bluuebunny/crossref_metadata_2025 huggingface dataset:
Guidance for Studies Evaluating the Accuracy of Biomarker-Based Nonsputum Tests to Diagnose Tuberculosis
Authors: Drain Paul K , Gardiner Jennifer , Hannah Haylea , Broger Tobias , Dheda Keertan , Fielding Katherine , Walzl Gerhard , Kaforou Myrsini , Kranzer Katharina , Joosten Simone A , Gilpin Christopher , Weyer Karin , Denkinger Claudia M , Schumacher Samuel G
Published: August 2019

The World Health Organization’s (WHO) “End TB” strategy calls for development and implementation of novel tuberculosis (TB) diagnostics. Sputum-based diagnostics are challenging to implement and often less sensitive in high-priority populations. Nonsputum, biomarker-based tests may facilitate TB testing at lower levels of the healthcare system, accelerate treatment initiation, and improve outcomes. We provide guidance on the design of diagnostic accuracy studies evaluating nonsputum, biomarker-based tests within the context of WHO’s target product profile for such tests. Study designs should account for the intended use when choosing the study population, setting, and reference standards. Although adults with respiratory symptoms may be an initial target population, other high-priority populations regardless of symptoms—including people living with human immunodeficiency virus, those unable to produce sputum samples or with extrapulmonary TB, household contacts, and children—should be considered. Studies beyond diagnostic accuracy that evaluate feasibility and population-level impacts are also needed. A biomarker-based diagnostic may be critical to ending the TB epidemic, but requires appropriate validation before implementation.
Acute kidney injury after platinum-based transcatheter arterial chemoembolization and transarterial infusion chemotherapy in patients with hepatocellular carcinoma
Authors: Hayashi Manabu , Abe Kazumichi , Fujita Masashi , Okai Ken , Takahashi Atsushi , Ohira Hiromasa
Published: August 2019

Backgrounds

The incidence of acute kidney injury and the association between acute kidney injury and prognosis have been reported about transcatheter arterial chemoembolization using anthracycline. However, the incidence of acute kidney injury after platinum-based transarterial chemoembolization or transarterial infusion chemotherapy remains unclear. The aim of this study was to investigate association between acute kidney injury after platinum-based transcatheter arterial chemoembolization/transarterial infusion chemotherapy and prognosis in patients with hepatocellular carcinoma.

Methods

We retrospectively analysed 270 sessions in 129 patients who underwent platinum-based transcatheter arterial chemoembolization/transarterial infusion chemotherapy. Acute kidney injury was diagnosed according to the criteria established by the International Club of Ascites. The incidence of acute kidney injury, risk factors for serum creatinine elevation and association between acute kidney injury and prognosis were assessed.

Results

Fifteen cases of acute kidney injury (5.6%, 15/270) developed in 14 patients (10.8%, 14/129). Ascites (coefficient: 0.059, P = 0.006), low estimated glomerular filtration rate (coefficient: −0.008, P = 0.029), diabetes (coefficient: 0.072, P < 0.001) and high albumin–bilirubin grade (albumin–bilirubin grade 2: coefficient: 0.053, P = 0.004; and albumin–bilirubin grade 3: coefficient: 0.103, P < 0.001) were significantly associated with an elevation in serum creatinine levels after transcatheter arterial chemoembolization/transarterial infusion chemotherapy. The development of acute kidney injury was associated with poor prognosis (hazard ratio: 3.18, 95%CI: 1.411–7.171, P = 0.005). Patients with acute kidney injury had a significantly lower survival rate than patients without acute kidney injury (log-rank test; P = 0.034).

Conclusions

The incidence of acute kidney injury after platinum-based transcatheter arterial chemoembolization/transarterial infusion chemotherapy was consistent with that after transcatheter arterial chemoembolization using anthracycline, and the development of acute kidney injury was associated with poor prognosis. Ascites, diabetes, low estimated glomerular filtration rate and high albumin–bilirubin grade were risk factors for serum creatinine elevation after platinum-based transcatheter arterial chemoembolization/transarterial infusion chemotherapy.
Reprogramming and differentiation-dependent transcriptional alteration of DNA damage response and apoptosis genes in human induced pluripotent stem cells
Authors: Shimada Mikio , Tsukada Kaima , Kagawa Nozomi , Matsumoto Yoshihisa
Published: August 2019

Pluripotent stem cells (PSCs), such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), have a dual capability to self-renew and differentiate into all cell types necessary to develop an entire organism. Differentiation is associated with dynamic epigenetic alteration and transcriptional change, while self-renewal depends on maintaining the genome DNA accurately. Genome stability of PSCs is strictly regulated to maintain pluripotency. However, the DNA damage response (DDR) mechanism in PSCs is still unclear. There is accumulating evidence that genome stability and pluripotency are regulated by a transcriptional change in undifferentiated and differentiated states. iPSCs are ideal for analyzing transcriptional regulation during reprogramming and differentiation.

