Improvement in Olfaction in Patients With CRSwNP and Severe Asthma Taking Anti-IgE and Anti-IL-5 Biologics: A Real-Life Study.

BACKGROUND AND OBJECTIVES: Chronic rhinosinusitis with nasal polyps (CRSwNP), which is characterized by partial loss of smell (hyposmia) or total loss of smell (anosmia), is commonly associated with asthma and/or nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD). CRSwNP worsens disease severity and quality of life. The objective of this real-world study was to determine whether biological treatments prescribed for severe asthma can improve olfaction in patients with CRSwNP. A further objective was to compare the improvement in in olfaction in N-ERD and non-N-ERD subgroups. METHODS: We performed a multicenter, noninterventional, retrospective, observational study of 206 patients with severe asthma and CRSwNP undergoing biological treatment (omalizumab, mepolizumab, benralizumab, or reslizumab). RESULTS: Olfaction improved after treatment with all 4 monoclonal antibodies (omalizumab [35.8%], mepolizumab [35.4%], reslizumab [35.7%], and benralizumab [39.1%]), with no differences between the groups. Olfaction was more likely to improve in patients with atopy, more frequent use of short-course systemic corticosteroids, and larger polyp size. The proportion of patients whose olfaction improved was similar between the N-ERD (37%) and non-N-ERD (35.7%) groups. CONCLUSIONS: This is the first real-world study to compare improvement in olfaction among patients undergoing long-term treatment with omalizumab, mepolizumab, reslizumab, or benralizumab for severe asthma and associated CRSwNP. Approximately 4 out of 10 patients reported a subjective improvement in olfaction (with nonsignificant differences between biologic drugs). No differences were found for improved olfaction between the N-ERD and non-N-ERD groups.

Serum microRNAs Catalog Asthma Patients by Phenotype.

BACKGROUND AND OBJECTIVES: Asthma is a chronic inflammatory condition of the airways with a complex pathophysiology. Stratification of asthma subtypes into phenotypes and endotypes should move the field forward, making treatment more effective and personalized. Eosinophils are the key inflammatory cells involved in severe eosinophilic asthma. Given the health threat posed by eosinophilic asthma, there is a need for reliable biomarkers to identify affected patients and treat them properly with novel biologics. microRNAs (miRNAs) are a promising diagnostic tool. The aim of this study was to identify serum miRNAs that can phenotype asthma patients. METHODS: Serum miRNAs of patients with eosinophilic asthma (N=40) and patients with noneosinophilic asthma (N=36) were evaluated using next-generation sequencing, specifically miRNAs-seq, and selected miRNAs were validated using RT-qPCR. Pathway enrichment analysis of deregulated miRNAs was performed. RESULTS: Next-generation sequencing revealed 15 miRNAs that were expressed differentially between eosinophilic and noneosinophilic asthma patients, although no differences were observed in the miRNome between atopic and nonatopic asthma patients. Of the 15 miRNAs expressed differentially between eosinophilic and noneosinophilic asthma patients, hsa-miR-26a-1-3p and hsa-miR-376a-3p were validated by RT-qPCR. Expression levels of these 2 miRNAs were higher in eosinophilic than in noneosinophilic asthma patients. Furthermore, expression values of hsa-miR-26a-1-3p correlated inversely with peripheral blood eosinophil count, and hsa-miR-376a-3p expression values correlated with FeNO values and the number of exacerbations. Additionally, in silico pathway enrichment analysis revealed that these 2 miRNAs regulate signaling pathways associated with the pathogenesis of asthma. CONCLUSIONS: hsa-miR-26a-1-3p and hsa-miR-376a-3p could be used to differentiate between eosinophilic and noneosinophilic asthma.

Increasing Incidence of Pediatric Eosinophilic Esophagitis in the Southwest of Madrid, Spain.

