A relationship between spinal new bone formation in ankylosing spondylitis and the sonographically determined Achilles tendon enthesophytes

Spinal new bone formation is a major but incompletely understood manifestation of ankylosing spondylitis (AS). We explored the relationship between spinal new bone formation and ultrasound (US)-determined Achilles enthesophytes to test the hypothesis that spinal new bone formation is part of a generalized enthesis bone-forming phenotype. A multicenter, case control study of 225 consecutive AS patients and 95 age/body mass index (BMI) matched healthy controls (HC) was performed. US scans of Achilles tendons and cervical and lumbar spine radiographs were obtained. All images were centrally scored by one investigator for US and one for radiographs, blinded to medical data. The relation between syndesmophytes (by modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) and the number of syndesmophytes) and enthesophytes (with a semi-quantitative scoring of the US findings) was investigated. AS patients had significantly higher US enthesophyte scores than HCs (2.1(1.6) vs. 1.6(1.6); p = 0.004). The difference was significant in males (p = 0.001) but not in females (p = 0.5). The enthesophyte scores significantly correlated with mSASSS scores (ρ = 0.274, p < 0.0001) with the association even stronger in males (enthesophyte scores vs. mSASSS ρ = 0.337, p < 0.0001). In multiple regression analysis, age, BMI, enthesophyte scores and disease duration were significantly associated with syndesmophytes in males, and keeping all other variables constant, increasing US enthesophyte scores increased the odds of having syndesmophytes by 67 %. Male AS patients that have more severe US-determined Achilles enthesophyte also associated spinal syndesmophytes suggesting a bone-forming gender-specific phenotype that could be a useful marker predicting of new bone formation.     

Effectiveness of ultrasound treatment applied with exercise therapy on patients with ankylosing spondylitis: a double-blind,randomized, placebo-controlled trial

The aim of our study was to evaluate effectiveness of ultrasound treatment applied with exercise therapy in patients with ankylosing spondylitis. Fifty-two patients, who were diagnosed according to modified New York criteria, were aged 25–60, and have spine pain, were randomly assigned to two groups. Ultrasound (US) and exercise therapy were applied to treatment group (27); placebo US treatment and exercise therapy were applied to control group (25). Patients were evaluated before treatment, at the end of treatment, and 4 weeks after the treatment. Daily and night pain, morning stiffness, patient global assessment (PGA), doctor global assessment (DGA), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire, Ankylosing Spondylitis Disease Activity Score (ASDAS) erythrocyte sedimentation rate (ESR), and ASDAS C-reactive protein (CRP) were used as clinical parameters. In US group, all parameters showed significant improvements at 2 and 6 weeks, in comparison with the baseline. In placebo US group, significant improvement was obtained for all parameters (except tragus-to-wall distance and modified Schober test at 2 weeks and lumbar side flexion and modified Schober test at 6 weeks). Comparison of the groups showed significantly superior results of US group for parameters of BASMI (p < 0.05), tragus–wall distance (p < 0.05), PGA (p < 0.01), and DGA (p < 0.05) at 2 weeks as well as for the parameters of daily pain (p < 0.01), PGA (p < 0.05), DGA (p < 0.01), BASDAI (p < 0.05), ASDAS-CRP (p < 0.05), ASDAS-ESR (p < 0.01), lumbar side flexion (p < 0.01), the modified Schober test (p < 0.01), and ASQoL (p < 0.05) at 6 weeks. Our study showed that ultrasound treatment increases the effect of exercise in patients with ankylosing spondylitis.     

Correlates of disease-specific knowledge among patients with chronic hepatitis B or hepatitis C infection in India

Background

Patient knowledge about chronic diseases increases health-promoting behaviors and improves clinical outcomes. We assessed this association for patients with chronic viral hepatitis.

Methods

Untreated patients chronically infected with HBV (n = 500) or HCV (n = 500) were enrolled at 19 centers across India. A survey, adapted from the US CDC National Health and Nutrition Examination Survey (NHANES) questionnaire, was administered at a single visit to assess HBV/HCV knowledge, community disease awareness, treatment quality, and healthcare barriers. We developed the India Hepatitis Knowledge Index (IHKI), where a higher IHKI score (range 0–10) indicates increased hepatitis knowledge. Multivariate regression models evaluated demographic and disease factors.

