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Huijuan Hao

and 12 more

Background: Many patients with mild asthma are undiagnosed and untreated for low diagnostic sensitivity of the bronchodilation test (BDT). Objective: Investigating whether airway reversibility in BDT alone or together with fractional exhaled nitric oxide (FENO) can predict the response to anti-asthma therapy (RAT) in suspected asthma patients. Methods: This study included patients with chronic recurrent asthma symptoms, normal forced expiratory volume in 1 second (FEV1), and negative BDT. Inhaled corticosteroid (ICS) and long-acting β agonist (LABA) were given for 4 weeks. Positive RAT (PRAT) was defined as improved symptoms and increase of FEV1 > 200 mL after ICS/LABA. Lung tissues from 19 patients with lung nodules, grouped by predicted RAT, were also analyzed. Results: Of 102 patients, the PRAT group had higher FENO and greater absolute (∆) and (∆%) percent improvements of forced vital capacity, FEV1, and forced expiratory flows (FEFs) in BDT than the negative RAT group. The AUCs of FENO, ∆FEV1%, ∆FEF25-75%, and ∆FEF75% for PRAT were 0.703, 0.824, 0.736, and 0.710, with the optimal cut-off values of 33 ppb, 3.50%, 15.26%, and 26.04%. A joint model of FENO and ∆FEV1% increased the AUC to 0.880. IL-4, IL-5, IL-13, and NFκB were higher in lung tissues of patients with predicted PRAT than with predicted NRAT. Conclusion: ∆FEV1% > 3.50% in BDT together with FENO > 33 ppb predicted PRAT and an asthma diagnosis in patients with normal FEV1 and negative BDT. Evidence of pathological changes in the early stage of asthma increased the credibility of the predictive model.

Hui-Shan Hsieh

and 13 more

Abstract: Introduction: Efficacious screening of severe obstructive sleep apnea (OSA) is important for children with sleep-disordered breathing before time-consuming nocturnal polysomnography. However, the predictive performance of clinical variables, nocturnal unattended pulse oximetry, and snoring sound analysis to screen for severe pediatric OSA has not been comprehensively investigated. Methods: Forty-two consecutive children (11 [26%] girls and 31 [74%] boys; median age, 9 years; median body-mass index of 19.0 kg/m2) with loud snoring were prospectively recruited to undergo standard polysomnography, nocturnal pulse oximetry, and snoring sound analysis. Results: Binary logistic regression models showed that oxygen desaturation index ≥ 3% (> 5.9 events/h), adenoidal‐nasopharyngeal ratio (> 0.782), snoring sound energy of 801-1000 Hz (> 22.1 dB), and tonsil size (> 3) significantly predicted severe OSA, in descending order of odds ratio. Multivariate analysis showed that oxygen desaturation index ≥ 3%, adenoidal‐nasopharyngeal ratio, and tonsil size independently predicted severe OSA, and that their combination best predicted severe OSA (sensitivity = 91%; specificity = 84%; area under the curve = 0.92; p < 0.001). Conclusions: Our results suggested that pulse oximetry is better than snoring sound analysis to screen for severe OSA in children with loud snoring. A combination of oxygen desaturation index ≥ 3%, adenoidal‐nasopharyngeal ratio, and tonsil size can be used to efficiently screen for severe pediatric OSA.

