[Correlations between the lumbrical-interosseous latency comparison test and standard tests used in the diagnosis of carpal tunnel syndrome]. / Korelacje testu porównujacego róznice latencji miedzy miesniem glistowatym a miedzykostnym z testami standardowymi stosowanymi w diagnostyce zespolu ciesni nadgarstka.

The diagnosis of patients with severe carpal tunnel syndrome (CTS) who do not respond to median nerve stimulation and of those with early CTS who report symptoms but show no abnormalities in standard tests is the most challenging. The aim of the study was to assess correlations between the 2LI-DML test and standard tests used for the diagnosis of CTS (SL-D2, DML-APB, D4M-D4U). The study involved 172 patients (253 nerves) with clinical symptoms of CTS. The sensitivity of the 2LI-DML test and standard tests was analyzed in 6 groups of patients classified according to the severity of CTS, assessed by an electrophysiological study. We showed a significant relationship between the results of the 2LI-DML test and those of standard tests (SL-D2, DML-APB, D4M-D4U), as revealed by a topographic analysis of sensory and motor fibers of the median nerve at the site most vulnerable to compression.

Scraping nasal cytology in the diagnostics of rhinitis and the comorbidities.

Nasal scraping cytology is a non-invasive tool used in the diagnostics of allergic and non-allergic rhinitis. The study aimed to analyze to what extent the cytological picture of the nasal mucosa coincides with the diagnosis of a given disease, taking into account the content of eosinophils. Retrospective analysis of the cytograms performed in 842 patients was carried out in relation to the disease entities and the content of eosinophils. Significant relationship between the Epith:Infl ratio and the four groups of diseases (Chi2 = 9.6488; p = .014) was confirmed. The more intensive inflammation was found, the higher percentage of patients had manifested the increased level of eosinophils (> 1% in the inflammatory cells). The value of 20% of eosinophils in all counted cells corresponds to around 45% of eosinophils in the inflammatory cells in patients with the evident inflammatory picture. Allergic rhinitis presents a different cytological picture regarding the eosinophilic reaction against the background of the inflammation process: the higher degree of inflammation observed, the lower amount of eosinophils detected, with the exception of allergic rhinitis provoked by pollen allergens.

The Associations of Perceived and Oxidative Stress with Hypertension in a Cohort of Police Officers.

PURPOSE: Associations between perceived stress and oxidative stress marker and metabolic syndrome (MetS) components were investigated in a cohort of police officers. METHODS: Cross-sectional data from a cohort of non-diabetic subjects (n=233; 19F), median [interquartile range] age 50 [37-44] years, were analysed. MetS was construed in line with International Diabetes Federation (IDF) criteria and perceived stress with Cohen's 10-item Perceived Stress Scale. Plasma oxidative stress marker (free 8-iso-prostaglandin F2α; 8-iso-PGF2α), presence of coronary plaque, carotid artery intima-media thickness (cIMT), and physical activity level were also determined. RESULTS: Obesity was established in 100 (42.92%), hypertension in 111 (47.64), whereas MetS was identified in 104 (44.63%) of the study subjects. A significant difference (p=0.003) in plasma 8-iso-PGF2α level, depending on the MetS components status, was noted. The associations of perceived stress with plasma 8-iso-PGF2α level and the select study variables were gender-specific. In multivariate analysis (adjusted for age and current smoking), positive associations of plasma 8-iso-PGF2α levels with PSS score (B=0.108, 95% CI [0.008, 0.209], p=0.03) and systolic blood pressure (B=0.029, 95% CI [0.003, 0.057], p=0.02) in men only were established. Both the perceived stress (OR 1.101, 95% CI [1.001-1.202], p=0.03) and plasma 8-iso-PGF2α levels (OR 1.223, 95% CI [1.046-1.432], p=0.01) impacted the prevalence of hypertension. Out of the MetS components, the effect of waist circumference (OR=1.138, 95% CI [1.064-1.218], p=0.0001) and glucose (B=2.696, 95% CI [1.081-6.725], p=0.03) were also encountered. No such associations were noted in women, though, neither in univariate nor in multivariate analyses. The prevalence of coronary plaque (0.001), obesity (p<0.001), hypertension (p<0.001) and median cIMT value (p=0.005), as well as leisure-time (p=0.04) and total walking physical activity (p=0.03), differed significantly between the subgroups stratified by MetS components status. CONCLUSION: Both the perceived and oxidative stress were found instrumental in promoting hypertension in a cohort of police officers under study, whereas all study outcomes were conclusively gender-related.