This study aimed to elucidate the transcriptional alteration surrounding genome stability maintenance, including DNA repair, cell cycle checkpoints and apoptosis in fibroblasts, iPSCs and neural progenitor cells (NPCs) derived from iPSCs as differentiated cells. After ionizing radiation exposure, foci for the DNA double-stranded break marker γ-H2AX increased, peaking at 0.5 h in all cells (>90%), decreasing after 4 h in fibroblasts (32.3%) and NPCs (22.3%), but still remaining at 52.5% (NB1RGB C2 clone) and 54.7% (201B7 cells) in iPSCs. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells were detected, indicating that iPSCs’ apoptosis increases. In addition, RNA sequencing (RNA-Seq) analysis showed high expression of apoptosis genes (TP53, CASP3 and BID) in iPSCs. Results suggested that increased apoptosis activity maintains accurate, undifferentiated genome DNA in the cell population.
Runaway merger shocks in galaxy cluster outskirts and radio relics
Authors: Zhang Congyao , Churazov Eugene , Forman William R , Lyskova Natalia
Published: August 2019

Moderately strong shocks arise naturally when two subclusters merge. For instance, when a smaller subcluster falls into the gravitational potential of a more massive cluster, a bow shock is formed and moves together with the subcluster. After pericentre passage, however, the subcluster is decelerated by the gravity of the main cluster, while the shock continues moving away from the cluster centre. These shocks are considered as promising candidates for powering radio relics found in many clusters. The aim of this paper is to explore the fate of such shocks when they travel to the cluster outskirts, far from the place where the shocks were initiated. In a uniform medium, such a ‘runaway’ shock should weaken with distance. However, as shocks move to large radii in galaxy clusters, the shock is moving down a steep density gradient that helps the shock to maintain its strength over a large distance. Observations and numerical simulations show that, beyond R500, gas density profiles are as steep as, or steeper than, ∼r−3, suggesting that there exists a ‘habitable zone’ for moderately strong shocks in cluster outskirts where the shock strength can be maintained or even amplified. A characteristic feature of runaway shocks is that the strong compression, relative to the initial state, is confined to a narrow region just behind the shock. Therefore, if such a shock runs over a region with a pre-existing population of relativistic particles, then the boost in radio emissivity, due to pure adiabatic compression, will also be confined to a narrow radial shell.
Searching for H i imprints in cosmic web filaments with 21-cm intensity mapping
Authors: Tramonte Denis , Ma Yin-Zhe , Li Yi-Chao , Staveley-Smith Lister
Published: August 2019

We investigate the possible presence of neutral hydrogen (H i) in intergalactic filaments at very low redshift (z ∼ 0.08), by stacking a set of 274 712 2dFGRS galaxy pairs over 21-cm maps obtained with dedicated observations conducted with the Parkes radio telescope, over a total sky area of approximately 1300 deg2 covering two patches in the northern and in the southern Galactic hemispheres. The stacking is performed by combining local maps in which each pair is brought to a common reference frame; the resulting signal from the edge galaxies is then removed to extract the filament residual emission. We repeat the analysis on maps cleaned removing either 10 or 20 foreground modes in a principal component analysis. Our study does not reveal any clear H i excess in the considered filaments in either case; we determine upper limits on the total filament H i brightness temperature at $T_{\rm b} \lesssim 10.3 \, \mu \text{K}$ for the 10-mode and at $T_{\rm b} \lesssim 4.8 \, \mu \text{K}$ for the 20-mode removed maps at the 95 per cent confidence level. These estimates translate into upper limits for the local filament H i density parameter, $\Omega _{\rm HI}^{\rm (f)} \lesssim 7.0\times 10^{-5}$ and $\Omega _{\rm HI}^{\rm (f)} \lesssim 3.2\times 10^{-5}$, respectively, and for the H i column density, $N_{\rm HI} \lesssim 4.6\times 10^{15}\, \text{cm}^{-2}$ and $N_{\rm HI} \lesssim 2.1\times 10^{15}\, \text{cm}^{-2}$, respectively. These column density constraints are consistent with previous detections of H i in the warm-hot intergalactic medium obtained observing broad Ly α absorption systems. This work shows for the first time how such constraints can be achieved using the stacking of galaxy pairs on 21-cm maps.
On the extraction of the power-law parts of probability density functions in star-forming clouds
Authors: Veltchev Todor V , Girichidis Philipp , Donkov Sava , Schneider Nicola , Stanchev Orlin , Marinkova Lyubov , Seifried Daniel , Klessen Ralf S
Published: August 2019

We present a new approach to extract the power-law part of a density/column-density probability density function (ρ-pdf/N-pdf) in star-forming clouds. This approach is based on the mathematical method bPlfit of Virkar & Clauset (2014, Annals of Applied Statistics, 8, 89) and it assesses the power-law part of an arbitrary distribution, without any assumptions about the other parts of this distribution. The slope and deviation point are derived as averaged values as the number of bins is varied. Neither parameter is sensitive to spikes and other local features of the tail. This adapted bPlfit method is applied to two different sets of data from numerical simulations of star-forming clouds at scales 0.5 and 500 pc, and it displays ρ-pdf and N-pdf evolution in agreement with a number of numerical and theoretical studies. Applied to Herschel data on the regions Aquila and Rosette, the method extracts pronounced power-law tails, consistent with those seen in simulations of evolved clouds.
Mechanism of Action and Biology of Flow Diverters in the Treatment of Intracranial Aneurysms
Authors: Ravindran Krishnan , Casabella Amanda M , Cebral Juan , Brinjikji Waleed , Kallmes David F , Kadirvel Ram
Published: August 2019

