Geriatric nutritional risk index as the prognostic factor in older patients with fragility hip fractures.

This study investigated the long-term survival and incidence of secondary fractures after fragility hip fractures. The 5-year survival rate was 62%, and the mortality risk was seen in patients with GNRI < 92. The 5-year incidence of secondary fracture was 22%, which was significantly higher in patients with a BMI < 20. BACKGROUND: Malnutrition negatively influences the postoperative survival of patients with fragility hip fractures (FHFs); however, little is known about their association over the long term. OBJECTIVE: This study evaluated the ability of the geriatric nutritional risk index (GNRI) as a risk factor for long-term mortality after FHFs. METHODS: This study included 623 Japanese patients with FHFs over the age of 60 years. We prospectively collected data on admission and during hospitalization and assessed the patients' conditions after discharge through a questionnaire. We examined the long-term mortality and the incidence of secondary FHFs and assessed the prognostic factors. RESULTS: The mean observation period was 4.0 years (range 0-7 years). The average age at the time of admission was 82 years (range 60-101 years). The overall survival after FHFs (1 year, 91%; 5 years, 62%) and the incidence of secondary FHFs were high (1 year, 4%; 5 years, 22%). The multivariate Cox proportional hazard analysis revealed the risk factors for mortality as older age (hazard ratio [HR] 1.04), male sex (HR 1.96), lower GNRI score (HR 0.96), comorbidities (malignancy, HR 2.51; ischemic heart disease, HR 2.24; revised Hasegawa dementia scale ≤ 20, HR 1.64), no use of active vitamin D3 on admission (HR 0.46), and a lower Barthel index (BI) (on admission, HR 1.00; at discharge, HR 0.99). The GNRI scores were divided into four risk categories: major risk (GNRI, < 82), moderate risk (82-91), low risk (92-98), and no risk (> 98). Patients at major and moderate risks of GNRI had a significantly lower overall survival rate (p < 0.001). Lower body mass index (BMI) was also identified as a prognostic factor for secondary FHFs (HR 0.88 [p = 0.004]). CONCLUSIONS: We showed that older age, male sex, a lower GNRI score, comorbidities, and a lower BI are risk factors for mortality following FHFs. GNRI is a novel and simple predictor of long-term survival after FHFs.

Videolaryngoscopy vs. flexible fibrescopy for tracheal intubation in patients with cervical spine immobilisation: a randomised controlled trial.

In patients with cervical spine immobilisation, tracheal intubation devices other than a direct laryngoscope are frequently used to facilitate tracheal intubation and avoid related complications. In this randomised controlled trial, we compared videolaryngoscopic and fibrescopic tracheal intubation in patients with a cervical collar. Tracheal intubation was performed using either a videolaryngoscope with a non-channelled Macintosh blade (n = 166) or a flexible fibrescope (n = 164) in patients having elective cervical spine surgery whose neck was immobilised with a cervical collar to simulate a difficult airway. The primary outcome was the first attempt success rate of tracheal intubation. Secondary outcomes were the overall success rate of tracheal intubation; time to tracheal intubation; use of additional airway manoeuvres; and incidence and severity of tracheal intubation-related airway complications. First attempt success rate was higher in the videolaryngoscope group than in the fibrescope group (164/166 (98.8%) vs. 149/164 (90.9%), p = 0.003). Tracheal intubation was successful within three attempts in all patients. Median (IQR [range]) time to tracheal intubation was shorter (50.0 (41.0-72.0 [25.0-170.0]) s vs. 81.0 (65.0-107.0 [24.0-178.0]) s, p < 0.001) and additional airway manoeuvres were less frequent (30/166 (18.1%) vs. 91/164 (55.5%), p < 0.001) in the videolaryngoscope group compared with the fibrescope group. The incidence and severity of intubation-related airway complications were not different between the two groups. When performing tracheal intubation in patients with a cervical collar, videolaryngoscopy with a non-channelled Macintosh blade was superior to flexible fibrescopy.

Onychopapilloma: its clinical, dermoscopic and pathologic features.

