients have elevated plasma VEGF levels. The VEGF 936C/T polymorphism and 1498T+936T haplotype were found to be associated with increased CRA susceptibility.     

Serum p53 protein and anti-p53 antibodies are associated with increased cancer risk: a case–control study of 569 patients and 879 healthy controls

The aim of this study to determine whether serum p53 protein and antibodies are associated with malignant tumors. A case–control study was conduct in 569 patients with various types of malignant tumors and 879 healthy controls. Serum p53 protein and antibodies were analyzed by enzyme-linked immunosorbent assay (ELISA).The rate of positive p53 protein in patients with various malignant tumors was 4.22% compared with 0.34% in healthy controls (P < 0.001). The rate of anti-p53 antibodies in patients with various malignant tumors was 14.59% compared with 1.02% in healthy controls (P < 0.001). The adjusted odd ratio (OR) for p53 protein was 17.55 (95% CI = 4.98–61.94). The adjusted odd ratio for anti-p53 antibodies was 14.27 (95% CI = 6.75–30.16). The study strongly suggested that serum p53 protein and antibody are associated with increased cancer risk and can be used as early serological markers in the diagnosis of malignancies tumors.     

Body mass index and weight gain after middle adulthood are associated with risk of papillary thyroid cancer: A case–control study

BackgroundIt is unclear whether weight change after middle adulthood influences the risk of thyroid cancer. The aim of this study was to investigate associations between the risk of papillary thyroid cancer (PTC) and body mass index (BMI) and weight change after middle adulthood (age 35).MethodsA matched case–control study based on three hospitals included 516 pairs of cases newly diagnosed with PTC and controls. Current height and weight after defecation in the morning were measured by trained nurses. During measurement, all subjects were requested to wear lightweight clothing and no shoes. Weight at age 35 was self-reported. BMI and weight change were modeled as continuous and categorical variables. Conditional and unconditional logistic regression models were used to estimate the odds ratio (OR) and 95% confidence interval (95%CI) for the association between BMI and weight change after middle adulthood and PTC.ResultsAfter adjustment for covariates, measured BMI at the time of current diagnosis was positively associated with PTC (OR 1.16, 95%CI 1.10–1.21). According to WHO BMI guidelines for Asia-Pacific populations, the OR (95%CI) for PTC risk in obesity was 2.99 (1.92–4.67) compared to normal weight (p-trend <0.001). Moreover, PTC was positively associated with BMI at age 35; the OR (95%CI) for PTC risk per unit increase in BMI was 1.06 (1.02–1.11). Compared to stable weight (changed <0.5 kg/year), weight gain ≥1.0 kg/year after middle adulthood was positively associated with PTC (OR 2.57, 95%CI 1.39–4.76, p-trend <0.001). Compared to maintaining non-overweight status, the PTC risk was significantly increased in those individuals who gained weight and became overweight after middle adulthood (OR 3.82, 95%CI 2.50–5.85).ConclusionThis study showed that high BMI and obesity were positively associated with increased risk of PTC, and weight gain after middle adulthood also could elevate the PTC risk.     

A combined nuclear magnetic resonance and molecular dynamics study of the two structural motifs for mixed-linkage β-glucans: methyl β-cellobioside and methyl β-laminarabioside

The conformational and hydration properties of the two disaccharides methyl β-cellobioside and methyl β-laminarabioside were investigated by NMR spectroscopy and explicit solvation molecular dynamics simulations using the carbohydrate solution force field (CSFF). Adiabatic maps produced with this force field displayed 4 minima A: (Φ = 300°, Ψ = 280°), B: (Φ = 280°, Ψ = 210°), C: (Φ = 260°, Ψ = 60°), and D: (Φ = 60°, Ψ = 260°) for methyl β-cellobioside and 3 minima A: (Φ = 290°, Ψ = 130°), B: (Φ = 270°, Ψ = 290°), and C: (Φ = 60°, Ψ = 120°) for methyl β-laminarabioside. Molecular dynamics simulations were initiated from all minima. For each disaccharide, the simulation started from the A minimum was conducted for 50 ns, while the other minima were explored for 10 ns. The simulations revealed two stable minima for both compounds. For methyl β-cellobioside, the simulation minima in aqueous solution were shifted from their adiabatic map counterparts, while the simulation minima for methyl β-laminarabioside coincided with the corresponding adiabatic map minima. To validate the simulation results, NMR-derived NOEs and coupling constants across the glycoside linkage, ³J_HC and ³J_CH, were compared with values calculated from the MD trajectories. For each disaccharide, the best agreement was obtained for the simulations started at the A minimum. For both compounds, inter-ring water bridges in combination with the direct hydrogen bonds between the same groups were found to be determining factors for the overall solution structure of the disaccharides which differed from solid-state structures. Comparison with helical parameters showed that the preferred glycosidic dihedral configurations in the methyl β-cellobioside simulation were not highly compatible with the structure of cellulose, but that curdlan helix structures agreed relatively well with the methyl β-laminarabioside simulation. Polymers generated using glycosidic dihedral angles from the simulations revealed secondary structure motifs that that may help to elucidate polymer associations and small-molecule binding.     

Impaired modulation of circadian rhythms in patients with diabetes mellitus: a risk factor for cardiac thrombotic events?