OBJECTIVES: The incidence of eosinophilic esophagitis is unknown in our area. The aim of our study was to determine the incidence of eosinophilic esophagitis and its possible association with the most frequent absolute annual pollen counts. METHODS: A descriptive retrospective multicenter observational study was designed to calculate the incidence of eosinophilic esophagitis in children aged under 15 years in the southwest region of Madrid, Spain in 2002-2013 (data were provided by the Statistics Institute of Madrid). We collected data on age, sex, clinical presentation, and date of endoscopic diagnosis. Relative risk (RR) was estimated (Stata v.11) using negative binomial regression models to assess the association between incidence and pollen counts (provided by Subiza Clinic). RESULTS: The study population comprised 254 patients (192 male [75.6%], aged 0.5-14.99 years). The clinical presentation was esophageal impaction in 23.6%, dysphagia in 22%, gastroesophageal reflux-like symptoms in 44.9%, and other findings in 9.4%. The annual incidence from 2002 to 2013 per 100 000 children aged <15 years per year was, respectively, 0.81, 1.5, 0.37, 3.17, 3.07, 4.36, 6.87, 7.19, 8.38, 9.05, 9.14, and 9.68. The incidence of eosinophilic esophagitis increased by an average of 19% annually (RR, 1.19; 95%CI, 1.14-1.25; P<.001). In the overall analysis, the relationship between incidence and absolute annual and monthly counts during the pollen seasons of the respective pollen types was analyzed only for Platanus species, which had an RR >1 (1.17 and 1.06, respectively) (P<.05). CONCLUSION: The incidence of diagnosis of pediatric eosinophilic esophagitis increased by an average of 19% annually. No significant association was found between incidence and pollen counts, except for a weak association with Platanus species.

Impact of Chiropractic Manipulation on Bone and Skeletal Muscle of Ovariectomized Rats.

Evidence suggests that chiropractic manipulation might exert positive effects in osteoporotic patients. The aim of this study was to evaluate the effects of chiropractic manipulation on bone structure and skeletal muscle in rats with bone loss caused by ovariectomy (OVX). The 6-month old Sprague-Dawley rats at 10 weeks following OVX or sham operation (Sh) did not suffer chiropractic manipulation (NM group) or were submitted to true chiropractic manipulation using the chiropractic adjusting instrument Activator V® three times/week for 6 weeks as follows: Force 1 setting was applied onto the tibial tubercle of the rat right hind limb (TM group), whereas the corresponding left hind limb received a false manipulation (FM group) consisting of ActivatorV® firing in the air and slightly touching the tibial tubercle. Bone mineral density (BMD) and bone mineral content (BMC) were determined in long bones and L3-L4 vertebrae in all rats. Femora and tibia were analyzed by µCT. Mechano growth factor (MGF) was detected in long bones and soleus, quadriceps and tibial muscles by immunohistochemistry and Western blot. The decrease of BMD and BMC as well as trabecular bone impairment in the long bones of OVX rats vs Sh controls was partially reversed in the TM group versus FM or NM rats. This bone improvement by chiropractic manipulation was associated with an increased MGF expression in the quadriceps and the anterior tibial muscle in OVX rats. These findings support the notion that chiropractic manipulation can ameliorate osteoporotic bone at least partly by targeting skeletal muscle.

Suicide ideation among oncologic patients in a Spanish ward.

Oncologic patients are exposed to a higher risk of suicidal behaviors than the general population. In this study, we aim to examine the severity of suicidal ideation in a sample of oncologic patients considering different psychological and clinical features. We interviewed 202 inpatients receiving curative or palliative treatment in a medical oncology ward of a Spanish hospital during the period 2012-2014. A complete assessment of psychosocial factors, cancer diagnoses (lung, colon rectum, and genitourinary system), and suicidal behaviors were made during admission, including validated questionnaires about depression, anxiety, personality, quality of life, body image, life threatening events, hopelessness, and suicidal ideation. The characteristics of inpatients with high and low suicidal ideation were retrospectively compared. A logistic regression model was constructed to examine the relationship between the significant factors retained after the univariate analyses. One of every four patients (n = 51; 25.24%) presented high scores of suicidal ideation. Logistic regression analyses retained depression (OR = 3.55; 95% CI = 1.25-11.68; p = .016), hopelessness (OR = 8.78; 95% CI = 3.44-25.88; p ≤ .001), personality (OR = .44; 95% CI = .2-.96; p = .038), and advanced age (OR = 2.60; 95% CI = 1.18-5.98; p = .016) as the main risk factors for high suicidal ideation. Suicidal ideation was frequent among oncologic patients. These patients should receive closer monitoring, especially, when old, retired, or severely depressed.

Manual scoring of periodic limb movements in children: is it still necessary?

OBJECTIVE: Although manual scoring has been classically considered the gold standard to identify periodic leg movements (PLM), it is a very time consuming and expensive process, also subject to variability in interpretation. In the last decades, different authors have observed reasonably good agreement between automated PSG scoring algorithms and manual scoring in adults, according to established criteria. We aim to compare the automatic software analysis of our polysomnogram with the manual staging in children with sleep-disordered breathing. METHODS: We performed a semiautomatic method, in which an experienced technician watched the video recording and removed from the automatic analysis those movements that did not correspond to true candidate leg movement (LM). RESULTS: A total of 131 PSGs were studied; applying the established criteria, 65 children were diagnosed of obstructive sleep apnea, and 66 presented snoring but with no sleep apnea. The mean age was 6.7 years (±1.7) and twenty-five children (19.08 %) had a PLMI >5/h. Statistical differences were found not only for PLMI (manual: 2.20 (0.7, 4.1) vs automatic (6.4 (3.85,9.5); p < 0.001), but for almost of all indexes assessed between the automatic and the manual scoring analysis. The level of concordance was only moderate for PLM index (0.63 [0.51-0.72]); showing that, unlike the articles published in the adult population, automatic analysis is not accurate in children and, manually or semi-automatically analysis as ours need to be done. CONCLUSION: It seems that PLM detection algorithm might work accurately but, the real need would be a true LM detection algorithm.