BACKGROUND: Onychopapilloma is a benign tumour of the nail bed and distal matrix and commonly presents as longitudinal erythronychia, longitudinal leukonychia or longitudinal melanonychia. Because onychopapilloma is rare, its clinical characteristics and dermoscopic findings have not been well investigated in Asia. OBJECTIVES: This study aimed to investigate the clinical characteristics and dermoscopic and pathologic findings of onychopapilloma in Korea. METHODS: We retrospectively reviewed the medical records and clinical/dermoscopic photographs of 39 patients diagnosed with onychopapilloma in the Pusan National University Hospitals (Busan and Yangsan) for 11 years (2010-2021). RESULTS: Among 39 patients, 23 (59.0%) were men, and 16 (41.0%) were women. The mean age was 46.1 (16-77) years. All lesions were single, and most of them were located on the fingers (92.3%), especially the thumb (66.7%). The most common clinical feature was longitudinal erythronychia (56.4%), and the most common dermoscopic finding was distal subungual hyperkeratosis (100%). We found two new dermoscopic features: macrolunula and trailing lunula along the longitudinal band. Among 18 patients who underwent surgical excision, only 6 (33.3%) showed typical acanthosis and papillomatosis on the nail bed. CONCLUSIONS: We found that Asian onychopapilloma has similar clinicodermoscopic findings to the Caucasian one, that is to say, longitudinal erythronychia and distal subungual hyperkeratosis were the most common nail change and dermoscopic finding, respectively. We propose two new dermoscopic features of onychopapilloma: macrolunula and trailing lunula along the longitudinal band.

Effect of dipeptidyl peptidase IV inhibitors, thiazolidinedione, and sulfonylurea on osteoporosis in patients with type 2 diabetes: population-based cohort study.

The population-based cohort study used the Korean National Health Insurance claims database to evaluate the effect of anti-diabetic drugs on osteoporosis. The use of DPP-IV inhibitors does not increase the risk of osteoporosis compared with the use of sulfonylureas in patients with type 2 diabetes mellitus, while a weak association was found between thiazolidinediones and increased risk of osteoporosis. PURPOSE: The current study aimed to evaluate the effect of dipeptidyl peptidase IV inhibitors (DPP-IVi), thiazolidinedione (TZD), and sulfonylurea (SU) on osteoporosis in patients with type 2 diabetes. METHODS: A population-based cohort study was conducted in the Republic of Korea using the Korean National Health Insurance claims database. Data from 2012 to 2017 for patients of 50-99 years of age who were prescribed DPP-IVi, TZD, or SU during 2013-2015 were extracted from the database. Based on pre-defined criteria, a total of 381,404 patients were analyzed after inverse probability of treatment weighting. The association between the study drugs and osteoporosis was estimated using Cox proportional hazards models. Data of 220,166 patients who were prescribed DPP-IVi, 18,630 who were prescribed TZD, and 142,608 patients who were prescribed SU were set. RESULTS: In the multivariate-adjusted analysis, the hazard ratio (HR) of osteoporosis in the DPP-IVi group was not significantly different from that of the SU group (HR: 0.97; 95% confidence interval (CI) 0.94-1.00), whereas the HR of osteoporosis in the TZD group was higher (HR: 1.13; 95% CI 1.06-1.20). In the subgroup analysis, the HRs of osteoporosis were higher with pioglitazone (HR: 1.14; 95% CI 1.06-1.23) in the TZD group and with glibenclamides (HR: 1.39; 95% CI 1.09-1.77) in the SU group, whereas drugs with lower HR in the DPP-IVi group were saxagliptin (HR: 0.93; 95% CI 0.87-0.99) and sitagliptin (HR: 0.93; 95% CI 0.89-0.97). CONCLUSION: DPP-IV inhibitors do not increase the risk of osteoporosis compared with sulfonylureas in patients with type 2 diabetes mellitus, while a weak association was found between thiazolidinediones and increased risk of osteoporosis.