Potential roles of psychological and oxidative stress in insulin resistance: a cohort-based study.

BACKGROUND: The present study investigated the relationships between psychological stress indices and oxidative stress marker, also when combined with emergent insulin resistance (IR), in the non-diabetic, middle-aged subjects, exposed to frequent/chronic psychological stressors. METHODS: Cross-sectional data from a cohort of non-diabetic police officers (n = 234; 19F), aged 27-56 years, were used. Plasma inflammatory (CRP, TNF-α), oxidative stress (free 8-iso-prostaglandin F2α; 8-iso-PGF2α) markers, and insulin were measured. The value of homeostasis model assessment of IR index (HOMA-IR) was assumed the threshold value of IR, i.e. 2.04. Free cortisol in urine and perceived stress (psychological stress indices) were also measured. RESULTS: In the IR subjects, most biochemical variables, inflammatory markers and urine cortisol were significantly higher, as compared to the non-IR ones. Psychological stress indices were associated with plasma 8-iso-PGF2α [B = 0.139, 95% CI (0.048, 0.230), p = 0.002, and B = 0.007, 95% CI (0.0006, 0.014), p = 0.03; for perceived stress level and cortisol, respectively]. Positive associations were established between plasma 8-iso-PGF2α [B = 0.069, 95% CI (0.016-0.120), p = 0.01] and urine cortisol [B = 0.003, 95% CI (0.0003, 0.005), p = 0.02] with HOMA-IR. Metabolic syndrome, as defined by IDF criteria, was established in 110 study subjects, whereas 136 of them were hypertensive. Waist circumference [B = 0.056, 95% CI (0.039, 0.074), p < 0.0001], and systolic blood pressure [B = 0.009, 95% CI (0.00003, 0.018), p = 0.04] were positively associated with HOMA-IR, whereas the association of HDL cholesterol [B = - 0.597, 95% CI (- 1.139, - 0.055), p = 0.03] was a negative one. Cortisol [OR = 1.007, 95% CI (1.002, 1.012), p = 0.006], and 8-iso-PGF2α [OR = 1.103, 95% CI (1.010, 1.201), p = 0.02] affected the incidence of IR. After adjustment for metabolic syndrome (or its components), age, sex, and current smoking, the effects became non-significant. Out of metabolic syndrome components, waist circumference [OR 4.966, 95% CI (2.29, 10.751), p = 0.00004] and hypertriglyceridemia [OR 1.993, 95% CI (1.063, 3.736), p = 0.03] increased the chance of IR incidence. CONCLUSIONS: Both psychological stress indices were associated with oxidative stress, but only cortisol with HOMA-IR. In the subjects exposed to frequent/chronic psychological stressors, cortisol and oxidative stress marker affected IR incidence, being statistically attenuated, though, following adjustment for metabolic syndrome, or its components.

Clinical outcomes and plasma clot permeability and lysability in patients with venous thromboembolism on rivaroxaban: a cohort study.

INTRODUCTION: Denser fibrin structure and impaired fibrinolysis reported in patients following venous thromboembolism (VTE) can predict recurrent VTE after cessation of anticoagulation. OBJECTIVES: The aim of the study was to investigate whether the properties of fibrin clot may be useful in predicting adverse events in patients with VTE receiving rivaroxaban. PATIENTS AND METHODS: In 132 patients with VTE treated with rivaroxaban for 8 weeks or longer, we determined plasma clot permeability (Ks) and clot lysis time (CLT) in blood samples collected 2 to 28 hours after rivaroxaban intake (20 mg/d). The primary endpoint was a composite of major and clinically relevant nonmajor bleeding, while the secondary endpoint was recurrent symptomatic VTE. RESULTS: During a median follow­ up of 32 months, the annual rates of primary and secondary endpoints were 3.6% and 2.7%, respectively. There were no differences in Ks and CLT between individuals who experienced the primary endpoint and the remainder. Patients with recurrent VTE had lower baseline Ks (-26.7%) and prolonged CLT (+20.8%) on rivaroxaban, without differences in rivaroxaban concentrations at the time of blood collection. After adjustment for confounding factors, Ks was the only predictor of VTE recurrence on rivaroxaban (odds ratio, 0.23; 95% CI, 0.06-0.94). CONCLUSIONS: Our study suggests that Ks assessed on rivaroxaban may provide prognostic information about the risk of recurrent VTE in anticoagulated patients.