Results

The overall mean IHKI score was 5.6 out of 10, with higher scores among patients with HBV (5.9) than HCV (5.3); p < 0.001. In HBV patients lower IHKI was associated with shorter disease duration, government clinic attendance (p < 0.0001), fewer personal experiences with HBV (p < 0.0001), and residing in northern India. Among HCV patients, lower IHKI was associated with shorter disease duration, community (p < 0.0001) and government clinic attendance (p < 0.0001), and fewer personal experiences with HCV (p < 0.0001). Among HBV patients, IHKI was independently associated with disease severity as assessed by MELD score, albumin, and APRI. This association was strongest for HBV patients with elevated ALT and HBV DNA >2000 IU/ml. Among HCV patients, IHKI results had no significant associations with disease severity.

Conclusions

The association of IHKI with disease underscores the need to understand connections between hepatitis knowledge and progression and may guide efforts to address patient education and awareness of chronic viral hepatitis in India.

     

Autoantibodies against myelin sheath and S100β are associated with cognitive dysfunction in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) has been associated with cognitive impairment and peripheral production of autoantibodies. Autoantibodies against central nervous system (CNS) proteins and S100 calcium-binding β (S100β) were found increased in diseases characterized by cognitive impairment like Alzheimer disease and Neuropsychiatric Systemic Lupus Erythematosus (NPSLE). The aim of this study was to investigate the plasma levels of autoantibodies against myelin basic protein (anti-MBP), myelin oligodendrocyte glycoprotein (anti-MOG) and S100β, and their relationships with cognitive performance in RA patients. Twenty patients with active rheumatoid arthritis and 19 age-, sex-, and schooling-matched healthy controls were recruited. Multiple dimensions of cognitive function were evaluated by structured clinical questionnaires. Autoantibodies and S100β levels were assessed by ELISAs. Patients had significantly higher levels of anti-MBP IgG (17.51 ± 1.36 vs. 5.24 ± 0.53 ng/mL), anti-MOG IgG (5.68 ± 1.34 vs. 0.51 ± 0.49 ng/mL), and S100β protein (2.24 ± 0.50 vs. 0.47 ± 0.06) than controls (all p < 0.0001). After adjusting for potential confounders, RA group presented worse cognitive performance involving the working memory and executive functions such as inhibition, flexibility, and mental control in parallel to higher autoantibodies and S100β levels than healthy controls (all p < 0.001). Levels of anti-MBP were negatively associated with delayed verbal recall (DVR; r = ?0.42, p = 0.005), Stroop Color-Word (r = ?0.48, p = 0.004), and N-Back Total scores (r = ?0.59, p < 0.0001) and positively with Trail Making Test B (TMB, r = 0.53, p = 0.001). Negative correlation was found between levels of anti-MOG and DVR (r = ?0.64, p < 0.0001), N-Back Total scores (r = ?0.35, p = 0.03), Stroop Color-Word (r = ?0.51, p = 0.001), and positively with TMB (r = 0.50, p = 0.003). S100β levels were associated with DVR (r = ?0.51, p = 0.002), TMB (r = 0.46, p = 0.008), Stroop Color-Word (r = ?0.67, p < 0.0001), and N-Back Total (r = ?0.52, p = 0.003). RA is associated with impaired cognitive performance associated with higher levels of CNS-related autoantibodies and S100β levels. Given the importance of myelin integrity to cognition, our data indicate that these autoantibodies may be harmful to proper cognitive function.     

Ankylosing spondylitis diagnosis in US patients with back pain: identifying providers involved and factors associated with rheumatology referral delay

This study aimed to identify providers involved in diagnosing ankylosing spondylitis (AS) following back pain diagnosis in the USA and to identify factors leading to the delay in rheumatology referrals. The Truven Health MarketScan® US Commercial Database was searched for patients aged 18–64 years with back pain diagnosis in a non-rheumatology setting followed by AS diagnosis in any setting during January 2000–December 2012. Patients with a rheumatologist visit on or before AS diagnosis were considered referred. Cox regression was used to determine factors associated with referral time after adjusting for age, sex, comorbidities, physician specialty, drug therapy, and imaging procedures. Of 3336 patients included, 1244 (37 %) were referred to and diagnosed by rheumatologists; the others were diagnosed in primary care (25.7 %), chiropractic/physical therapy (7 %), orthopedic surgery (3.8 %), pain clinic (3.6 %), acute care (3.4 %), and other (19.2 %) settings. Median time from back pain diagnosis to rheumatology referral was 307 days and from first rheumatologist visit to AS diagnosis was 28 days. Referred patients were more likely to be younger (hazard ratio [HR]?=?0.986; p?<?0.0001), male (HR?=?1.15; p?=?0.0163), diagnosed with uveitis (HR?=?1.49; p?=?0.0050), referred by primary care physicians (HR?=?1.96; p?<?0.0001), prescribed non-steroidal anti-inflammatory drugs (HR?=?1.55; p?<?0.0001), disease-modifying antirheumatic drugs (HR?=?1.33; p?<?0.0001), and tumor necrosis factor inhibitors (HR?=?1.40; p?=?0.0036), and to have had spinal/pelvic X-ray prior to referral (HR?=?1.28; p?=?0.0003). During 2000–2012, most patients with AS were diagnosed outside of rheumatology practices. The delay before referral to rheumatology was 10 months; AS diagnosis generally followed within a month. Earlier referral of patients with AS signs and symptoms may lead to more timely diagnosis and appropriate treatment.     