Impact of perceived contraceptive policy changes on long acting reversible contraception dispensing trends.

OBJECTIVE: We observed the long-term trend of Long Acting Reversible Contraception (LARC) usage before and after the 2016 presidential election. METHODS: We observed the rate of LARC dispensed at a university student health centre in the 18 months preceding and 27 months following the 2016 U.S. presidential election which posed threat to contraception access. We applied a segmented regression model using two linear regression line segments to evaluate whether there is a time point where the trend of LARC dispensing changed. We fit the regression models with a breakpoint at month 0 (election month) and 3 months with a Locally Estimated Scatterplot Smoothing (LOESS) estimate with parameters obtained by estimating simple linear regression models separately below and above the breakpoint '0'. RESULTS: There were a total of 2067 LARC methods dispensed from May 2015 to February 2019. The average number of LARC methods dispensed before November 2016 was 38/month and increased to 51/month post-presidential election. The LARC dispense rate significantly increased each month (0.38, 1.74; 95% confidence level, p < 0.05) until a breakpoint at 6 months (standard error 4.11) post-election followed by slower decrease (-0.59/month, 95% confidence level: -1.37, 0.20; p=not significant). CONCLUSION: Our study is the first to report long-term trends (27 months post-election) in LARC uptake amidst the public discourse that suggested the end of a policy that provided LARC insurance coverage. Although this observational study cannot suggest causality, the findings could reflect actions taken to prevent unintended pregnancy in response to the event of uncertain national policy.

Comparison of dermoscopic features between congenital and acquired acral melanocytic nevi in Korean patients.

BACKGROUND: The dermoscopic patterns of acral melanocytic nevi (AMNs) are crucial in differentiating them from acral melanoma. Several studies have reported the dermoscopic patterns of acquired acral melanocytic nevi (AAMNs). However, few have investigated the dermoscopic patterns of congenital acral melanocytic nevi (CAMNs). OBJECTIVE: To compare the clinical and dermoscopic features of CAMNs and AAMNs. METHODS: The present study included 43 patients with CAMNs and 40 with AAMNs. We reviewed their medical records as well as their clinical and dermoscopic findings. RESULTS: Congenital acral melanocytic nevis were more asymmetrical than AAMNs (P = 0.002) and presented more frequently as comma-shaped (P = 0.005). Regarding dermoscopic findings, globular pattern (55.8%) was the most common feature of CAMNs, while parallel furrow pattern (37.5%) was the most common feature of AAMNs. The presence of fibrillar, globular, and parallel ridge patterns, and diffuse multi-component pigmentation differed significantly between the groups (P < 0.05). Furthermore, CAMNs showed melanoma-specific dermoscopic patterns, such as parallel ridge (18.6%) and diffuse multi-component pigmentation (25.6%). CONCLUSION: The dermoscopic patterns of CAMNs and AAMNs differed markedly. In terms of dermoscopic patterns, CAMNs resembled acral melanoma more often than AAMNs did.

Search for a Dark Matter-Induced Annual Modulation Signal in NaI(Tl) with the COSINE-100 Experiment.

We present new constraints on the dark matter-induced annual modulation signal using 1.7 years of COSINE-100 data with a total exposure of 97.7 kg yr. The COSINE-100 experiment, consisting of 106 kg of NaI(Tl) target material, is designed to carry out a model-independent test of DAMA/LIBRA's claim of WIMP discovery by searching for the same annual modulation signal using the same NaI(Tl) target. The crystal data show a 2.7 cpd/kg/keV background rate on average in the 2-6 keV energy region of interest. Using a χ-squared minimization method we observe best fit values for modulation amplitude and phase of 0.0092±0.0067 cpd/kg/keV and 127.2±45.9 d, respectively.

First Direct Search for Inelastic Boosted Dark Matter with COSINE-100.