High detection rates of antithrombin deficiency and antiphospholipid syndrome in outpatients aged over 50 years using the standardized protocol for thrombophilia screening.

INTRODUCTION: Thrombophilia screening has limited detection efficiency. We assessed the detection rate when a standardized approach to thrombophilia-screened outpatients was used. METHODS: We analyzed 1185 patients (36.5% males, median age: 43 years [IQR 33-54]) referred to a single center from January 2014 to October 2017 with 11 different clinical indications for thrombophilia screening, which was performed in the adherence to published guidelines. Factor V Leiden, prothrombin G20210A mutation, antithrombin (AT), protein C, protein S deficiencies and antiphospholipid syndrome (APS) were determined. RESULTS: The overall positivity rate was 37.1% (95% CI 34.3%-39.7%). The highest positivity rate was found in women following VTE during pregnancy/childbirth (64.1%) and provoked VTE patients with positive family history (52.9%). In patients aged >50 years (32.5%), APS was found at a similar rate as in younger subjects (11.4% vs 10.1%), while AT deficiency was detected more frequently in the older group (5.7% vs 2.4%, p = 0.003). CONCLUSIONS: Standard indications for thrombophilia screening lead to detection rates of 37% or more. Frequent detection of APS and AT deficiency among older patients, which often implies a need for long-term anticoagulation and could impact clinical practice patterns, suggests a benefit of thrombophilia screening in this population in selected clinical circumstances.

Altered Plasma Clot Properties and Trauma-Related Venous Thromboembolism despite Thromboprophylaxis.

BACKGROUND: Prothrombotic clot phenotype may characterize patients developing deep vein thrombosis (DVT) despite pharmacological thromboprophylaxis. We studied the role of fibrin clot properties and its potential determinants in individuals who experienced DVT after lower limb injury. METHODS: In a case-control study, we assessed 50 patients who developed DVT despite prophylactic use of low-molecular-weight heparins (the failed thromboprophylaxis group) after a lower limb injury, and three age- and sex-matched control groups, 50 patients each: (1) patients with trauma-related DVT without prior thromboprophylaxis; (2) individuals with unprovoked DVT; (3) patients without history of DVT (the no-DVT controls). Fibrin clot properties, along with thrombin concentration and α2-antiplasmin, were assessed following 3 months of anticoagulation in all DVT patients. RESULTS: Compared with the no-DVT controls, the failed thromboprophylaxis group exhibited denser fibrin networks (12.8% lower clot permeability [Ks], p = 0.0008) and impaired fibrinolysis (46.2% longer clot lysis time [CLT], p = 0.0001 and 8% lower rate of D-dimer release from clots, p = 0.0008). In the unprovoked DVT, similar Ks and 14.9% shorter CLT (p = 0.02) were reported compared with the failed thromboprophylaxis group. The failed thromboprophylaxis patients had higher odds of having elevated peak thrombin generation (>241.5 nM, 90th percentile in the no-DVT controls; odds ratio [OR]: 3.62; 95% confidence interval [CI], 1.86-7.06; p = 0.002), and higher odds of having elevated α2-antiplasmin (>115.05%; OR: 3.38; 95% CI, 1.64-6.98; p = 0.001). CONCLUSION: Patients who experienced DVT despite thromboprophylaxis following lower limb trauma display a strongly prothrombotic fibrin clot phenotype, including increased clot density and hypofibrinolysis associated with higher plasma α2-antiplasmin.

Sternal wound infections following cardiac surgery and their management: a single-centre study from the years 2016-2017.