Relationship between HRV measurements and demographic and clinical variables in a population of patients with atrial fibrillation

Little is known about the role of HRV in atrial fibrillation (AF) patients. Aim of our study was to assess the relationship between HRV measurements and demographic and clinical variables in a population of 274 AF patients. We selected all consecutive patients with persistent/permanent AF among whom had performed a Holter ECG in our Department from April 2010 to April 2015. Time-domain analysis of HRV was evaluated. Demographic and clinical variables were collected for each patient. At multivariable logistic regression, a higher pNN50 was associated with ACE inhibitors/ARBs (p = 0.016) and a lower pNN50 with obesity (p = 0.037) and higher heart rate (HR) (p < 0.0005). A higher RMSSD was associated with ACE inhibitors/ARBs (p = 0.001), digitalis (p < 0.0005) and beta-blockers (p = 0.002) and a lower RMSSD with a higher HR (p < 0.0005). A higher SDNN_i was associated with ACE inhibitors/ARBs (p < 0.0005), digitalis (p < 0.0005) and beta-blockers (p = 0.002) and a lower SDNN_i with dysthyroidism (p = 0.048) and higher HR (p < 0.0005). A higher SDANN was associated with non-dihydropyiridine calcium-channel-blockers (p = 0.002) and ACE inhibitors/ARBs (p = 0.002) and a lower SDANN with hypertension (p = 0.034), obesity (p = 0.011), stroke (p = 0.031), pneumonia (p = 0.005) and higher HR (p < 0.0005). A higher SDNN was associated with ACE inhibitors/ARBs (p < 0.0005), digitalis (p < 0.0005) and beta-blockers (p = 0.022) and a lower SDNN with obesity (p = 0.012), pneumonia (p = 0.049) and higher HR (p < 0.0005). Our study showed that, in AF patients, there is a direct relationship between some clinical variables and HRV measurements; as for patients with sinus rhythm, even in AF patients this relationship seemed to reflect the autonomic nervous system activity.     

Altered left ventricular performance in aging physically active mice with an ankle sprain injury

We assessed the impact of differing physical activity levels throughout the lifespan, using a musculoskeletal injury model, on the age-related changes in left ventricular (LV) parameters in active mice. Forty male mice (CBA/J) were randomly placed into one of three running wheel groups (transected CFL group, transected ATFL/CFL group, SHAM group) or a SHAM Sedentary group (SHAMSED). Before surgery and every 6 weeks after surgery, LV parameters were measured under 2.5 % isoflurane inhalation. Group effects for daily distance run was significantly greater for the SHAM and lesser for the ATLF/CFL mice (p = 0.013) with distance run decreasing with age for all mice (p < 0.0001). Beginning at 6 months of age, interaction (group × age) was noted with LV posterior wall thickness-to-radius ratios (h/r) where h/r increased with age in the ATFL/CFL and SHAMSED mice while the SHAM and CFL mice exhibited decreased h/r with age (p = 0.0002). Passive filling velocity (E wave) was significantly greater in the SHAM mice and lowest for the ATFL/CFL and SHAMSED mice (p < 0.0001) beginning at 9 months of age. Active filling velocity (A wave) was not different between groups (p = 0.10). Passive-to-active filling velocity ratio (E/A ratio) was different between groups (p < 0.0001), with higher ratios for the SHAM mice and lower ratios for the ATFL/CFL and SHAMSED mice in response to physical activity beginning at 9 months of age. Passive-to-active filling velocity ratio decreased with age (p < 0.0001). Regular physical activity throughout the lifespan improved LV structure, passive filling velocity, and E/A ratio by 6 to 9 months of age and attenuated any negative alterations throughout the second half of life. The diastolic filling differences were found to be significantly related to the amount of activity performed by 9 months and at the end of the lifespan.     