A search for inelastic boosted dark matter (IBDM) using the COSINE-100 detector with 59.5 days of data is presented. This relativistic dark matter is theorized to interact with the target material through inelastic scattering with electrons, creating a heavier state that subsequently produces standard model particles, such as an electron-positron pair. In this study, we search for this electron-positron pair in coincidence with the initially scattered electron as a signature for an IBDM interaction. No excess over the predicted background event rate is observed. Therefore, we present limits on IBDM interactions under various hypotheses, one of which allows us to explore an area of the dark photon parameter space that has not yet been covered by other experiments. This is the first experimental search for IBDM using a terrestrial detector.

Autonomic function test in progressive lacunar infarction.

OBJECTIVE: Neurological progression is a major problem in managing the patients with acute lacunar infarction. The purpose of this was to investigate whether autonomic dysfunction is associated with neurological progression in patients with acute lacunar infarction. MATERIALS AND METHODS: The study comprised 60 patients with acute lacunar infarction. All enrolled subjects underwent autonomic function tests including the 30° head-up tilt test, Valsalva test, heart rate response to deep breathing, and sympathetic skin response. The primary endpoint is the neurological progression, and the secondary endpoint is the 3-month outcome. RESULTS: Increased initial National Institute of Health stroke scale (NIHSS), decreased time to admission from onset, decreased rise of heart rate in the 30° head-up tilt test, abnormal blood pressure response in the Valsalva test, and decreased rise of systolic blood pressure in stage IV of the Valsalva test are associated with neurological progression of acute lacunar infarction; an abnormal blood pressure response in the Valsalva test is significant in logistic regression analysis of neurological progression. Advanced age, increased initial NIHSS and modified Rankin scale, decreased expiration/inspiration ratio of heart rate to deep breathing, decreased rise of systolic blood pressure in stage IV of the Valsalva test, and neurological progression were associated with an unfavorable 3-month outcome; neurological progression was significant in logistic regression analysis of 3-month outcome. CONCLUSIONS: An abnormal blood pressure change in the Valsalva test is associated with neurological progression in patients with acute lacunar infarction, and neurological progression can induce an unfavorable 3-month outcome.

Progressive topological disorganization of brain network in focal epilepsy.

OBJECTIVE: Increasing evidence has suggested that epilepsy is a network disease. Graph theory is a mathematical tool that allows for the analysis and quantification of the brain network. We aimed to evaluate the influences of duration of epilepsy on the topological organization of brain network in focal epilepsy patients with normal MRI using the graph theoretical analysis based on diffusion tenor imaging. METHODS: We prospectively enrolled 66 patients with focal epilepsy (18/66 patients were newly diagnosed) and 84 healthy subjects. All of the patients with epilepsy had normal MRI on visual inspection. All of the subjects underwent diffusion tensor imaging that was analyzed using graph theory to obtain network measures. RESULTS: The measures of characteristic path length and small-worldness in the patients with focal epilepsy were significantly decreased, even after multiple corrections (P < .01). Moreover, the measures including mean clustering coefficient and global efficiency in the patients with epilepsy had strong tendency to decrease compared to those in healthy subjects (P = .0153 and P = .0138, respectively). When comparing the measures among the patients with newly diagnosed/chronic epilepsy and healthy subjects using ANOVA, the characteristic path length (P = .006), small-worldness (P = .032), and global efficiency (P = .004) were significantly different. In addition, the duration of epilepsy was negatively correlated with global efficiency (r = -.249, P = .0454). CONCLUSIONS: We newly found a progressive topological disorganization of the brain network in focal epilepsy. In addition, we demonstrated disrupted topological organization in focal epilepsy, shifting toward a more random state.

The importance of dermoscopy for the diagnosis of acquired bilateral telangiectatic macules: the angioid streak pattern reveals underlying chronic liver disease.