INTRODUCTION: Despite improvements in surgical management, sternal wound infection (SWI) following cardiac surgery remains a significant complication. AIM: To evaluate pathogens involved in SWI following median sternotomy. MATERIAL AND METHODS: We enrolled 164 patients who experienced prolonged sternal wound healing following open-heart surgery. The inclusion criteria were as follows: prolonged sternal wound healing following cardiac surgery via median sternotomy and complete results of microbiological culture obtained from the sternal swab. The exclusion criteria were as follows: partial sternotomy, patients with mechanical sternum dehiscence and incomplete clinical data. Swabs provided information on the type of microorganism present in the wound and the susceptibility of the microorganism to specific antibiotics. RESULTS: One hundred and fourteen (69.5%) patients aged 68 (interquartile range: 60-76) years developed SWI with positive culture. The in-hospital mortality rate was 21.0% in this group. The most common pathogens included Staphylococcus epidermidis (26.6%), Enterococcus faecium (12.2%), Staphylococcus aureus (11.4%), Klebsiella pneumoniae (8.4%), and Pseudomonas aeruginosa (6.8%). In most of the cases the isolated Staphylococcus epidermidis was methicillin-resistant (n = 57, 43.5%). Enterococcus faecium was vancomycin-resistant in 11 (8.3%) cases and high-level aminoglycoside resistant (HLAR) in 13 (9.9%) cases. Klebsiella pneumoniae had the extended-spectrum ß-lactamase (ESBL) mechanism in 14 (10.6%) cases. Among 114 culture-positive patients, 48 (42.1%) had polymicrobial infection of the sternal wound. CONCLUSIONS: Microorganisms associated with SWI in our study were mainly commensals, with the most common pathogen being Staphylococcus epidermidis.

Plasma fibrin clot properties in the G20210A prothrombin mutation carriers following venous thromboembolism: the effect of rivaroxaban.

We sought to investigate whether the G20210A prothrombin mutation modifies plasma fibrin clot properties in patients after venous thromboembolism (VTE) and how rivaroxaban treatment affects these alterations. We studied 34 prothrombin mutation heterozygous carriers and sex- and age-matched 34 non-carriers, all at least three months since the first VTE episode, before and during treatment with rivaroxaban. Clot permeability (Ks) and clot lysis time (CLT) with or without elimination of thrombin activatable fibrinolysis inhibitor (TAFI) were assessed at baseline, 2-6 hours (h) after and 20-25 h after intake of rivaroxaban (20 mg/day). At baseline, the prothrombin mutation group formed denser clots (Ks -12 %, p=0.0006) and had impaired fibrinolysis (CLT +14 %, p=0.004, and CLT-TAFI +13 %, p=0.03) compared with the no mutation group and were similar to those observed in 15 healthy unrelated prothrombin mutation carriers. The G20210A prothrombin mutation was the independent predictor for Ks and CLT before rivaroxaban intake. At 2-6 h after rivaroxaban intake, clot properties improved in both G20210A carriers and non-carriers (Ks +38 %, and +37 %, CLT -25 % and -25 %, CLT-TAFI -20 % and -24 %, respectively, all p<0.001), but those parameters were worse in the prothrombin mutation group (Ks -12.8 %, CLT +17 %, CLT-TAFI +13 %, all p<0.001). Rivaroxaban concentration correlated with fibrin clot properties. After 20-25 h since rivaroxaban intake most clot properties returned to baseline. Rivaroxaban-related differences in clot structure were confirmed by scanning electron microscopy images. In conclusion, rivaroxaban treatment, though improves fibrin clot properties, cannot abolish more prothrombotic fibrin clot phenotype observed in prothrombin mutation carriers following VTE.

Molecular profiling of murine sensory neurons in the nodose and dorsal root ganglia labeled from the peritoneal cavity.