Cartilage collagen type II seromarker patterns in axial spondyloarthritis and psoriatic arthritis: associations with disease activity,smoking and HLA-B27

The aim of the study was to assess the possible association between type II collagen turnover seromarkers and disease profile in patients with axial spondyloarthritis (SpA) and psoriatic arthritis (PsA). Outpatients with axial SpA (n = 110) or PsA (n = 101) underwent clinical examination including disease activity measures and HLA-B27 typing. The procollagen IIA N-terminal peptide (PIIANP) and a matrix metalloproteinase-generated type II collagen fragment (C2M) were quantified in serum by ELISA. C2M was higher in SpA than in controls, 0.41 versus 0.36 ng/ml (p = 0.004), while PIIANP did not differ between patients and healthy subjects, 2252 versus 2142 ng/ml (p = 0.13). However, DMARD-naïve SpA patients had higher PIIANP, 2461 ng/ml (p = 0.01) and C2M, 0.44 ng/ml (p = 0.0007) levels than controls, and PIIANP correlated with CRP (ρ = 0.34). C2M was lower in SpA smokers, 0.36 ng/ml versus non-smokers, 0.43 ng/ml (p = 0.02), while PIIANP was higher in HLA-B27 positive, 2312 ng/ml versus negative patients, 2021 ng/ml (p = 0.03). In PsA, PIIANP and C2M did not differ between patients and controls, but PIIANP was elevated in patients not receiving DMARDs, 2726 ng/ml. In PsA, PIIANP and C2M did not differ according to smoking and HLA-B27. Cartilage degradation assessed by C2M is increased in SpA irrespective of treatment but not in PsA. Cartilage synthesis reflected by PIIANP is increased in untreated SpA and PsA. PIIANP correlates with CRP in SpA while not in PsA. In DMARD-naïve SpA but not in PsA, HLA-B27 positivity and smoking are associated with a chondro-proliferative metabolic pattern.     

Left ventricular subclinical dysfunction associated with myocardial deformation changes in obstructive sleep apnea patients estimated by real-time 3D speckle-tracking echocardiography

Background

Previous studies have demonstrated that patients with obstructive sleep apnea (OSA) may develop left ventricular (LV) diastolic dysfunction. We aimed to study whether OSA patients have LV regional systolic dysfunction with myocardial deformation changes, despite a normal LV ejection fraction, using real-time 3D speckle-tracking echocardiography (Rt3D-STE).

Methods

Seventy-eight patients with OSA and no comorbidities were studied. They were divided into the following three groups according to the apnea–hypopnea index (AHI): 5~15/h as group I (mild OSA, 26 cases), 15~30/h as group II (moderate OSA, 29 cases), and ≥30/h as group III (severe OSA, 23 cases). Thirty gender–age-matched normal subjects were included as controls. The parameters of LV diastolic function were acquired with traditional echocardiography. The LV myocardial deformation parameters were obtained, including the longitudinal (LS), circumferential (CS), radial (RS), and area (AS) strains, with Rt3D-STE.

Results

LV global systolic function was normal in all patients, but diastolic function was impaired in groups II and III (E/E′ was 9.6?±?2.8 and 10.4?±?2.5, respectively, p?<?0.0001). The global LS and AS were significantly reduced in groups II and III compared with the controls and group I (LS 15.9?±?1.4 % and 14.8?±?1.5 % vs 18.2?±?1.7 % and 17.8?±?1.5 %; AS 27.4?±?1.8 % and 24.9?±?2.3 % vs 33.4?±?2.2 % and 32.7?±?2.9 %, respectively, p?<?0.0001), but the global CS and RS were significantly reduced only in group III (17.3?±?1.4 % and 43.1?±?6.5 % vs 19.6?±?1.6 % and 55.4?±?4.0 %, respectively, <0.0001). The severity of OSA was significantly associated with the LV global AS value (r?=??0.80, p?<?0.0001), LS (r?=??0.64, p?<?0.0001), CS (r?=??0.51, p?<?0.0001), and RS (r?=??0.62, p?<?0.0001).

Conclusions

Patients with moderate and severe OSA tended to have both LV diastolic dysfunction and abnormalities in regional systolic function with myocardial deformation changes, in spite of the normal LV ejection fraction. Myocardial strains of the LV were negatively correlated with the AHI. Rt-3DST had important clinical significance in the early evaluation of cardiac dysfunction in OSA patients.