BACKGROUND: Acquired bilateral telangiectatic macules (ABTM) are a newly recognized disease entity, which manifest as multiple telangiectatic pigmented macules confined mostly to the upper arms. OBJECTIVES: To evaluate clinical and dermoscopic features in a group of 50 patients with ABTM and to determine the diagnostic usefulness of dermoscopy in ABTM. METHODS: Patients were selected from two tertiary teaching hospitals in Korea [Pusan National University Hospitals (Busan and Yangsan)]. Fifty patients (41 males and 9 females; mean age 48.1 years; range 26-78 years) with ABTM were included in the study. The dermoscopic findings were graded using a 4-point scale: none (0), mild (1), moderate (2) and severe (3). In addition, the results of 23 patients with and 27 patients without chronic liver disease (CLD) were compared to determine whether the presence of CLD affects dermoscopic findings. RESULTS: Three distinct dermoscopic patterns were observed; brown pigmentations, telangiectasia (linear-irregular vessels) and an angioid streak pattern. Brown pigmentation in the group without CLD had higher severity score than those in CLD group (mean score: 2.00 vs. 1.48, P = 0.033). However, mean telangiectasia severity score was higher in the CLD group (2.14 vs. 1.39, P < 0.001). The angioid streak pattern was more severe and more common in patients with CLD than in those without [1.37 vs. 0.35 (P < 0.001) and 63.0% vs. 26.1%, respectively]. CONCLUSIONS: Detailed observations with dermoscopy can provide first clues of the presence of ABTM and underlying chronic liver disease.

Alitretinoin can be a good treatment option for idiopathic recalcitrant trachyonychia in adults: an open-label study.

BACKGROUND: Trachyonychia can be refractory to conventional treatments including topical, intralesional or systemic corticosteroids, as well as cyclosporine and retinoids. Therefore, new treatment options are needed for recalcitrant trachyonychia. OBJECTIVE: To evaluate the efficacy and safety of oral alitretinoin for idiopathic recalcitrant trachyonychia. METHODS: A total of 21 adult patients with 210 nails affected by idiopathic recalcitrant trachyonychia were evaluated in this open-label prospective study. All patients took 30 mg of alitretinoin daily for at least 3 months. Clinical outcomes were assessed using the Physician Global Assessment (PGA) scale proposed by Park et al. (degree of roughness: 0, clear; 1, mild; 2, moderate; 3, marked; 4, severe) at baseline and 1, 3 and 6 months after treatment. RESULTS: After 1, 3 and 6 months of treatment, 74.3% (123/210), 98.1% (206/210) and 99.2% (119/120) of nails showed clinical improvement, respectively; 0% (0/210), 22.9% (48/210) and 69.2% (83/120) were completely free from nail abnormalities. The mean PGA score at baseline was 3.4, decreasing significantly to 2.7, 1.3 and 0.7 at 1, 3 and 6 months following treatment, respectively. LIMITATIONS: A small number of participants and lack of a control group were limitations. CONCLUSIONS: For the first time, this study evaluated the efficacy and safety of oral alitretinoin for idiopathic recalcitrant trachyonychia in adults. The results suggest that oral alitretinoin can be a good treatment option for adult patients with recalcitrant trachyonychia.

Antiviral activity of hypothiocyanite produced by lactoperoxidase against influenza A and B viruses and mode of its antiviral action.

Hypothiocyanite (OSCN-) is a natural component of human saliva and is produced by the lactoperoxidase (LPO)/thiocyanate/hydrogen peroxide (H2O2) system. OSCN- has been previously shown to exhibit antiviral activity against influenza viruses (IFV) A/H1N1/2009 and A/H1N2/2009 in vitro as well as antimicrobial and antifungal activities. We elucidated the antiviral activity of OSCN- against both IFV types A and B and the mode of its antiviral action. OSCN- was produced constantly at 900 ± 200 µmol/l in Na3PO4 buffer solution containing NaSCN and LPO in the presence of H2O2 as an original OSCN- solution. In a plaque reduction assay, IFV A/PR/8/34 (H1N1), A/Fukushima/13/43 (H3N2), B/Singapore/222/97, and B/Fukushima/15/93 were exposed to various concentrations of OSCN- for 0 to 30 min before adsorption to MDCK cells, and plaque formation was examined. OSCN- exhibited significant similar antiviral activities against all four viruses without cytotoxicity, and the EC50 values for them were from 57 ± 16 to 148 ± 27 µmol/l regardless of the exposure times. The exposure of MDCK cells to OSCN- before viral adsorption did not affect its anti-IFV activity (EC50: more than 450 µmol/l), but the exposure after viral adsorption affected it moderately (EC50: 380 ± 40 µmol/l). Moreover, the exposure of virus particles to OSCN- at 450 µmol/l did not affect the hemagglutinin activity of IFV in hemagglutination inhibition assay. These results suggest that the attachment of OSCN- to the viral envelope critically contributes to the mode of antiviral action of OSCN- without interfering with viral adsorption. Keywords: hypothiocyanite; influenza virus type A; influenza virus type B; lactoperoxidase; antiviral activity.