Vagal afferent neurons are thought to convey primarily physiological information, whereas spinal afferents transmit noxious signals from the viscera to the central nervous system. To elucidate molecular identities for these different properties, we compared gene expression profiles of neurons located in nodose ganglia (NG) and dorsal root ganglia (DRG) in mice. Intraperitoneal administration of Alexa Fluor-488-conjugated cholera toxin B allowed enrichment for neurons projecting to the viscera. Fluorescent neurons in DRG (from T10 to T13) and NG were isolated using laser-capture microdissection. Gene expression profiles of these afferent neurons, obtained by microarray hybridization, were analyzed using multivariate spectral map analysis, significance analysis of microarrays (SAM) algorithm, and fold-difference filtering. A total of 1,996 genes were differentially expressed in DRG vs. NG, including 41 G protein-coupled receptors and 60 ion channels. Expression profiles obtained on laser-captured neurons were contrasted to those obtained on whole ganglia, demonstrating striking differences and the need for microdissection when studying visceral sensory neurons because of dilution of the signal by somatic sensory neurons. Furthermore, we provide a detailed catalog of all adrenergic and cholinergic, GABA, glutamate, serotonin, and dopamine receptors; voltage-gated potassium, sodium, and calcium channels; and transient receptor potential cation channels present in afferents projecting to the peritoneal cavity. Our genome-wide expression profiling data provide novel insight into molecular signatures that underlie both functional differences and similarities between NG and DRG sensory neurons. Moreover, these findings will offer novel insight into mode of action of pharmacological agents modulating visceral sensation.

Vagal influences over mast cells.

The established microanatomical association of rat intestinal mucosal mast cells (IMMC) and mucosal nerves raises the possibility that there is crosstalk between mast cells and extrinsic nerves that connect to the CNS. The idea of mast cell-CNS interactions is supported by the demonstration that rat mast cell protease II (RMCPII), found predominantly in IMMC, can be conditionally released by pairing an audio-visual cue with antigen challenge. That the vagus nerve is involved in the IMMC-nerve axis was further demonstrated in a series of our studies showing that: (a) vagal afferents penetrate the small intestinal mucosa and contact IMMC; (b) vagotomy causes a reduction in IMMC density, suggesting a trophic relationship (typical of nerve-target interactions); and (c) stimulation of the cervical vagus causes an increase in histamine and serotonin in IMMC. To further investigate the IMMC-nerve axis in a model of post-inflammatory bowel disorders, infection with Nippostrongylus brasiliensis (Nb) was used to demonstrate an increase in mast cell numbers in the intestinal mucosa and mucosal nerve remodelling with hyperinnervation. Administration of Nb antigen resulted in dramatic increases in mesenteric afferent nerve firing in Nb infected rats, that was absent in sham animals. Moreover, challenge of post-Nb rats with 2-methyl-5HT caused increased mesenteric afferent firing, indicating that vagal afferent innervation remains intact in the post-infection state. These data suggest a functional connection between mast cells and extrinsic afferent nerves. Nb infection provides a useful model of altered communication between IMMCs, peripheral nerves and the CNS, as may occur in post-inflammatory disease states. Since a close anatomical relationship has also previously been demonstrated between nerves and IMMC in humans, further understanding the mast cell-nerve axis may be of critical importance in the development of treatments for various human disease states, including functional bowel disorders.

The Relationship of Metabolic Syndrome with Stress, Coronary Heart Disease and Pulmonary Function--An Occupational Cohort-Based Study.

BACKGROUND AND AIMS: Higher levels of stress impact the prevalence of metabolic syndrome (MetS) and coronary heart disease. The association between MetS, impaired pulmonary function and low level of physical activity is still pending assessment in the subjects exposed to stress. The study aimed to examine whether higher levels of stress might be related to MetS and the plaque presence, as well as whether MetS might affect pulmonary function. DESIGN AND METHODS: The study embraced 235 police officers (mean age 40.97 years) from the south of Poland. The anthropometrics and biochemical variables were measured; MetS was diagnosed using the International Diabetes Federation criteria. Computed tomography coronary angiography of coronary arteries, exercise ECG, measurements of brachial flow-mediated dilation, and carotid artery intima-media thickness were completed. In order to measure the self-perception of stress, 10-item Perceived Stress Scale (PSS-10) was applied. Pulmonary function and physical activity levels were also addressed. Multivariate logistic regression analyses were applied to determine the relationships between: 1/ incidence of coronary plaque and MetS per se, MetS components and the number of classical cardiovascular risk factors, 2/ perceived stress and MetS, 3/ MetS and pulmonary function parameters. RESULTS: Coronary artery atherosclerosis was less associated with MetS (OR = 2.62, 95%CI 1.24-5.52; p = 0.011) than with a co-existence of classical cardiovascular risk factors (OR = 5.67, 95% CI 1.07-29.85, p = 0.03; for 3 risk factors and OR = 9.05; 95% CI 1.24-66.23, p = 0.02; for 6 risk factors, respectively). Perceived stress increased MetS prevalence (OR = 1.07, 95% CI 1.03-1.13; p = 0.03), and impacted coronary plaque prevalence (OR = 1.05, 95% CI 1.001-1.10; p = 0.04). Leisure-time physical activity reduced the chances of developing MetS (OR = 0.98 95% CI 0.96-0.99; p = 0.02). MetS subjects had significantly lower values of certain pulmonary function parameters. CONCLUSIONS: Exposure to job-specific stress among police officers increased the prevalence of MetS and impacted coronary plaque presence. MetS subjects had worse pulmonary function parameters. Early-stage, comprehensive therapeutic intervention may reduce overall risk of cardiovascular events and prevent pulmonary function impairment in this specific occupational population.