Flow diverters have drastically changed the landscape of intracranial aneurysm treatment and are now considered first-line therapy for select lesions. Their mechanism of action relies on intrinsic alteration in hemodynamic parameters, both at the parent artery and within the aneurysm sac. Moreover, the device struts act as a nidus for endothelial cell growth across the aneurysm neck ultimately leading to aneurysm exclusion from the circulation. In silico computational analyses and investigations in preclinical animal models have provided valuable insights into the underlying biological basis for flow diverter therapy. Here, we review the present understanding pertaining to flow diverter biology and mechanisms of action, focusing on stent design, induction of intra-aneurysmal thrombosis, endothelialization, and alterations in hemodynamics.
The availability of Beddoe relief in trust disputes—Lines v Wilcox [2019] EWHC 1451
Authors: Chandler Sam
Published: August 2019

An examination and discussion of the recent decision of the High Court (His Honour Judge Matthews) in Lines v Wilcox [2019] EWHC 1451 (Ch), concerning the availability of Beddoe relief in the context of proceedings involving trusts and estates. The fact pattern will be familiar to any practitioner in this field, and the decision is therefore of wide application. Specifically, the article considers the decision of the High Court to refuse Beddoe relief to an administrator of an estate who sought permission to prosecute a claim to set aside an inter vivos transfer of property made by the deceased in favour of a beneficiary named in her will.
The Customizable E-cigarette Resistance Influences Toxicological Outcomes: Lung Degeneration, Inflammation, and Oxidative Stress-Induced in a Rat Model
Authors: Cirillo Silvia , Vivarelli Fabio , Turrini Eleonora , Fimognari Carmela , Burattini Sabrina , Falcieri Elisabetta , Rocchi Marco Bruno Luigi , Cardenia Vladimiro , Rodriguez-Estrada Maria Teresa , Paolini Moreno , Canistro Donatella
Published: August 2019

Despite the knowledge gap regarding the risk-benefit ratio of the electronic cigarette (e-cig), its use has grown exponentially, even in teenagers. E-cig vapor contains carcinogenic compounds (eg, formaldehyde, acetaldehyde, and acrolein) and free radicals, especially reactive oxygen species (ROS) that cause toxicological effects, including DNA damage. The role of e-cig voltage customization on molecule generation has been reported, but the effects of the resistance on e-cig emissions and toxicity are unknown. Here, we show that the manipulation of e-cig resistance influences the carbonyls production from nonnicotine vapor and the oxidative and inflammatory status in a rat model. Fixing the voltage at the conventional 3.5 V, we observed that the amount of the selected aldehydes increased as the resistance decreased from 1.5 to 0.25 Ω. Under these conditions, we exposed Sprague Dawley rats to e-cig aerosol for 28 days, and we studied the pulmonary inflammation, oxidative stress, tissue damage, and blood homeostasis. We found a perturbation of the antioxidant and phase II enzymes, probably related to the increased ROS levels due to the enhanced xanthine oxidase and P450-linked monooxygenases. Furthermore, frames from scanning electron microscope showed a disorganization of alveolar and bronchial epithelium in 0.25 Ω group. Overall, various toxicological outcomes, widely recognized as smoke-related injuries, can potentially occur in e-cig consumers who use low-voltage and resistance device. Our study suggests that certain “tips for vaping safety” cannot be established, and encourages further independent investigations to help public health agencies in regulating the e-cig use.
p53 Activation by Cr(VI): A Transcriptionally Limited Response Induced by ATR Kinase in S-Phase
Authors: Luczak Michal W , Krawic Casey , Zhitkovich Anatoly
Published: August 2019