Enhanced Th2 cell differentiation and function in the absence of Nox2.

BACKGROUND: Patients with chronic granulomatous disease (CGD), whom inherit abnormal function of NADPH oxidase 2 (Nox2), suffer from hyperinflammatory responses in lung as well as bacterial and fungal infection. There have been studies to reveal the function of Nox2 in hyperinflammatory diseases, especially in asthma, but the exact role of Nox2 in asthma is still unclear and controversial. Therefore, we attempted to clarify the exact role of Nox2 in asthma, using various experimental asthma models. METHODS: Asthma phenotypes were analyzed in response to various allergen-induced experimental asthma using Nox2-deficient mice and recombinase gene-activating-1-deficient mice. To understand the underlying mechanisms of exaggerated Th2 effector functions, we investigated the degree of T-cell activation, levels of activation-induced cell death (AICD), and regulatory T (Treg)-cell differentiation in Nox2-deficient T cells. RESULTS: Asthma phenotypes were increased through enhanced Th2 differentiation and function in Nox2-null mice regardless of dose and route of various allergens. Nox2-deficient T cells also showed hyperactivation, reduced AICD, and diminished Treg-cell differentiation through increased AKT phosphorylation (T308/S473) and enhanced mitochondrial ROS production. CONCLUSION: Our findings indicate that Nox2 deficiency results in exaggerated experimental asthma, which is caused by enhanced Th2 effector function in a T-cell-intrinsic manner.

Effective connectivity in temporal lobe epilepsy with hippocampal sclerosis.

OBJECTIVE: We hypothesized that temporal lobe epilepsy (TLE) patients with and without hippocampal sclerosis (HS) showed differences in their limbic networks. This study aimed to evaluate the role of the thalamus in TLE patients with HS. MATERIALS AND METHODS: Twenty-nine TLE patients with HS and 30 controls were enrolled in this study. In addition, we included eight TLE patients without HS as a disease control group. Using whole-brain T1-weighted MRIs, we analyzed the volumes of the limbic structures, including the hippocampus, thalamus, and total cortex, with FreeSurfer 5.1. We also investigated the effective connectivity among these structures using SPSS Amos 21 based on these volumetric measures. Moreover, we quantified correlations between epilepsy duration and the volumes of these structures. RESULTS: There was a statistically significant effective connectivity from the hippocampus to the thalamus in TLE patients with HS. Moreover, the volumes of the left and right thalamus were negatively correlated with epilepsy duration (r=-.42, P=.0315 and r=-.52, P=.0062, respectively). However, neither TLE patients without HS nor normal controls had a significant effective connectivity from the hippocampus to the thalamus. CONCLUSIONS: The limbic networks of TLE patients with and without HS could be different, and the thalamus might play a critical role in TLE patients with HS.

Brain morphology in juvenile myoclonic epilepsy and absence seizures.