Alterations in the brain-gut axis underlying visceral chemosensitivity in Nippostrongylus brasiliensis-infected mice.

BACKGROUND & AIMS: Visceral hypersensitivity, a hallmark of irritable bowel syndrome, is generally considered to be mechanosensitive in nature and mediated via spinal afferents. Both stress and inflammation are implicated in visceral hypersensitivity, but the underlying molecular mechanisms of visceral hypersensitivity are unknown. METHODS: Mice were infected with Nippostrongylus brasiliensis (Nb) larvae, exposed to environmental stress and the following separate studies performed 3-4 weeks later. Mesenteric afferent nerve activity was recorded in response to either ramp balloon distention (60 mm Hg), or to an intraluminal perfusion of hydrochloric acid (50 mmol/L), or to octreotide administration (2 micromol/L). Intraperitoneal injection of cholera toxin B-488 identified neurons projecting to the abdominal viscera. Fluorescent neurons in dorsal root and nodose ganglia were isolated using laser-capture microdissection. RNA was hybridized to Affymetrix Mouse whole genome arrays for analysis to evaluate the effects of stress and infection. RESULTS: In mice previously infected with Nb, there was no change in intestinal afferent mechanosensitivity, but there was an increase in chemosensitive responses to intraluminal hydrochloric acid when compared with control animals. Gene expression profiles in vagal but not spinal visceral sensory neurons were significantly altered in stressed Nb-infected mice. Decreased afferent responses to somatostatin receptor 2 stimulation correlated with lower expression of vagal somatostatin receptor 2 in stressed Nb-infected mice, confirming a link between molecular data and functional sequelae. CONCLUSIONS: Alterations in the intestinal brain-gut axis, in chemosensitivity but not mechanosensitivity, and through vagal rather than spinal pathways, are implicated in stress-induced postinflammatory visceral hypersensitivity.

Interleukin-10 and nerve growth factor have reciprocal upregulatory effects on intestinal epithelial cells.

The intestinal mucosa is in a constant state of controlled inflammation, but the processes whereby this occurs are poorly understood. The aims of this study were to look at the role of IL-10 and nerve growth factor (NGF) in intestinal epithelial cell regulation. The human colon epithelial cell lines T84, HT-29, and CACO-2 were used. RT-PCR, flow cytometry analysis, and immunohistochemistry were applied to measure the cytokine changes in epithelial cells induced by recombinant cholera toxin and its B subunit, IL-10, and NGF. Cholera toxin B subunit caused selective dose-dependent increased mRNA for IL-10 in T84 cells and the protein in T84, HT-29, and CACO-2 cells. IL-10 dose dependently selectively increased NGF mRNA in T84 cells and intracellular protein synthesis in all three epithelial cell lines. The effect of NGF was reciprocal, selective, and dose dependent because it increased mRNA for IL-10 and IL-10 synthesis. Our results suggest that the epithelium may actively participate in downregulation through innate mechanisms involving IL-10 and NGF. The reciprocal interaction suggests for the first time that NGF may be involved in local downregulation by mucosal epithelium and thus may play a potent protective role in response to injury, by prevention of undue inflammation.