Ruopeng Tan

and 8 more

Background and Purpose: Cancer patients treated with anthracyclines are susceptible to atrial fibrillation (AF) with unknown mechanisms. Due to sudden and unpredictable features of AF, detection or prediction of anthracycline-induced AF at early phase is difficult. Experimental Approach: Breast cancer patients (post-surgery) with an anthracycline-containing regimen were recruited for echocardiography at pre-, and 3 and 6 months post-chemotherapy. Mice were injected with doxorubicin or vehicle and the following parameters were determined: left atrial diameter, electrical transmission, AF inducibility. Meanwhile, oxidative stress, cardiomyocyte size, vacuolization, inflammation and fibrosis were measured in mouse atria. The therapeutic effect of dexrazoxane on doxorubicin-induced changes in the aforementioned parameters were also determined. Key Results: Whilst ventricular parameters and functions were unchanged in cancer patients pre- and post-chemotherapy, strain and strain rate of left atrial reservoir function and conduit function were decreased at 3 months post-chemotherapy vs pre-chemotherapy. Doxorubicin-induced atrial dilatation and susceptibility to AF occurred in mice prior to onset of ventricular dysfunction. Doxorubicin-induced AF was via inducing structural remodeling (i.e. cardiomyocyte death, hypotrophy and vacuolization) and electrical remodeling (i.e. reduction and redistribution of connexin 43) in the atrium, which was effectively prevented by dexrazoxane. Atrial remodeling and AF inducibility were induced after doxorubicin injection, which can be inhibited by dexrazoxane. Conclusions and Implications: Clinically, we tested whether anthracycline-induced early atrial remodeling in patients could be detected by echocardiography. Experimentally, we investigated the mechanisms of doxorubicin-induced atrial remodeling and AF in mice, and the protective effect of the free radical scavenger dexrazoxane.

nermeen hefila

and 3 more

ABSTRACT Nowadays , thrombophilia is one of the leading causes of RPL which has negative side effects due to psychological effect and the high expenses of investigations and attempts to get normal full term pregnancy up to ICSI trials in some cases. So as early as possible we try to diagnose the cause of abortion and treat it to avoid another bad experience of abortion. Aim of the work: to evaluate the correlation of factor V Leiden and MTHFR C677T gene mutation in primigravida late first trimester abortion and to identify candidates for anticoagulation therapy to improve pregnancy outcome .METHODOLOGY: polymerase chain reaction (PCR) and reverse-hybridization were used to assess MTHFR and FV leiden mutations . Results: MTHFR C 677T mutations were 42.5 %. While factor V leiden gene mutation were 20%. Combined MTHFR C 677T mutations and factor V leiden was 10 %, normal cases were 27.5%. The cases without MTHFR C 677Tgene mutations were 47.5% . While The cases with MTHFR C 677T mutations were 52.5%. Heterozygous MTHFR C 677T mutations cases were 37.5 % , homozygous cases were 15% .The cases without Factor V Leiden gene mutations were 70 %, cases with Factor V Leiden mutations were 30%. All cases with Factor V Leiden mutations were heterozygous and there was no homozygous cases. Conclusion: MTHFR mutation is highly expected in late first trimester missed abortions in primigravida specially the heterotype so significantly affect the pregnancy adversely while FACTOR V LEIDEN mutation is less likely to be found.

Mina Amiri

and 5 more

Objective To evaluate the total, and direct effects of vitamin D, measured by circulating 25-hydroxyvitamin D [25(OH)D] levels, on GWG after adjustment for confounding variables, and then assess the indirect effects by demonstrating the role of gestational age at birth as a mediator in this association. Design A secondary analysis of data collected in a screening program in pregnancy. Setting and population Data collected in “Khuzestan Vitamin D Deficiency Screening Program in Pregnancy” was used for the present study; it was included the data of 900 pregnant women referred to the health centers of Shushtar (Khuzestan Province, Iran), whose vitamin D status during the third trimester of pregnancy was available. Methods A mediation analysis was applied to detect the causal relationship between serum level of 25(OH)D, covariates (maternal age, parity, and baseline maternal weight), mediator (gestational age), and outcome (GWG). Main outcome measures The main outcome measure of the study was gestational weight gain. Results The adjusted total effect of vitamin D on GWG was estimated 0.0699 (95%CI: 0.0537, 0.0849; P=0.000). Although, an adjusted direct effect of vitamin D on GWG was not statistically significant, the adjusted indirect effect of this micronutrient on GWG by considering gestational age as a mediator was found to be significant [0.059 (95%CI: 0.048, 0.0708; P=0.000)]. Women with severe vitamin D deficiency had the lowest speed as compared to moderate and normal levels. Conclusion This study shows that maternal vitamin D status affects the gestational weight gain by reducing the risk of preterm delivery.
Recently, the survival of Mycobacterium bovis on livestock mineral blocks has been confirmed, but little is known about its implication in the transmission of animal tuberculosis (TB) under field conditions. The objective of this study was to describe the shared use of mineral supplements in four extensive beef cattle farms from a high TB prevalence area in South Central Spain, to identify the main factors explaining their use, and characterize its potential role for the transmission of Mycobacterium tuberculosis complex (MTC). This is relevant to design control measures at the wildlife-livestock interface. Animal activity was monitored by camera-trapping at 12 mineral supplementation points during spring and fall. Additionally, swabs were periodically taken from the mineral substrates and analyzed by PCR searching for MTC DNA. Cattle, pig, goat, sheep, wild boar and red deer were all recorded licking on mineral supplementation points. Livestock species were the main users and presented a diurnal use pattern. Wild ungulates presented a nocturnal-crepuscular use pattern, with scarce overlapping with livestock. Wild boar presence was positively related to cattle presence at mineral supplementation points, whereas red deer presence was higher in supplemental points closer to forested areas, mostly in absence of cattle. We recorded 266 indirect wildlife-livestock interactions (i.e. two consecutive visits that occurred within 78h), all of them derived from 21 unique wildlife visits. All the analyzed swabs resulted negative to MTC DNA. Comparing to other environmental sources of MTC in our study area, mainly water ponds, this research evidenced that mineral blocks are less attractive to wildlife. However, the potential for interspecific transmission of MTC or other pathogens cannot be discarded. The risk for interaction at mineral supplementation points and further transmission can be prevented by implementing specific measures in the context of integral biosecurity plans at the wildlife-livestock interface, which are proposed.