OBJECTIVE: We evaluated the differences in brain morphology among patients with juvenile myoclonic epilepsy according to the occurrence of absence seizures. MATERIALS AND METHODS: Twenty-one juvenile myoclonic epilepsy patients with (n = 6) and without (n = 15) absence seizures were enrolled. We analyzed whole-brain T1-weighted magnetic resonance imaging using FreeSurfer 5.1. Measures of cortical morphology, such as thickness, surface area, volume, and curvature, and the volumes of subcortical structures, the cerebellum, and cerebrum, were compared between the groups. Moreover, we quantified correlations between clinical variables and each measures of abnormal brain morphology. RESULTS: Compared to normal controls, patients without absence seizures demonstrated thinning of the cortical thickness in the right hemisphere, including the post-central, lingual, orbitofrontal, and lateral occipital cortex. Compared to normal controls, patients with absence seizures had more widespread thinning of the cortical thickness, including the right post-central, lingual, orbitofrontal, and lateral occipital cortexes as well as the right inferior temporal cortex. Additionally, the volume of cerebellar white matter in patients without absence seizures was significantly smaller than that in normal controls. Patients with absence seizures had a much smaller cerebellar white matter volume than normal controls or patients without absence seizures. Moreover, there was significantly positive correlation between the age of seizure onset and the volume of cerebellar white matter in patients with juvenile myoclonic epilepsy. CONCLUSIONS: We demonstrated that there were significant brain morphology differences in patients with juvenile myoclonic epilepsy according to the presence of absence seizures. These findings support the hypothesis that juvenile myoclonic epilepsy may be a heterogeneous syndrome.

Cerebral hemodynamics in orthostatic intolerance with normal head-up tilt test.

OBJECTIVES: Orthostatic hypotension (OH) and postural orthostatic tachycardia syndrome (POTS) are well-known causes of orthostatic intolerance (OI). In addition, there are OI patients who are characterized by the symptoms of OI and lack of abnormal findings in head-up tilt (HUT) test. The aim of this study was to determine the cerebral hemodynamic changes in HUT test of OI patients with normal HUT (OINH). MATERIALS AND METHODS: Two hundred and sixty-one OI patients and 50 healthy controls were enrolled in this study. All subjects underwent transcranial Doppler test while performing the HUT test. Forty-five patients had OH, 33 patients had POTS, and 183 patients had OINH. Blood pressures, heart rate, cerebral blood flow velocities (CBFVs), end-tidal carbon dioxide (ET-PCO2 ), cerebral critical closing pressure (CCP), cerebral perfusion pressure (CPP), and cerebral vascular resistance (CVR) were measured during HUT test. We compared the hemodynamic parameters of OINH with those of OH, POTS, and healthy controls. RESULTS: Reduced CBFVs, CPP, and ET-PCO2 and elevated CCP were observed in the HUT test of all four groups. CVR was reduced in three OI patients. The drops in systolic CBFV, CPP, and CVR of OINH patients were greater than those of healthy controls. The changes in parameters in the HUT test of OINH group were not different from those of OH and POTS groups except prominent decrements of CPP and CVR in OH group. CONCLUSION: Our findings suggest that OINH is true OI sharing the common pathomechanism of OH and POTS.

Exopolysaccharide fraction from Pediococcus pentosaceus KFT18 induces immunostimulatory activity in macrophages and immunosuppressed mice.

AIMS: Exopolysaccharide fraction from Pediococcus pentosaceus KFT18 (PE-EPS), a lactic acid bacteria isolated from Kimchi (a Korean fermented vegetable product), was preliminary characterized and its immunostimulating effects were analysed. METHODS AND RESULTS: In this study, we used interferon-γ (IFN-γ)-primed RAW 264·7 macrophages and CD3/CD28-stimulated splenocytes to determine the immunotimulatory activities of PE-EPS. Upon exposure to PE-EPS, IFN-γ-primed RAW 264·7 macrophages showed significant increases in the expressions of inducible nitric oxide synthase (iNOS), tumour necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1ß. Molecular data using reporter gene assay and electrophoretic mobility shift assay (EMSA) revealed that PE-EPS upregulated transcriptional activity, DNA binding and the nuclear translocation of nuclear factor-κB (NF-κB). Furthermore, PE-EPS enhanced anti-CD3/CD28-specific proliferation and the productions of IL-2 and IFN-γ in primary splenocytes. In cyclophosphamide-induced immunosuppressed mice, pretreatment with PE-EPS (5, 15 or 45 mg kg(-1) day(-1), p.o.) increased thymus and spleen indices, and improved lymphocyte and neutrophil counts. CONCLUSION: PE-EPS stimulated the IFN-γ-primed macrophages and primary splenocytes to induce immune responses and improved the cyclophosphamide-induced immunosuppression in mice. SIGNIFICANCE AND IMPACT OF THE STUDY: The results in this study improved our understanding of immunostimulating activity of PE-EPS and supported its potential treatment option as a natural immunostimulant.