     

Non-driver mutations in patients with <Emphasis Type="Italic">JAK2</Emphasis>V617F-mutated polycythemia vera or essential thrombocythemia with long-term molecular follow-up

JAK2V617F monitoring and NGS of non-driver genes was performed in 100 patients with polycythemia vera (PV) or essential thrombocythemia (ET) with long molecular follow-up. Patients who did not progress to myelofibrosis (MF) or acute myeloid leukemia (AML) after more than 10 years (n?=?50) showed a low frequency of mutations at first sample (18%) and an incidence rate of 1.7 new mutations?×?100 person-years. Mutations were detected at first sample in 83% of PV/ET patients who later progressed to AML (n?=?12) with these patients having a rate of 25.6 mutations?×?100 person-years. Presence of mutations at diagnosis was the unique risk factor for acquiring a new genetic event (HR 2.7, 95% CI 1.1–6.8, p?=?0.03) after correction for age, PV diagnosis, and total duration of hydroxyurea (HU) exposure. Patients with additional mutation at first sample showed a higher probability of developing cytopenia under HU therapy and a higher risk of AML (HR 12.2, 95% CI 2.6–57.1, p?=?0.001) with mutations in ASXL1 (p?<?0.0001), TP53 (p?=?0.01), SRSF2 (p?<?0.0001), IDH1/2 (p?<?0.0001), and RUNX1 (p?<?0.0001) being associated with a higher probability of AML. Myelofibrotic transformation was more frequent in patients with additional mutations, especially in SF3B1 (p?=?0.02) and IDH1/2 (p?<?0.0001) although a persistently high or a progressive increase of the JAK2V617F allele burden while receiving cytoreduction was the strongest predictor of MF transformation (HR 10.8, 95% CI 2.4–49.1, p?=?0.002). In conclusion, NGS may be useful to identify a minority of PV and ET patients with high genetic instability and increased risk of AML transformation.     

Gastrointestinal comorbidities in patients with psoriatic arthritis

Comorbidities associated with psoriatic arthritis (PsA) include cardiovascular diseases, diabetes mellitus, and obesity. This study evaluated the association between PsA and common gastrointestinal (GI) diseases. A retrospective study was performed in Israel’s largest health care provider database between 2002 and 2013. 3161 PsA patients were matched for age and sex with 31610 randomly selected patients. We searched these patients’ records for the presence of peptic ulcer disease (PUD), reflux esophagitis, Crohn’s disease, ulcerative colitis, irritable bowel syndrome (IBS) and celiac disease. T-test was used to compare continuous variables and a Chi-square test was used for categorical variables. Multivariate logistic regression models were used to assess the association between PsA and GI comorbidities. PsA was associated with Crohn’s disease (OR 2.4, 95 %CI: 1.75–3.32, p < 0.0001), ulcerative colitis (OR 2.1, 95 %CI: 1.33–3.26, p = 0.001), reflux esophagitis (OR 1.6, 95 %CI: 1.44–1.78, p < 0.0001), PUD (OR 1.5, 95 %CI: 1.31–1.63, p < 0.0001) and IBS (OR 1.4, 95 %CI: 1.01–1.86, p = 0.045). After controlling for known risk factors, the association remained significant between PsA and Crohn’s disease (OR 2.2, 95 %CI: 1.59–3.03, p < 0.0001), ulcerative colitis (OR 1.9, 95 %CI: 1.21–3.00, p = 0.005), reflux esophagitis (OR 1.5, 95 %CI: 1.31–1.63, p < 0.0001), and PUD (OR 1.3, 95 %CI: 1.12–1.47, p < 0.0001). No significant association was found between PsA and celiac disease. In the current study PsA was associated with gastrointestinal morbidities including Crohn’s disease, ulcerative colitis, PUD and IBS. Physicians treating patients with PsA should be aware of these associations.     

Serum substance P: an indicator of disease activity and subclinical inflammation in rheumatoid arthritis

The aim of the is study is to examine the role of serum substance P (SP) levels as a simple biomarker for rheumatoid arthritis (RA) disease activity, its correlation with other markers of disease activity, and with selected clinical parameters. The study comprised 90 RA patients and 24 healthy controls. RA activity was assessed by means of the disease activity 28-C-reactive protein (DAS28-CRP) index and ultrasound power Doppler (USPD) by the German ultrasound score based on seven joints. SP serum values were obtained by means of an ELISA commercial kit. Statistics were achieved by the Student’s t test and Spearman correlation analysis with Bonferroni correction. As a group, RA patients had significantly increased levels of SP compared with healthy controls (p?<?0.0001). SP levels correlated with DAS28-CRP (r =?0.5050, p?<?0.0001), number of tender joints (NTJ, r =?0.4668, p?<?0.0001), number of swollen joints (NSJ, r?=?0.4439, p?<?0.0001), visual analogue scale (VAS, r?=?0.5131, p?<?0.0001). However, SP did not correlate with CRP levels (r?=?0.0468, p?=?0.6613), nor with the USPD (r?=?0.1740, p?=?0.1009). Elevated serum SP is a common feature of RA patients, which also appears to correlate with clinical measurements of disease activity and with subjective clinical data (NTJ and VAS). Thus, although SP is higher in RA patients with high disease activity, it also detects subtle RA disease activity even in patients in apparent remission, which suggests its usefulness for therapeutic decisions.     