Motasem Suleiman

and 2 more

Group IV organometallic complexes are promising systems for C-H bond activation. We are interested in the C-H bond activation of the CH2 positions of the adamantyl group, since these positions are particularly hard to activate and to functionalize. As a potential platform for activation of that important alkyl group, we consider the alkyl bonded to the cyclopentadienyl in a substituted bis-cyclopentadienyl group IV metal diphenyl complex. The mechanism proposed in the classic paper reporting such activation using Zr(IV) (Erker and Mühlenbernd, 1987) involves an η2-benzyne complex intermediate. This current work reports a computational analysis of the problem through Density Functional Theory (DFT). We found that the two-step mechanism proposed for activation of C(Me)2-Ph or tert-Bu groups using Zr(IV) is indeed confirmed by DFT and that it can be extended to Ti and Hf. We further found that the system can be successfully extended to the adamantyl group. The first step involves formation of the benzyne complex, which can also be described as a metallacyclopropene. In the second step, the cyclopentadienyl-bound alkyl is activated in the coordination sphere of the metal via proton transfer to the bound benzyne, which, if the metallacyclopropene description is chosen, resembles a σ-bond metathesis. The C-H bond activation of adamantyl through this approach is thermodynamically and kinetically feasible. Selective α-CH bond activation should be achievable with Ti (under thermodynamic control), and selective γ-CH bond activation with Zr (under kinetic or thermodynamic control).