Assessment of changes in sexual function in patients undergoing endoscopic surgery for upper urinary tract lithiasis.

OBJECTIVE: To evaluate the effect of endoscopic surgery on sexual function in patients with upper urinary tract (UUT) lithiasis. MATERIAL AND METHODS: We conducted an observational, prospective, longitudinal study with a single cohort of cases undergoing ureteroscopy (URS), retrograde intrarenal surgery (RIRS), or endoscopic combined intrarenal surgery (ECIRS). Patients' sexual response was assessed with questionnaires in the 30 days prior to surgery, and at one and three months after surgery. The International Index of Erectile Function (IIEF-t) was used in male patients, and the Female Sexual Function Index (FSFI) was used in female patients. RESULTS: Seventy patients - 34 men and 36 women - completed the study. Among men, the IIEF-t did not show significant difference between baseline scores (64.1 ±â€¯7.50) and those obtained at 3 months (63.8 ±â€¯9.51), with a non-significant decrease (p = 0.054) at the first month (61.4 ±â€¯10.4). Subdomains did not worsen at 3 months, and desire (IIEF-SD) improved from 7.3 ±â€¯1.9 to 8.0 ±â€¯1.8. Among women, the FSFI-t did not change significantly after surgery: baseline score (27.3 ±â€¯4.1), 1-month score (26.8 ±â€¯3.7) and 3-month score (27.5 ±â€¯4.2). No subdomain worsened at the third month. CONCLUSION: Endoscopic surgery for UUT is a safe technique in both sexes with no negative effect on sexual function. There are no differences between the baseline IIEF-t and FSFI-t scores and those obtained at 3 months.

Biochemical markers of bone turnover and clinical outcome in patients with renal cell and bladder carcinoma with bone metastases following treatment with zoledronic acid: The TUGAMO study.

BACKGROUND: Levels of bone turnover markers (BTM) might be correlated with outcome in terms of skeletal-related events (SRE), disease progression, and death in patients with bladder cancer (BC) and renal cell carcinoma (RCC) with bone metastases (BM). We try to evaluate this possible correlation in patients who receive treatment with zoledronic acid (ZOL). METHODS: This observational, prospective, and multicenter study analysed BTM and clinical outcome in these patients. Serum levels of bone alkaline phosphatase (BALP), procollagen type I amino-terminal propeptide (PINP), and beta-isomer of carboxy-terminal telopeptide of type I collagen (ß-CTX) were analysed. RESULTS: Patients with RCC who died or progressed had higher baseline ß-CTX levels and those who experienced SRE during follow-up showed high baseline BALP levels. In BC, a poor rate of survival was related with high baseline ß-CTX and BALP levels, and new SRE with increased PINP levels. Cox univariate analysis showed that ß-CTX levels were associated with higher mortality and disease progression in RCC and higher mortality in BC. Bone alkaline phosphatase was associated with increased risk of premature SRE appearance in RCC and death in BC. CONCLUSION: Beta-isomer of carboxy-terminal telopeptide of type I collagen and BALP can be considered a complementary tool for prediction of clinical outcomes in patients with BC and RCC with BM treated with ZOL.

Usefulness of bone turnover markers as predictors of mortality risk, disease progression and skeletal-related events appearance in patients with prostate cancer with bone metastases following treatment with zoledronic acid: TUGAMO study.

BACKGROUND: Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA). METHODS: This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4 mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (ß-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded. RESULTS: Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with ß-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression. CONCLUSION: In patients with PCa and bone metastases treated with ZA, ß-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially important.

Prevalence and European comparison of dementia in a ≥75-year-old composite population in Spain.