Fibrinolysis in patients with a mild-to-moderate bleeding tendency of unknown cause

In more than 50% of patients with a mild-to-moderate bleeding tendency, no underlying cause can be identified (bleeding of unknown cause, BUC). Data on parameters of fibrinolysis in BUC are scarce in the literature and reveal discrepant results. It was the aim of this study to investigate increased fibrinolysis as a possible mechanism of BUC. We included 270 patients (227 females, median age 44 years, 25–75^th percentile 32–58) with BUC and 98 healthy controls (65 females, median age 47 years, 25–75^thpercentile 39–55). Tissue plasminogen activator (tPA-) antigen and activity, plasminogen activator inhibitor type-1 (PAI-1), tPA-PAI-1 complexes, thrombin activatable fibrinolysis inhibitor (TAFI), α2-antiplasmin, and D-dimer were determined. While PAI-1 deficiency was equally frequent in patients with BUC and controls (91/270, 34%, and 33/98, 34%, p = 0.996), tPA activity levels were more often above the detection limit in patients than in controls (103/213, 48%, and 23/98, 23%, p < 0.0001). We found lower levels of tPA-PAI-1 complexes (6.86 (3.99–10.00) and 9.11 (7.17–13.12), p < 0.001) and higher activity of TAFI (18.61 (15.80–22.58) and 17.03 (14.02–20.02), p < 0.001) and α2-antiplasmin (102 (94–109) and 98 (90–106], p = 0.003) in patients compared to controls. Detectable tPA activity (OR 3.02, 95%CI 1.75–5.23, p < 0.0001), higher levels of TAFI (OR 2.57, 95%CI 1.48–4.46, p = 0.0008) and α2-antiplasmin (OR 1.03, 95%CI 1.01–1.05, p = 0.011), and lower levels of tPA-PAI-1 complexes (OR 0.90, 95%CI 0.86–0.95, p < 0.0001) were independently associated with BUC in sex-adjusted logistic regression analyses. We conclude that the fibrinolytic system can play an etiological role for bleeding in patients with BUC.     

Acute kidney injury following implementation of an enhanced recovery after surgery (ERAS) protocol in colorectal surgery

Purpose

Fluid management within Enhanced Recovery After Surgery (ERAS) protocols is designed to maintain a euvolemic state avoiding the negative sequelae of hypervolemia or hypovolemia. We sought to determine the effect of a recent ERAS protocol implementation on kidney function and on the incidence of postoperative acute kidney injury (AKI).

Methods

A total of 132 elective colorectal resections performed using our ERAS protocol were compared to a propensity-matched group prior to ERAS implementation. Fluid balance, urine output, creatinine, and blood urea nitrogen (BUN) were recorded for all patients, and the incidence of AKI was determined according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria.

Results

Implementation of our ERAS protocol decreased average postoperative length of hospital stay (5.5 vs 7.7 days, p <?0.0001) and time to return of bowel function (2.5 vs 4.1 days, p <?0.0001). The rate of postoperative AKI increased following implementation of the protocol (11.4 vs 2.3%, p <?0.0001). However, by the time of discharge, the average creatinine of ERAS patients who had experienced AKI had returned to their preoperative baseline values (p =?0.9037). Significant univariate predictors of AKI in ERAS patients were longer operative times (p <?0.01) and the diagnosis of diverticulitis (p <?0.01). Within our ERAS patients, AKI was associated with a prolonged postoperative length of hospital stay (p <?0.01).

Conclusions

Despite the proven benefits of the Enhanced Recovery After Surgery (ERAS) protocols, care should be taken during protocol implementation to monitor for and to prevent acute kidney injury.