Kyoung-Hee Sohn

and 4 more

Background: For subjects who had previous hypersensitivity (HSR) to low-osmolar contrast media (LOCM), changing contrast media is recommended. However, determining the safest alternative LOCM is uncertain. We investigated the cross-reactivity among LOCMs and the outcomes of re-exposure in patients with previous immediate HSRs. Methods: The outcomes of re-exposure were assessed in the cohort with previous LOCM-associated HSR by the skin testing results and the presence of a common N-(2,3-dihydropoxypropyl) carbamoyl side chain. Results: Among 431 patients with previous HSR who underwent 482 skin tests, 250 cases (51.9%) showed positivity to intradermal tests, which was positively associated with the severity of HSR. The cross-reactivity among LOCMs was higher between LOCMs sharing common side chain compared to those not sharing (21.5% vs. 13.3%, P = .008). The recurrent HSRs was significantly reduced from 46.6% on re-exposure to culprit LOCM to 12.3% with changing LOCM based on the skin test results (P = .004). The overall recurrence rate was not further reduced when the LOCM was changed based on presence or absence of common side chain (15.1% vs. 11.8%, P = .428). However, for those who had severe index HSRs, skin test non-reactive LOCMs exposures, without the common side chain, resulted in a significant reduction in recurrent HSRs compared to LOCMs with the common side chain (24.0% vs. 7.8%, P = .049). Conclusion: In patients who experienced a severe index HSR to LOCM, avoidance of re-exposure to LOCMs with a common side chain or a positive skin test result is safer.
Background: Several medications may worsen heart failure (HF), and they are considered as potentially inappropriate medications for patients with heart failure (PIMHF). No studies have reported the prevalence of PIMHF use and its associated factors in Thai HF patients. Objective: To determine the prevalence of PIMHF use and identify the factors associated with PIMHF use. Materials and Methods: A cross-sectional analytical study was conducted using data on HF patients obtained from the electronic medical databases (EMD) of two hospitals, including a secondary- and a tertiary-care hospital. Data collected included demographics, diagnoses, and medication items prescribed during 2016–2019. The prevalence of PIMHF use identified by the Thailand list of PIMHF was determined. Patient and clinical factors were examined for association with PIMHF use by calculating the adjusted odds ratio (aOR) and 95% confidence interval (95% CI) using a binary logistic regression analysis. Results: From the EMD, 972 and 2,888 eligible HF patients from a secondary- and a tertiary-care hospital, respectively, were included in this study. The prevalence of PIMHF use was 45.16% and 33.07% at a secondary- and a tertiary-care hospital, respectively. The PIMHF distribution appeared similar between the two study hospitals, with oral corticosteroids being the most frequently prescribed, followed by NSAIDs, COX-2 inhibitors, and thiazolidinediones. The factors associated with PIMHF use were non-cardiovascular (non-CVD) co-morbidities, including diabetes mellitus (aOR = 1.68, 95%CI = 1.42–1.99), chronic pulmonary diseases (aOR = 2.69, 95%CI = 2.07–3.48), connective tissue diseases (aOR = 7.16, 95%CI = 3.09–16.57), and cancer (aOR = 1.97, 95%CI = 1.20–3.22). Conclusion: PIMHF use was prevalent in Thai HF patients and associated with certain non-CVD co-morbidities. A careful prescription and a review of medication use should focus on HF patients with specific non-CVD co-morbidities. Keywords: Heart failure; Potentially inappropriate medications; Thailand criteria; Prevalence; Factors associated

Carl Philpott

and 14 more

Background: Chronic rhinosinusitis (CRS) is a heterogenous group of inflammatory sinonasal disorders with key defining symptoms, but traditionally separated into phenotypes by clinical/endoscopic findings. It is not known if the two phenotypes have differing socioeconomic, co-morbidity and lifestyle differences. Objective: This analysis of the Chronic Rhinosinusitis Epidemiology Study (CRES) database sought to analyse any key differences in the socioeconomic variables between those with CRS with nasal polyps (CRSwNPs) and those without nasal polyps (CRSsNP). We also sought to analyse differences in comorbidities, lifestyle and quality of life. Methods: Patients with a confirmed diagnosis of CRS in secondary and tertiary care outpatient settings were invited to participate in a questionnaire based case-control study. Variables included demographics, comorbidities, socioeconomic factors, lifestyle factors and health related quality of life. Results: A total of 1204 patients’ data were analysed; 553 CRSsNP and 651 CRSwNP participants. The key socioeconomic variables did not demonstrate any notable differences, nor did lifestyle variables other than alcohol consumption being higher in those with CRSwNP (p=0.032). Aside from confirmation of asthma being more common in CRSwNP, it was notable that this group complained less of URTIs and CRSsNP participants showed evidence of lower HRQoL scores in respect of body pain (p=0.001). Conclusions: Patients with CRSwNP experience higher rates of asthma and lower rates of URTIs but otherwise do not demonstrate significant socioeconomic, comorbidity, lifestyle or quality of life issues other than for body pain and alcohol consumption.