Cellular reduction of carcinogenic chromium(VI) causes several forms of Cr-DNA damage with different genotoxic properties. Chromate-treated cultured cells have shown a strong proapoptotic activity of the DNA damage-sensitive transcription factor p53. However, induction of p53 transcriptional targets by Cr(VI) in rodent lungs was weak or undetectable. We examined Cr(VI) effects on the p53 pathway in human cells with restored levels of ascorbate that acts as a principal reducer of Cr(VI) in vivo but is nearly absent in standard cell cultures. Ascorbate-restored H460 and primary human cells treated with Cr(VI) contained higher levels of p53 and its Ser15 phosphorylation, which were induced by ATR kinase. Cr(VI)-stimulated p53 phosphorylation occurred in S-phase by a diffusible pool of ATR that was separate from the chromatin-bound pool targeting DNA repair substrates at the sites of toxic mismatch repair (MMR) of Cr-DNA adducts. Even when more abundantly present than after exposure to the radiomimetic bleomycin, Cr(VI)-stabilized p53 showed a much more limited activation of its target genes in two types of primary human cells. No increases in mRNA were found for nucleotide excision repair factors and a majority of proapoptotic genes. A weak transcription activity of Cr(VI)-upregulated p53 was associated with its low lysine acetylation in the regulatory C-terminal domain, resulting from the inability of Cr(VI) to activate ATM in ascorbate-restored cells. Thus, p53 activation by ascorbate-metabolized Cr(VI) represents a limited genome-protective response that is defective in upregulation of DNA repair genes and proapoptotic transcripts for elimination of damaged cells.
Evaluation of antibody detection against the NDO-BSA, LID-1 and NDO-LID antigens as confirmatory tests to support the diagnosis of leprosy in Yunnan province, southwest China
Authors: Jian Liu , Xiujian Shang , Yuangang You , Yan Xing , Lianchao Yuan , Duthie Malcolm S , Yan Wen
Published: August 2019

Although multidrug therapy (MDT) has been widely used for the treatment of leprosy for nearly 40 y, the disease remains a public health concern in some areas. The early detection of leprosy cases is vital to interrupt Mycobacterium leprae transmission, but currently diagnosis is typically achieved during the recognition of clinical symptoms by professional staff performing physical examinations in conjunction with microbiological assessment of slit skin smears (SSSs) and histopathology. In the last 10 y, serum antibody detection tests have emerged to aid leprosy diagnosis. Here we evaluated the ability of antigens NDO-BSA and LID-1 (ML0405 and ML2331) and the conjugate of these, NDO-LID, to detect antibodies in the sera of 113 leprosy patients and 166 control individuals in Yunnan province in southwest China. We found that each antigen was readily detected by sera from multibacillary (MB) patients, with sensitivities of 97.3%, 97.3% and 98.6% for NDO-BSA, LID-1 and NDO-LID, respectively. Even among paucibacillary (PB) patients the antigens detected antibodies in 74.4%, 56.4% and 69.2% of serum samples, respectively. Receiver operating characteristics (ROC) curve analysis indicated that, irrespective of the leprosy case classification as MB or PB, the detection efficiency obtained with NDO-LID was better than that obtained with the other two antigens (with LID-1 being a slightly better than NDO-BSA). Our results indicate the utility of NDO-LID in assisting in the diagnosis of PB and MB leprosy patients and that these antibody detection assays represent powerful diagnostic tools. We suggest that could be implemented into the procedures of local health centres in leprosy-endemic regions to assist in earlier diagnosis.
Posttraumatic Stress Disorder and Incident Infections
Authors: Jiang Tammy , Farkas Dóra Körmendiné , Ahern Thomas P. , Lash Timothy L. , Sørensen Henrik T. , Gradus Jaimie L.
Published: August 2019

Background:

It is unknown whether posttraumatic stress disorder (PTSD) is associated with incident infections. This study’s objectives were to examine (1) the association between PTSD diagnosis and 28 types of infections and (2) the interaction between PTSD diagnosis and sex on the rate of infections.

Methods:

The study population consisted of a longitudinal nationwide cohort of all residents of Denmark who received a PTSD diagnosis between 1995 and 2011, and an age- and sex-matched general population comparison cohort. We fit Cox proportional hazards regression models to examine associations between PTSD diagnosis and infections. To account for multiple estimation, we adjusted the hazard ratios (HRs) using semi-Bayes shrinkage. We calculated interaction contrasts to assess the presence of interaction between PTSD diagnosis and sex.

Results:

After semi-Bayes shrinkage, the HR for any type of infection was 1.8 (95% confidence interval: 1.6, 2.0), adjusting for marital status, non-psychiatric comorbidity, and diagnoses of substance abuse, substance dependence, and depression. The association between PTSD diagnosis and some infections (e.g., urinary tract infections) were stronger among women, whereas other associations were stronger among men (e.g., skin infections).

Conclusions:

This study’s findings suggest that PTSD diagnosis is a risk factor for numerous infection types and that the associations between PTSD diagnosis and infections are modified by sex.
Orbital Reconstruction via Deformable Titanium Mesh Following Spheno-Orbital Meningioma Resection: Ophthalmic Presentation and Outcomes
Authors: Pace S. Tyler , Koreen Irina V. , Wilson John A. , Yeatts R. Patrick
Published: August 2019

The ophthalmic presentation of spheno-orbital meningioma and postoperative results are presented following description of orbital reconstruction utilizing deformable titanium mesh.

Purpose:

To present a surgical approach to reconstruction of the bony orbit following resection of spheno-orbital meningioma utilizing deformable titanium mesh while emphasizing the ophthalmic presentation and outcomes of the repair.

Methods:

A retrospective chart review received International Review Board approval, and 20 patients met the inclusion criteria. All patients underwent resection of spheno-orbital meningioma followed by orbital reconstruction with deformable titanium mesh. Pre- and postoperative ophthalmic exam findings were recorded. Outcome measures include Snellen visual acuity, performance on automated Humphry 30–2 perimetry, extraocular motility, Hertel exophthalmometry, associated complications, and recurrence. A literature review of the use of titanium to reconstruct the orbit following resection of spheno-orbital meningioma was performed.