     

Effects of <Emphasis Type="Italic">S</Emphasis>-Nitrosoglutathione on Electrophysiological Manifestations of Mechanoelectric Feedback

Electromechanical coupling studies have described the intervention of nitric oxide and S-nitrosylation processes in Ca²⁺ release induced by stretch, with heterogeneous findings. On the other hand, ion channel function activated by stretch is influenced by nitric oxide, and concentration-dependent biphasic effects upon several cellular functions have been described. The present study uses isolated and perfused rabbit hearts to investigate the changes in mechanoelectric feedback produced by two different concentrations of the nitric oxide carrier S-nitrosoglutathione. Epicardial multielectrodes were used to record myocardial activation at baseline and during and after left ventricular free wall stretch using an intraventricular device. Three experimental series were studied: (a) control (n?=?10); (b) S-nitrosoglutathione 10 µM (n?=?11); and (c) S-nitrosoglutathione 50 µM (n?=?11). The changes in ventricular fibrillation (VF) pattern induced by stretch were analyzed and compared. S-nitrosoglutathione 10 µM did not modify VF at baseline, but attenuated acceleration of the arrhythmia (15.6?±?1.7 vs. 21.3?±?3.8 Hz; p?<?0.0001) and reduction of percentile 5 of the activation intervals (42?±?3 vs. 38?±?4 ms; p?<?0.05) induced by stretch. In contrast, at baseline using the 50 µM concentration, percentile 5 was shortened (38?±?6 vs. 52?±?10 ms; p?<?0.005) and the complexity index increased (1.77?±?0.18 vs. 1.27?±?0.13; p?<?0.0001). The greatest complexity indices (1.84?±?0.17; p?<?0.05) were obtained during stretch in this series. S-nitrosoglutathione 10 µM attenuates the effects of mechanoelectric feedback, while at a concentration of 50 µM the drug alters the baseline VF pattern and accentuates the increase in complexity of the arrhythmia induced by myocardial stretch.     

Association between gait characteristics and endothelial oxidative stress and inflammation in patients with symptomatic peripheral artery disease

The aim of the study was to determine whether gait characteristics were associated with endothelial cell inflammation, oxidative stress, and apoptosis and with circulating biomarkers of inflammation and antioxidant capacity in older patients with symptomatic peripheral artery disease (PAD). Gait measurements of 231 symptomatic men and women with PAD were assessed during a 4-m walk test. Patients were further characterized on endothelial effects of circulating factors present in the sera using a cell culture-based bioassay on primary human arterial endothelial cells and on circulating inflammatory and vascular biomarkers. In a multivariate regression model for gait speed, the significant independent variables were age (p < 0.001), intercellular cell adhesion molecule-1 (ICAM-1) (p < 0.001), diabetes (p = 0.003), sex (p = 0.003), and history of cerebrovascular accidents (p = 0.021). In multivariate analyses for gait cadence, the significant independent predictors included high-sensitivity C-reactive protein (HsCRP) (p < 0.001), diabetes (p = 0.001), and hypertension (p = 0.001). In a multivariate regression model for gait stride length, the significant independent variables were HsCRP (p < 0.001), age (p < 0.001), ICAM-1 (p < 0.001), hypertension (p = 0.002), cellular reactive oxygen species production (p = 0.007), and sex (p = 0.008). Higher levels of circulating biomarkers of inflammation and endothelial cell oxidative stress were associated with slower gait speed, slower cadence, and shorter stride length in older symptomatic patients with PAD. Additionally, this profile of impaired gait was more evident in older patients, in women, and in those with diabetes, hypertension, and history of cerebrovascular accidents.     

Effect of physical activity on heart rate variability and carotid intima-media thickness in older people

We investigated the effect of physical activity on heart rate variability (HRV) and carotid intima-media thickness (IMT) in elderly subjects and the relationship between HRV and IMT. Thirty-two elderly sedentary subjects and 32 age-matched endurance athletes underwent ultrasonography of the carotid wall for measuring IMT, and 24-h ECG monitoring for measuring HRV. Elderly athletes had evidence of increased vagal activity in the time (SDANN, rMSSD, and pNN50; p < 0.01) and frequency domain (HF and LF/HF ratio, p < 0.01) with respect to sedentary subjects. Moreover, athletes showed lower IMT than control subjects (p < 0.01). In the whole population SDNN was inversely related to IMT, respectively (r = ?0.60 and r = ?0.58, p < 0.0001), while LF/HF ratio related positively to IMT. In conclusion, this study demonstrated that in aging HRV is negatively associated with IMT, a putative index of atherosclerosis, confirming cardiac autonomic neuropathy as part of the pathophysiological pathway for atherosclerosis. It confirms that the regular physical activity represents a valuable strategy to counter age-related impairments of cardiac autonomic activity and artery structural changes.     