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Gary Ghahremani

and 2 more

Summary Background: Torus is a protuberant and lobulated exostosis that develops on the lingual aspect of the jaws or hard palate in 10-30% of adults. They can interfere with mastication, speech, oral hygiene, and denture placement. Their enlargement with advancing age may also lead to superficial ulceration, inflammation, osteonecrosis and various other complications. Methods: A retrospective analysis of the authors’ experience with 17 adults who had large symptomatic tori was performed. The patients were examined by intraoral imaging and radiographic or computed tomography of their maxillofacial bones. Their dental and medical records were reviewed along with the pertinent literature concerning the prevalence and reported complications of this entity. Results: This series included 6 men and 11 women, ranging in age from 36 to 85 years (Mean age: 56.5 years).There were 6 patients with torus mandibularis, 8 with torus palatinus, and 3 with torus maxillaris. Four of our 17 patients required surgical excision of their tori because of large size, recurrent superficial erosions and associated symptoms. Conclusion: The majority of tori are asymptomatic and incidental finding, but the more prominent tori are prone to mucosal inflammation and ulceration that may require surgical removal of the lesion. Large tori can also interfere with mastication, speech, dental hygiene, placement and function of prosthetic dentures, and may cause snoring, sleep apnea or other complications. Therefore, the practicing physicians should be familiar with the appearance, radiological features, clinical implications and management of tori.

Wahaj Munir

and 3 more

Background: Acute type A aortic dissection (ATAAD), is a surgical emergency often requiring intervention on the aortic root. There is much controversy regarding root management; aggressively pursuing a root replacement, versus more conservative approaches to preserve native structures. Methods: Electronic database search we performed through PubMed, Embase, SCOPUS, google scholar and Cochrane identifying studies that reported on outcomes of surgical repair of ATAAD through either root preservation or replacement. The identified articles focused on short- and long-term mortalities, and rates of re-operation on the aortic root. Results: There remains controversy on replacing or preserving aortic root in ATAAD. Current evidence supports practice of both trends following an extensive decision-making framework, with conflicting series suggesting favourable results with both procedures as the approach that best defines higher survival rates and lower perioperative complications. Yet, the decision to perform either approach remains surgeon decision and bound to the extent of the dissection and tear entries in strong correlation with status of the aortic valve and involvement of coronaries in the dissection. Conclusions: There exists much controversy regarding fate of the aortic root in ATAAD. There are conflicting studies for impact of root replacement on mortality, whilst some study’s report no significant results at all. There is strong evidence regarding risk of re-operation being greater when root is not replaced. Majority of these studies are limited by the single centred, retrospective nature of these small sample sized cohorts, further hindered by potential of treatment bias.

Matthew Sussman

and 9 more

The recognition of fibrinolysis phenotypes in trauma patients has led to a reevaluation of antifibrinolytic therapy (AF). Many cardiac patients also receive AF, however the distribution of fibrinolytic phenotypes in that population is unknown. The purpose of this study was to fill that gap. Methods: Data were retrospectively reviewed from 78 cardiac surgery patients. Phenotypes were defined as hypofibrinolytic (LY30 <0.8%), physiologic (LY30 0.8-3.0%) and hyperfibrinolytic (LY30 >3%). Continuous variables were expressed as M ± SD or median (interquartile range). Results: The study population was 65±10 yrs old, 74% male, average body mass index of 29±5 kg/m2. Fibrinolytic phenotypes were distributed as physiologic=45%, hypo=32% and hyper = 23%. There was no obvious effect of age, gender, race, or ethnicity on the distribution of fibrinolysis phenotypes; 47% received AF. The time with chest tube during post-operative recovery was longer in those who received AF (4[3,5] days) vs no AF (3[2,4] days), P=0.037). All cause morbidity occurred in 51% of patients who received AF vs 25% with no AF (p=0.017). However, with AF vs no AF, apparent differences in median chest tube output (1379 vs 820ml, p=0.075), hospital LOS (13 vs 10 days, P=0.873), estimated blood loss (1100 vs 775 ml, P=0.127), units of transfused RBCs (4 vs 2], P=0.152) or all-cause mortality (5.4% [2/37] vs 10% [4/41], P=0.518) were not statistically significant. Conclusion: This is the first description of three distinctly different fibrinolytic phenotypes in cardiac surgery patients. In this population, the use of AF was associated with increased morbidity.