Results:

Visual acuity improved (9/20) or remained the same (8/20) in 85% of patients. Fifteen of the 20 patients had pre- and postoperative visual fields performed, and 93% (14/15) experienced substantial improvement or no change with full fields. Of the 12 patients who had extraocular motility disturbance following surgery, 25% (3/12) had preexisting defects that did not change, 58% (7/12) returned to normal, and 17% (2/12) had new onset dysfunction that did not improve. Proptosis was reduced by a mean of 4.4 mm. Complications were rare and inconsequential, and recurrence was observed in 20% (4/20) at an average of 43 months following surgery.

Conclusions:

Orbital reconstruction using deformable titanium mesh is both safe and effective in the setting of resection of spheno-orbital meningioma. This study is the largest known report of orbits reconstructed with deformable titanium mesh in the available literature.
Nationwide Analysis of Resource Utilization and In-Hospital Outcomes in the Obese Patients With Lower Gastrointestinal Hemorrhage
Authors: Desai Jiten , Shah Yash , Patel Krunalkumar , Savani Sejal , Goyal Hemant , Desai Rupak , Patel Palakkumar , Doshi Rajkumar
Published: August 2019

Goals:

The goal of this study was to evaluate the impact of obesity on the outcomes of patients with lower gastrointestinal hemorrhage (LGIH).

Background:

Obesity is considered as an independent risk factor for LGIH. We sought to analyze in-hospital outcomes and characteristics of nonobese and obese patients who presented with LGIH, and further, identify resource utilization during their hospital stay.

Materials and Methods:

With the use of National Inpatient Sample from January 2005 through December 2014, LGIH-related hospitalizations (age≥18 y) were identified using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnostic codes. Patients were stratified into the nonobese and obese groups depending on their body mass index (>30 kg/m2). The statistical analyses were performed using SAS 9.4.

Results:

Of the total 482,711 patients with LGIH-related hospitalizations, 38,592 patients were found to be obese. In a propensity-matched analysis, the in-hospital mortality was higher in the nonobese patients (4.2% vs. 3.8%, P=0.004), however, the mean length of hospital stay and mean cost was higher in the obese group which could be due to a higher number of comorbidities in the obese group. Secondary outcomes such as the need for mechanical ventilation vasopressor use and colonoscopy was significantly higher in the obese group.

Conclusions:

The study results demonstrate that ‘obesity paradox’ do exist for LGIH-related hospitalizations for mortality. LGIH hospitalizations in the obese patients are associated with higher resource utilization as evidenced by the longer length of stay and higher cost of hospitalizations as compared with the nonobese patients.
Cost-related delay in filling prescriptions and health care ratings among medicare advantage recipients
Authors: Parikh Toral J. , Helfrich Christian D. , Quiñones Ana R. , Marshall-Fabien Gillian L. , Makaroun Lena K. , Black Marissa A. , Thielke Stephen M.
Published: August 2019

Despite higher health care needs, older adults often have limited and fixed income. Approximately a quarter of them report not filling or delaying prescription medications due to cost (cost-related prescription delay, CRPD). To ascertain the association between CRPD and satisfaction with health care, secondary analysis of the 2012 Consumer Assessment of Healthcare Providers and Systems (CAHPS) Medicare Advantage Survey was performed.

Regression models quantified the association between CRPD and rating of personal doctor, specialist, and overall health care. Models were adjusted for demographic, health-related, and socioeconomic characteristics. 274,996 Medicare Advantage enrollees were mailed the CAHPS survey, of which 101,910 (36.8%) returned a survey that had responses to all the items we analyzed. CRPD was assessed by self-report of delay in filling prescriptions due to cost. Health care ratings were on a 0-10 scale. A score ≤ 5 was considered a poor rating of care.

In unadjusted models, CRPD more than doubled the relative risk (RR) for poor ratings of personal doctor (RR 2.34), specialist (RR 2.14), and overall health care (RR 2.40). Adjusting for demographics and health status slightly reduced the RRs to 1.9, but adjusting for low-income subsidy and lack of insurance for medications did not make a difference.

CRPD is independently associated with poor ratings of medical care, regardless of health, financial or insurance status. Providers might reduce patients’ financial stress and improve patient satisfaction by explicitly discussing prescription cost and incorporating patient priorities when recommending treatments.
Are repetitive pericranial nerve blocks effective in the management of chronic paroxysmal hemicrania?
Authors: Ertem Devrimsel Harika
Published: August 2019

Introduction:

Paroxysmal hemicrania (PH) is a chronic headache disorder characterized by unilateral pain attacks accompanied by cranial autonomic symptoms and responds to indomethacin completely. There are few alternative treatment options for the patients who cannot tolerate indomethacin. Studies exploring the effects of repetitive peripheral cranial nerve blocks in the management of chronic PH are limited.