A retrospective analysis of the impact of telephonic counseling on dietary and lifestyle modifications in Indian patients with type 2 diabetes mellitus

Dietary and lifestyle modifications are critical in the management of type 2 diabetes mellitus (T2DM). However, in a resource-constrained setting, providing physical counseling for dietary and lifestyle modifications is a challenge. Therefore, SPARSH, a call center based, telephonic counseling program was set up for patients with T2DM. In this study, effect of SPARSH services on dietary and lifestyle parameters of patients with T2DM was analyzed. Adult patients who received counseling regularly for at least 14 months were selected. At the end of 14 months, change from baseline in various dietary and lifestyle parameters was evaluated using t test and McNemar’s test at 5% significance level. Overall, 1283 patients were included. At the end of 14 months, change in dietary parameters was as follows: total calories, carbohydrates, and fat consumption decreased significantly by 169.1 kcal/day, 16.2 g/day, and 3.1 g/day, respectively (p?<?0.0001); proteins intake increased by 1.0 g/day (p?=?0.0043); cereals, alcohol, and junk food consumption decreased by 1.1 exchanges/day, 34.9 kcal/day, and 46.0 kcal/day, respectively (p?<?0.0001); fruits and vegetable consumption increased by 0.2 and 0.4 exchanges/day, respectively (p?<?0.0001); dietary fiber intake increased by 0.9 g/day (p?=?0.0207). Change in lifestyle parameters was as follows: increase in frequency and duration of exercise by 1.2 days/week and 1.3 h/week, respectively; self-inspection of feet and footwear by 1.5 and 1.0 times/week, respectively; and decrease in smoking by 2 cigarettes/day (p?<?0.0001). Regular telephonic counseling significantly improved dietary and lifestyle parameters in T2DM patients.     

Risk for latent and active tuberculosis in Germany

Purpose

Few individuals that are latently infected with M. tuberculosis latent tuberculosis infection(LTBI) progress to active disease. We investigated risk factors for LTBI and active pulmonary tuberculosis (PTB) in Germany.

Methods

Healthy household contacts (HHCs), health care workers (HCWs) exposed to M. tuberculosis and PTB patients were recruited at 18 German centres. Interferon-γ release assay (IGRA) testing was performed. LTBI risk factors were evaluated by comparing IGRA-positive with IGRA-negative contacts. Risk factors for tuberculosis were evaluated by comparing PTB patients with HHCs.

Results

From 2008–2014, 603 HHCs, 295 HCWs and 856 PTBs were recruited. LTBI was found in 34.5% of HHCs and in 38.9% of HCWs. In HCWs, care for coughing patients (p = 0.02) and longstanding nursing occupation (p = 0.04) were associated with LTBI. In HHCs, predictors for LTBI were a diseased partner (odds ratio 4.39), sexual contact to a diseased partner and substance dependency (all p < 0.001). PTB was associated with male sex, low body weight (p < 0.0001), alcoholism (15.0 vs 5.9%; p < 0.0001), glucocorticoid therapy (7.2 vs 2.0%; p = 0.004) and diabetes (7.8 vs. 4.0%; p = 0.04). No contact developed active tuberculosis within 2 years follow-up.

Conclusions

Positive IGRA responses are frequent among exposed HHCs and HCWs in Germany and are poor predictors for the development of active tuberculosis.

     

Ultrasound-detected joint inflammation and B cell count: related variables for rituximab-treated RA patients?

This cross-sectional observational study aimed to explore the relationship between B cell count and ultrasound (US)-detected synovitis, in patients with rheumatoid arthritis treated with rituximab. Thirty-seven consecutive RA patients treated with RTX were recruited for the study. The patients underwent clinical [i.e., Disease Activity Score 28 joints (DAS28)], laboratory, and US assessment of 12 joints. Each joint was semiquantitatively (0–3) scored on B-mode and power Doppler mode. The scores were summed, and a global index was created for BM (BMS) and PD scores (PDI) synovitis. BM subclinical synovitis was evident in all patients, with PD synovial signal detected in 16 patients (43.2 %). No correlation was found between DAS28 and US scores. B cells were detected in 27 (72.9 %) patients, but there was no association in the mean B cell count and disease activity as measured by DAS28 (DAS28 < 2.6 = 34.53, DAS28 > 2.6 = 49.45, p = 0.52) and PDI score (PDI < 1 = 49.48, PDI > 1 = 35.44, p = 0.54). There was no correlation between the B cell count and DAS28, BMS, and PDI (r = 0.020, p = 0.907; r = ?0.151, p = 0.371; r = ?0.099, p = 0.558, respectively). In RTX-treated RA patients, no relationship could be established between US-detected synovitis and peripheral blood B cell count.