Arushi Singh

and 6 more

Background: Ibrutinib is associated with atrial fibrillation (AF), though echocardiographic predictors of AF have not been studied in this population. We sought to determine whether left atrial (LA) strain on transthoracic echocardiography could identify patients at risk for developing ibrutinib-related atrial fibrillation (IRAF). Methods: We performed a retrospective review of 66 patients who had an echocardiogram prior to ibrutinib treatment. LA strain was measured with TOMTEC Imaging Systems, obtaining peak atrial longitudinal strain (PALS) and peak atrial contraction strain (PACS) on 4-chamber and 2-chamber views. Statistical analysis was performed with Chi-square analysis, T-test, or binomial regression analysis, with a p-value < 0.05 considered statistically significant. Results: Twenty-two patients developed IRAF (33%). Age at initiation of ibrutinib was significantly associated with IRAF (65.1 years vs. 74.1 years, p = 0.002). Mean ibrutinib dose was lower among patients who developed IRAF (388.2 ± 121.7 vs. 448.6 ± 88.4, p = 0.025). E/e’ was significantly higher among patients who developed IRAF (11.5 vs. 9.3, p = 0.04). PALS was significantly lower in patients who developed AF (30.3% vs. 36.3%, p = 0.01). On multivariate regression analysis, age, PALS and PACS were significantly associated with IRAF. On multivariate regression analysis, only PACS remained significantly associated with IRAF while accounting for age. Conclusions: Age, ibrutinib dose, E/e’, and PALS on pre-treatment echocardiogram were significantly associated with development of IRAF. On multivariate regression analyses, age, PALS and PACS remained significantly associated with IRAF. Impaired LA mechanics add to the assessment of patients at risk for IRAF

Lacin Cevhertas

and 21 more

James Hummel

and 1 more

We thank Medina et al. for their interest in our recent work on QTc prolongation associated with treatment of COVID-19 patients with hydroxychloroquine and azithromycin. As they appropriately point out in their letter, genetic variation is likely a significant determinant of QT prolongation in the population at large and in COVID-19 patients specifically. While drugs causing acquired long QT syndrome and torsades de pointes are generally blockers of IKr, repolarization results from the aggregate of multiple inward and outward currents. Patients with sub-clinical defects in any of these ion channels can have normal or only slightly prolonged baseline QT intervals, but may possess decreased repolarization reserve leading to an exaggerated response to IKr blockade (1).  In our study, a baseline QTc of > 460 ms was associated with excessive QTc prolongation, and this likely represents a group of patients with sub-clinical cardiac ion channel mutations (so called “first hit”) (2). We also agree that many patients with latent mutations demonstrate a normal baseline QT, which gets prolonged with the addition of a drug or a change in the clinical condition “second hit” (3). The patients in our study who exhibited QTc prolongation were generally acutely ill, and displayed “multiple hits” that led to QTc prolongation and it is certainly plausible that many may have had sub-clinical cardiac ion mutations. We therefore wholeheartedly agree that pharmacogenetics should be considered in studies of drug-induced QT prolongation, however this information is rarely available to include for acutely ill patients. And while it makes sense to obtain genetic profiles prior to administration of QT-prolonging medications, that can only be performed in the elective outpatient setting, while taking into consideration medical, ethical and social issues related to asymptomatic genetic screening (e.g. cost, reimbursement, informed consent, etc…). There is significant interest in building genomic databases, and when this becomes a reality for the population at large we believe that genetic information should certainly be included in studies of QT prolongation.Roden DM Long QT syndrome: reduced repolarization reserve and the genetic link. J Intern Med. 2006 Jan; 259(1):59-69.Napolitano C, Schwartz PJ, Brown AM, et al. Evidence for a cardiac ion channel mutation underlying drug-induced QT prolongation and life-threatening arrhythmias. J Cardiovasc Electrophysiol. 2000;11:691–6Sauer AJ and Newton-Cheh C. Clinical and genetic determinants of torsade de pointes risk. Circulation. 2012;125:1684-94.

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