Patient concerns and diagnosis:

A 34-year-old woman with a 4-year history of PH was evaluated. Her pain was prevented by indomethacin without side effects; however, she wanted to try to conceive.

Interventions:

Repetitive pericranial nerve blocks, great occipital nerve, infraorbital nerve, supraorbital nerve, and sphenopalatine ganglion block, using local anesthetics and steroids were performed once a week for a 6 weeks period.

Outcomes:

A follow-up of 3 months showed that there was no pain relief following the injections and patient was needed to be maintained on indomethacin.

Conclusion:

Although pericranial nerve blocks have been tried in chronic PH cases with positive influences, this case indicated that repetitive nerve blocks were not always a successful therapy option.
Association between CYP1A1 rs4646903 T > C genetic variations and male infertility risk
Authors: Cao DeHong , Ren ZhengJu , Lu DongLiang , Liu LiangRen , Xu Peng , Zhang Qin , Wei Qiang
Published: August 2019

Background:

Number of studies have been performed to investigate the relationship between the CYP1A1 rs4646903 polymorphism and male infertility risk, but the sample size was small and the results were conflicting. A meta-analysis was performed to assess these associations.

Methods:

A systematic search was conducted to identify all relevant studies from Medline, Web of science, Embase, China biology medical literature database (CBM), China National Knowledge Infrastructure (CNKI), WanFang and Weipu (VIP) databases up to June 30, 2018. The odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of associations. All of the statistical analyses were conducted using Revman 5.3 and Stata 14.0.

Results:

Ten studies involved 3028 cases and 3258 controls. Overall, significant association was observed between the CYP1A1 rs4646903 polymorphism and male infertility (C vs T: OR = 1.42, 95%CI = 1.14–1.76; CC vs TT: OR = 2.13, 95%CI = 1.36–3.34; CC vs CT+TT: OR = 1.96, 95%CI = 1.30–2.95; CC+CT vs TT: OR = 1.51, 95%CI = 1.16–1.97). In subgroup analysis by ethnic group, a statistically significant association was observed in Asians (C vs T: OR = 1.59, 95%CI = 1.22–2.08), but not in Non-Asians (C vs T: OR = 1.01, 95%CI = 0.79–1.30). Additionally, none of the individual studies significantly affected the association between CYP1A1 rs4646903 polymorphism and male infertility, according to sensitivity analysis.

Conclusion:

Our meta-analysis supports that the CYP1A1 rs4646903 polymorphism might contribute to individual susceptibility to male infertility in Asians.
Predictive value of CHA2DS2-VASc scores regarding the risk of stroke and all-cause mortality in patients with atrial fibrillation (CONSORT compliant)
Authors: Gažová Andrea , Leddy John J. , Rexová Mária , Hlivák Peter , Hatala Róbert , Kyselovič Jan
Published: August 2019

Background:

Patients with atrial fibrillation (AF) have a higher risk of fatal complications (e.g., stroke). This investigation was performed as an observational retrospective cohort study includes 137 patients (age 61 ± 15; 34.3% women) with a primary diagnosis of AF (paroxysmal, persistent, and permanent).

Methods:

We collected information about the drug therapy, comorbidities and survival of AF patients and determined their congestive heart failure, hypertension, age, diabetes mellitus, prior stroke or TIA or thromboembolism, vascular disease, age, sex category (CHA2DS2-VASc) scores. Statistical analysis identified patients with high CHA2DS2-VASc scores and defined the predictive value of individual parameters, or their combination, with regards to the outcomes of stroke and mortality.

Results:

CHA2DS2-VASc scores identified 43.8% of the patients as low to intermediate risk (score 0–1) and 56.2% of the patients as high risk (score ≥2). Increasing CHA2DS2-VASc scores were not only accompanied by an increase in the incidence of stroke (P
trend < .001) but also by an increase in the 3 to 5 years mortality (P = .005). Comparison of anticoagulation and anti-aggregation treatment between the 3 groups of AF did not show any significant statistical difference. Highly significant predictors of death were the CHA2DS2-VASc score (OR 1.71, 95% CI 1.10–2.67, P < .017) as well as other risk factors not included in the CHA2DS2-VASc score such as valvular heart disease (OR 5.04, 95% CI 1.10-23.10, P = .037), hyperlipidemia (OR 4.82, 95% CI 1.03–22.63, P = .046) and chronic renal failure (OR 14.21, 95% CI 2.41–83.91, P = .003). The type of AF type did not affect survival (P = .158) nor the incidence of stroke (P = .466). Patients with paroxysmal AF were linked to significantly lower frequencies of ischemic heart disease (P < .0001), vascular disease (P = .002), diabetes mellitus (P = .047), valvular heart disease (P = .03) and heart failure/left ventricular dysfunction (P = .015).