Serious adverse cardiovascular events, including myocardial infarction, sudden cardiac death, and stroke, frequently result from rupture of atherosclerotic plaques with superimposed thrombosis and exhibit a pronounced circadian rhythmicity, peaking in the morning hours. Two potentially synergistic mechanisms play a pathogenic role in the circadian variation of arterial thrombotic events. A morning surge in sympathetic activity alters hemodynamic forces and predisposes vulnerable coronary atherosclerotic plaques to rupture. Day-night variations of hemostatic and fibrinolytic factors result in morning hypercoagulability and hypofibrinolysis, promoting intraluminal thrombus formation at the same time when the risk for plaque rupture is highest. Diabetic patients have a very high cardiac event rate but fail to show normal circadian fluctuations in the occurrence of myocardial infarction. Alterations in the circadian variation autonomic tone, blood pressure, and the thrombotic-thrombolytic equilibrium have been documented in diabetic patients. These include reduced or absent 24-h periodicity in autonomic tone, fibrinolytic activity, and thrombotic tendency, and a blunted decline in nocturnal blood pressure. Disruption of these circadian rhythms explains the lack of significant circadian distribution of cardiac events in diabetic patients. Moreover, the loss of these normal biorhythms results in a continuous susceptibility to thrombotic events throughout the day and may contribute to the excess cardiovascular mortality and morbidity in these patients. (Chronobiology International, 18(1), 109-121, 2001)     

Low numbers of blood and salivary natural killer cells are associated with a better response to belimumab in primary Sj?gren’s syndrome: results of the BELISS study

IntroductionIn this study, we sought to address changes in blood lymphocyte subpopulations and labial salivary gland (LSG) inflammation after belimumab treatment in patients with primary Sjögren’s syndrome (pSS) and to identify predictors of response to treatment.MethodsSequential blood lymphocyte subsets and LSG biopsies were analysed between week 0 (W0) and W28 in 15 patients with pSS treated with belimumab. Systemic response to treatment was defined as a decrease in the European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index score of ≥3 points at W28.ResultsAfter belimumab, we observed a decrease in blood B lymphocytes primarily involving CD27-negative/immunoglobulin D–positive naïve B cells (p=0.008). Lymphocytic sialadenitis (focus score >1) that was present in 12 patients (80.0 %) before belimumab treatment became negative in 5 of them after treatment (p=0.03). The median (interquartile range) LSG B-cell/T-cell ratio decreased from 0.58 (0.5–0.67) to 0.50 (0.5–0.5) (p=0.06). B-cell activating factor (BAFF) staining was detected in 11 (78.6 %) of 14 patients before belimumab treatment compared with 7 (50.0 %) of 14 after belimumab therapy (p=0.10). The median percentage of BAFF-positive cells in foci significantly decreased from 27.5 % (10–40) to 5 % (0–20) (p=0.03). A systemic response was achieved in six patients (40 %). The only predictor of response was the presence of a low number of natural killer (NK) cells, both in blood (8.5 % [7–10] vs 11 % [9–21]; p=0.04) and in LSG (20.6/mm³ [20.0–21.4] vs 30.0/mm³ [25.0–100.0], p=0.003). Serum BAFF levels did not influence response to treatment.ConclusionsLow blood and salivary NK cell numbers are associated with a better response to belimumab. This suggests that two distinct subsets of pSS may exist: one with a predominant type I interferon (IFN)–BAFF–B-cell axis, representing good responders to belimumab; and one with a predominant type II IFN–NK cell axis, representing non-responders.

Trial registration

ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT01160666","term_id":"NCT01160666"}}NCT01160666. Registered 9 July 2010.     

Clinical variables predicting the risk of a hospital stay for longer than 7 days in patients with severe acute exacerbations of chronic obstructive pulmonary disease: a prospective study

Background

Chronic obstructive pulmonary disease (COPD) patients may experience an acute exacerbation (AECOPD) that requires hospitalisation. The length of hospital stay (LHS) has a great economic impact on the health-care system. Knowing the predictors of prolonged LHS could help to identify possible interventions.

Methods

We performed a prospective study to identify the clinical predictors of prolonged LHS in patients hospitalised for AECOPD. We divided the study sample by LHS into normal (≤7?days) and prolonged LHS (>?7?days) groups. Outcomes were the need for non-invasive and invasive mechanical ventilation (NIMV and IMV), intensive care unit (ICU) admission, and the 3-year mortality.

Results

We enrolled 437 patients, of which 213 and 224 had normal LHS and prolonged LHS, respectively. Patients with a prolonged LHS had more prior hospitalisations for AECOPD, a worse mMRC (modified Medical Research Council) dyspnoea score, a higher prevalence of long-term oxygen therapy and a higher rate of congestive heart disease. During the current admission, this group also tended to require NIMV, IMV and ICU admission and the mortality risks at 6?months, 1?year and 3?years were higher. In the multivariate regression analysis, an mMRC dyspnoea score?≥?2 (odds ratio-OR 2.24; 95% confidence interval-CI 1.34 to 3.74; p?=?0.002) and the presence of acute respiratory acidosis (OR 2.75; 95% CI 1.49 to 5.05; p?=?0.001) predicted a prolonged LHS at admission.

Conclusions

The presence of an mMRC ≥2 and acute respiratory acidosis at admission independently increased the risk of a prolonged LHS for AECOPD.