OBJECTIVES: To estimate dementia prevalence in Spain. MATERIALS AND METHODS: Nine probabilistic and geographically defined samples participated. A screening design based on the MMSE was implemented. Positively screened individuals underwent clinical evaluation. The total number of cases in Spain was estimated. Prevalence was confronted to that of other European countries. RESULTS: Five hundred and forty-six persons aged ≥75 participated, 49 had dementia (35 with Alzheimer's disease [AD], 10 with vascular dementia [VD], 4 other; 25 first diagnosed in the study). Age- and sex-adjusted prevalence and estimated nationwide cases were 7.5% (95% CI 5.4-9.7), 5.6 (95% CI 3.7-7.5) and 1.4 (95% CI 0.5-2.3), and 290,000 (95% CI 208,000-372,000), 214,000 (95% CI 141,000-288,000) and 54,000 (95% CI 20,000-88,000) for dementia, AD and VD, respectively. CONCLUSIONS: Dementia prevalence in Spain is comparable to other European populations, while a high number of undiagnosed cases live in the community. The potential impact of Mediterranean diet, hypertension control and decreasing vascular risk factors is discussed.

Agreement and differences between macular values in children using two types of spectral optical coherence tomography.

OBJECTIVES: To determine the degree of agreement and differences between macular parameters according to sex, age, laterality, ethnicity and type of optical coherence tomography (OCT) in paediatric patients. MATERIALS AND METHODS: Prospective, transversal, and comparative study. OCT Spectralis and OCT Cirrus were used to obtain the macular values of both eyes in 100 patients between 5 and 15 years without ocular pathology. Due to the similarity between the values of both eyes, in the final sample we only considered the right eyes (OD) (n = 100). RESULTS: The average central macular thickness (CMT) was 244.2 µm with Cirrus and 261.7 µm with Spectralis. The degree of agreement for the GMC was moderate (Intraclass Correlation Coefficient: 0.66) and from low to very low in the other quadrants. The GMC values of both systems were significantly higher in men than in women (P < .05). The macular retinal nerve fibre layer (mRNC), ganglion cell layer (GCC), the inner plexiform layer (IPLC), and the inner nuclear layer (INFL) had significantly higher values in men than in women (P < .01). There were no statistically significant differences in the GMC by age and laterality, however it was significantly higher in ethnic European children than in ethnic Latin American children; Cirrus (P = .042) and Spectralis (P = .033). CONCLUSIONS: Macular parameters obtained by OCT Spectralis and OCT Cirrus should not be interchangeable in pediatric patients.

Incidence of spinal cord injury worldwide: a systematic review.

BACKGROUND: Incidence studies of spinal cord injury (SCI) are important for health-care planning and epidemiological research. This review gives a quantitative update on SCI epidemiology worldwide through a statistical evaluation of incidence rates. METHODS: A systematic review was conducted. For each study, the crude rate ratio was calculated and, when possible, age- and gender-adjusted incidence rate ratios with 95% CI were determined by direct adjustment or using Poisson regression. RESULTS: Thirteen studies were included. Annual crude incidence rates in traumatic SCI varied from 12.1 per million in The Netherlands to 57.8 per million in Portugal. Compared to the Portuguese reference study, incidence rates showed a 3-fold variation, with the highest rates in Canada and Portugal. Most traumatic SCI studies showed a bimodal age distribution. The first peak was found in young adults between 15 and 29 years and a second peak in older adults (mostly > or = 65 years). Motor vehicle accidents and falls were the most prevalent causes of injury accounting for nearly equal percentages. In contrast, another age pattern in non-traumatic SCI reflected steadily increasing incidence with advancing age. CONCLUSIONS: The results show significant variation in SCI incidence with changing epidemiological patterns. A trend towards increased incidence in the elderly was observed, likely due to falls and non-traumatic injury.

Beneficial effects of manually assisted chiropractic adjusting instrument in a rabbit model of osteoarthritis.

Osteoarthritis (OA) is a degenerative disease characterized by injury of all joint tissues. Our previous study showed that in experimental osteoporosis, chiropractic manipulation (CM) exerts protective effects on bone. We here assessed whether CM might ameliorate OA by improving subchondral bone sclerosis, cartilage integrity and synovitis. Male New-Zealand rabbits underwent knee surgery to induce OA by anterior cruciate ligament injury. CM was performed using the chiropractic instrument ActivatorV 3 times/week for 8 weeks as follows: force 2 setting was applied to the tibial tubercle of the rabbit right hind limb (TM-OA), whereas the corresponding left hind limb received a false manipulation (FM-OA) consisting of ActivatorV firing in the air and slightly touching the tibial tubercle. After sacrifice, subchondral bone integrity was assessed in the tibiae by microCT and histology. Cartilage damage and synovitis were estimated by Mankin's and Krenn's scores, respectively, and histological techniques. Bone mineral density and content in both cortical and trabecular compartments of subchondral bone decreased in OA rabbits compared to controls, but partially reversed in the TM-OA group. Trabecular bone parameters in the latter group also showed a significant improvement compared to FM-OA group. Moreover RANKL, OPG, ALP and TRAP protein expression in subchondral bone significantly decreased in TM-OA rabbits with respect to FM-OA group. CM was associated with lower Mankin's and Krenn's scores and macrophage infiltrate together with a decreased protein expression of pro-inflammatory, fibrotic and angiogenic factors, in TM-OA rabbits with respect to FM-OA. Our results suggest that CM may mitigate OA progression by improving subchondral bone as well as cartilage and synovial membrane status.