Influence of arm position on catheter placement during real-time ultrasound-guided right infraclavicular proximal axillary venous catheterization.

BACKGROUND: Real-time ultrasound-guided infraclavicular proximal axillary venous catheterization is used in many clinical situations and provides the advantages of catheter stabilization, a reduced risk of catheter-related infection, and comfort for the patient without limitation of movement. However, unintended catheter tip dislocation and accidental arterial puncture occur occasionally. This study was designed to investigate the influence of arm position on catheter placement and complications. METHODS: Patients were randomized to either the neutral group (n=240) or the abduction group (n=241). In the neutral group, patients were positioned with the head and shoulders placed in an anatomically neutral position and the arms kept by the side during catheterization. In the abduction group, the right upper arm was abducted at 90° from the trunk during catheterization. After real-time ultrasound-guided catheterization was carried out in the right infraclavicular proximal axillary vein, misplacement of the catheter and all complications were evaluated with ultrasound and chest radiography. RESULTS: The success rate of complete catheterization before evaluating the placement of the catheter was high in both groups (97.1 vs 98.8%, P=not significant). The incidence of accidental arterial puncture was not different (1.7 vs 0%, P=not significant). The incidence of misplacement of the catheter was higher in the neutral group than in the abduction group (3.9 vs 0.4%, P=0.01). There were no complications, such as haemothorax, pneumothorax, or injury to the brachial plexus and phrenic nerve, in either group. CONCLUSIONS: Upper arm abduction may minimize the risk of misplacement of the catheter during real-time ultrasound-guided infraclavicular proximal axillary venous catheterization. CLINICAL TRIAL REGISTRATION: The trial was registered with the Clinical Trial Registry of Korea: https://cris.nih.go.kr/cris/index.jsp. Identifier: KCT0001417.

The effect of sphingosine-1-phosphate on bone metabolism in humans depends on its plasma/bone marrow gradient.

BACKGROUND: Although recent studies provide clinical evidence that sphingosine-1-phosphate (S1P) may primarily affect bone resorption in humans, rather than bone formation or the osteoclast-osteoblast coupling phenomenon, those studies could not determine which bone resorption mechanism is more important, i.e., chemorepulsion of osteoclast precursors via the blood to bone marrow S1P gradient or receptor activator of NF-κB ligand (RANKL) elevation in osteoblasts via local S1P. AIM: To investigate how S1P mainly contributes to increased bone resorption in humans, we performed this case-control study at a clinical unit in Korea. METHODS: Blood and bone marrow samples were contemporaneously collected from 70 patients who underwent hip surgery due to either osteoporotic hip fracture (HF) (n = 10) or other causes such as osteoarthritis (n = 60). RESULTS: After adjusting for sex, age, BMI, smoking, alcohol, previous fracture, diabetes, and stroke, subjects with osteoporotic HF demonstrated a 3.2-fold higher plasma/bone marrow S1P ratio than those without HF, whereas plasma and bone marrow S1P levels were not significantly different between these groups. Consistently, the risk of osteoporotic HF increased 1.38-fold per increment in the plasma/bone marrow S1P ratio in a multivariate adjustment model. However, the odds ratios for prevalent HF according to the increment in the plasma and bone marrow S1P level were not statistically significant. CONCLUSION: Our current results using simultaneously collected blood and bone marrow samples suggest that the detrimental effects of S1P on bone metabolism in humans may depend on the S1P gradient between the peripheral blood and bone marrow cavity.