Conclusion:

The CHA2DS2-VASc score correctly predicted the patients at high-risk for 3 to 5 years mortality and confirmed its significant predictive value in the patients with AF.
The efficacy, safety, and cost benefits of splints for fractures of the distal radius in children
Authors: Cui Xin , Liang Long , Wei Xu , Liao Xing , Li Yongyao , Cheng Hao , Xie Yanming , Cheng Yongzhong , Du Yachao , Liu Guangwei , Zhang Hongyan , Wang Shiheng , Liu Jiani , Wang Zhibo , Zhang Yue , Tian Yaliang
Published: August 2019

Background:

Distal radius fractures (DRFs) is one of the most common bone injuries in children, which may lead to deformity and other complications if the treatment is not prompt or appropriate. Splints external fixation is a common conservative treatment for such fractures. Therefore, we conducted a systematic review and meta-analysis to explore the efficacy, safety and cost benefits of splints in the treatment of DRFs in children.

Methods:

PubMed, Web of Science, Embase, Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov, Chinese National Knowledge Infrastructure Database (CNKI), Wanfang Database, and VIP Database were searched for eligible randomized controlled trials (RCTs). The methodological quality of the included studies and the level of evidence for results were assessed, respectively, using the risk bias assessment tool of Cochrane and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. Statistical analysis was conducted with Revman 5.3.

Results:

This study will analyze and integrate the existing evidence for effectiveness, safety and cost benefits of splints on DRFs in children.

Conclusion:

The conclusion of this study will provide evidence to effectiveness, safety and cost benefits of splints on DRFs in children, which can further guide the selection of appropriate interventions.

PROSPERO registration number:

CRD42019123429
Outcome of postoperative radiation therapy for cholangiocarcinoma and analysis of dose-volume histogram of remnant liver
Authors: Mukai Yuki , Matsuyama Ryusei , Koike Izumi , Kumamoto Takafumi , Kaizu Hisashi , Homma Yuki , Takano Shoko , Sawada Yu , Sugiura Madoka , Yabushita Yasuhiro , Ito Eiko , Sato Mizuki , Endo Itaru , Hata Masaharu
Published: August 2019

The aim of this study was to analyze dose-volume histogram (DVH) of the remnant liver for postoperative cholangiocarcinoma (CCA) patients, to find toxicity rates, and to confirm efficacy of postoperative radiation therapy (RT).

Thirty-two postoperative CCA patients received partial liver resection and postoperative RT with curative intent. The “liver reduction rate” was calculated by contouring liver volume at computed tomography (CT) just before the surgery and at CT for planning the RT. To evaluate late toxicity, the radiation-induced hepatic toxicity (RIHT) was determined by the common terminology criteria for adverse events toxicity grade of bilirubin, aspartate transaminase, alanine transaminase, alkaline phosphatase, and albumin, and was defined from 3 months after RT until liver metastasis was revealed. The radiation-induced liver disease (RILD) was also evaluated.

Tumor stages were distributed as follows: I: 1, II: 8, IIIA: 1, IIIB: 6, IIIC: 14, IVA: 2. Median prescribed total dose was 50 Gy. Median follow-up time was 27 months. Two-year overall survival (OS): 72.4%, disease-free survival: 47.7%, local control: 65.3%, and the median survival time was 40 months. The median “liver reduction rate” was 21%. The OS had statistically significant difference in nodal status (P = .032) and “liver reduction rate” >30% (P = .016). In the association between the ≥grade 2 RIHT and DVH, there were significantly differences in V30 and V40 (P = .041, P = .034), respectively. The grade ≥2 RIHT rates differ also significantly by sex (P = .008). Two patients (6.2%) were suspected of RILD.

We suggest that RT for remnant liver should be considered the liver V30, V40 to prevent radiation-induced liver dysfunction.
Traditional Chinese medicine (Xiaoai Jiedu Decoction) as an adjuvant treatment for prevention new colorectal adenomatous polyp occurrence in post-polypectomy
Authors: Zhou Qing , Chen Yu-Gen , Xiao Jun , Chen Ting-ting , Liu Jian-rong , Zhou Wan , Li Wei-zhong , Wang Yan , Zhang Bei-ping , lin Jiang , Meng Fan-dong , Gong Biao , Zheng Guo-ying , Han Shu-tang , Cheng Hai-bo
Published: August 2019

Background:

Colorectal Adenomatous Polyp (CAP) was one precursor of colorectal cancer (CRC) and having a high chance of developing into CRC. There was a lack of conclusive chemoprevention evidences to prevention new CAP occurrence in post-polypectomy. Xiaoai Jiedu Decoction, Chinese National Medical Professor (Zhou Zhongying)'s experience formula, has been used to treat new CAP occurrence in post-polypectomy from the 20th century in China. However, clinical research of Xiaoai Jiedu Decoction in the treatment of CAP recurrence was lack. We design this study to evaluate the efficacy and safety of Xiaoai Jiedu Decoction in the treatment of new CAP occurrence in post-polypectomy on colonoscopy.