Agreement in retinal nerve fiber layer values and comparison in children using two optical coherence tomography devices. / Grado de concordancia y diferencias entre los valores de capa de fibras nerviosas de la retina peripapilar en niños mediante dos tipos de tomografía de coherencia óptica espectral.

OBJECTIVE: To assess absolute agreement and differences in peripapillary retinal nerve fiber layer (pRNFL) values according to sex, age, laterality, origin and optical coherence tomography (OCT) type in normal pediatric patients undergoing OCT scans using both Cirrus and Spectralis. MATERIAL AND METHODS: Prospective, cross-sectional, and comparative study. We used Spectralis OCT and Cirrus OCT to measure optic disc values of both eyes in one hundred pediatric patients (age 5 to 15years), with no previous ocular pathology or systemic disease that could affect the eye. Due to the similarity between eyes, only right eyes were considered (n=100). RESULTS: The average peripapillary retinal nerve fiber layer (pRNFL) values were 99.6µm with Cirrus and 106.7µm with the Spectralis system. The four quadrants followed the ISNT rule (inferior-superior-nasal-temporal). The average pRNFL measures correlated negatively with the AL (P<.01) in both OCTs, and the degree of agreement between OCTs for pRNFL and inferior RNFL was moderate (CCI: 0.67 and 0.61, respectively), and low in the rest of the sectors. The average pRNFL values of both OCTs were higher in women than in men (P>.05) and there were also no statistical differences in the pRNFL according to age or laterality (P>.05). All RNFL values were significantly different between both types of OCTs (P<.05) and average pRNFL values were significantly thicker (P<.05) in Latin American than in European children in both eyes. CONCLUSIONS: We suggest that the respective peripapillary RNFL values obtained using these two OCTs should not be considered interchangeable in pediatric patients.

Parathormone Levels Are Independently Associated with the Presence of Left Ventricular Hypertrophy in Patients with Coronary Artery Disease.

BACKGROUND: Abnormalities of mineral metabolism and inflammation may affect the cardiovascular system. We have assessed the relationship of left ventricular hypertrophy (LVH) with inflammation and mineral metabolism. METHODS: LVH was measured in 146 outpatients with stable coronary artery disease (SCAD) using echocardiography. Calcidiol (a vitamin D metabolite), parathyroid hormone (PTH), fibroblast growth factor-23, high-sensitivity C-reactive protein, MCP-1 (monocyte chemoattractant protein-1), galectin-3, NGAL (neutrophil gelatinase-associated lipocalin), and sTWEAK (soluble TNF-related weak inducer of apoptosis) plasma levels were studied. RESULTS: LVH, defined as septal thickness ≥11 mm, was present in 19.9% of cases. These patients were older [75.0 (61.0-81.0) vs 64.0 (51.0-76.0) years; p=0.002], had higher prevalence of left ventricular ejection fraction (LVEF)>40%, and had higher PTH [84.7 (59.6-104.7) vs 63.2 (49.2-85.2) pg/ml; p=0.007], galectin-3 [9.6 (8.0-11.1) vs 8.3 (6.9-9.9) ng/ml; p=0.037], and NGAL (208.5±87.6 vs 173.9±73.4 ng/ml; p=0.031) plasma levels than those without LVH. Glomerular filtration rate was lower in patients with LVH than in those without it (65.1±20.0 vs 74.7±19.9 mL/min/1.73 m2; p=0.021). There were no significant differences in hypertension (79.3 vs 68.4%; p=0.363) or sex between both groups. Variables showing differences based on univariate analysis and hypertension were entered into a logistic regression analysis. Only age [odds ratio (OR) =1.052 (1.011-1.096); p=0.013], PTH plasma levels [OR=1.017 (1.003-1.031); p=0.021], and LVEF>40% [OR=7.595 (1.463-39.429); p=0.016] were independent predictors of LVH. CONCLUSIONS: In patients with SCAD, elevated PTH levels are independently associated with the presence of LVH. Further studies are needed to elucidate the role of PTH in the development of myocardial hypertrophy.