Methods/Design:

A randomized, controlled, blind and multicenter trial to evaluate the efficacy and safety of Xiaoai Jiedu Decoction is proposed. CAP patients (after complete polypectomy under colonoscopy) will be randomly assigned into Xiaoai Jiedu Decoction group and Xiaoai Jiedu Decoction mimetic agent group. Patients will receive 6-course treatments and a 2-year follow-up. Follow-up colonoscopy will be anticipated to perform in 1 and 2 years after the baseline examinations. The primary outcome measure is the new CAP occurrence in 1 and 2 years. The secondary outcome measure is the occurrence of advanced adenoma in 1 and 2 years.

Discussion:

This study will provide objective evidences to evaluate the efficacy and safety of Xiaoai Jiedu Decoction as an adjuvant treatment for new CAP occurrence in post-polypectomy.

Trial registration:

NCT03616444.
Status and associated characteristics of HIV disclosure among people living with HIV/AIDS in Liangshan, China
Authors: Yin Yao , Yang Hui , Xie Xia , Wang Huan , Nie Anliu , Chen Hong
Published: August 2019

Human immunodeficiency virus (HIV) disclosure is a prerequisite to get access to antiretroviral therapy (ART) and social support. Increased disclosure of HIV status has been shown to reduce mother-to-child transmission and high-risk sexual behaviors. Limited studies were conducted to get an insight into HIV disclosure among people living with HIV/acquired immune deficiency syndrome (AIDS) (PLWHA) in Liangshan.

Our study aimed to investigate the status and associated characteristics of HIV disclosure among PLWHA in Liangshan.

We conducted a cross-sectional study using a stratified, convenience sampling method from August to December in 2017. All of the participants were from Liangshan, a typical impoverished mountainous area which also has a long history of drug production and drug trade. Each participant completed a structured questionnaire including HIV disclosure status, demographic and HIV-related characteristics, social support, and perceived HIV-related stigma. We performed a binary regression analysis to detect associated characteristics of HIV disclosure among PLWHA in Liangshan.

A final sample size of 318 participants was included in this study. The overall prevalence of HIV disclosure was 83.6% (266/318). In binary logistic regression analysis, PLWHA who had higher educational levels, and got infected by sexual transmission were less likely to disclose their HIV status (both P < .05). HIV nondisclosure was correlated with a higher level of perceived HIV-related stigma (P < .01).

The prevalence of HIV disclosure was relatively low in Liangshan. Healthcare workers are suggested to conduct more counseling and education to promote safe sexual behaviors and reduce perceived stigma among PLWHA, then enhance HIV serostatus disclosure.
Frequency, incidence and survival outcomes of clear cell renal cell carcinoma in the United States from 1973 to 2014
Authors: Feng Xiao , Zhang Lina , Tu Wenzhi , Cang Shundong
Published: August 2019

The epidemiological and prognostic data focusing on clear cell renal cell carcinoma (ccRCC) are rarely presented. This study was aimed to define the frequency, incidence, and survival outcomes of ccRCC in the United States.

The Surveillance, Epidemiology, and End Results (SEER) database was searched for patients with ccRCC from 1973 to 2014. Two patient cohorts were utilized: patient cohorts of SEER 18 registries and 9 registries. Overall survival was determined with Kaplan–Meier method and compared across groups with log-rank test.

The incidence rate of ccRCC increased with advancing age, peaked in individuals aged 60 to 79 years, and declined in individuals aged ≥80 years. The incidence rate of ccRCC was significantly higher in males than females (1.94: 1, P < .0001), in Whites than Blacks or others (1:0.79:0.91, P < .0001). The incidence rate of ccRCC with right side as primary origin was slightly but significantly higher than that with left side as primary origin (1:0.96, P = .0006). The incidence rate of ccRCC in Grade II was higher than other grades. Generally, the incidence rates of ccRCC in most circumstances started to surge in the middle 1990s. Survival outcomes of ccRCC worsened with advancing age at diagnosis, tumor grade, and stage. A better prognosis was observed in females than males, in Whites than Blacks, and in individuals diagnosed in 2006 to 2014 than 1973 to 2005.

To the best of our knowledge, the present study firstly presented long-term and updated epidemiological and prognostic data concerning ccRCC in the United States. Significant differences in incidence rates and survival outcomes stratified by different variables were identified.
Beneficial effect of consolidative radiotherapy for patients with lymphoma and skeletal involvement
Authors: Xiao Yin , Zhu Fang , Liu Tao , Li Qiuhui , Li Xiaoqian , Wu Gang , Li Juan , Zhang Liling
Published: August 2019

The objectives of this study were to analyze the clinical features of patients with bone involved lymphoma and identify the prognostic factors and to explore the optimized treatment strategy for bone involved lymphoma.

A total of 1948 patients with lymphoma in our cancer center from September 2006 to October 2017 were retrospectively evaluated. Among these, 109 patients with skeletal involvement in lymphoma were enrolled. According to the pathologic subtypes, the patients were divided into 3 subgroups: classic Hodgkin lymphoma (cHL), B-cell non-Hodgkin lymphoma (B-NHL), and T-cell non-Hodgkin lymphoma (T-NHL). The clinical characteristics and overall survival (OS) of 3 groups of patients were reviewed, and the prognostic factors were analyzed.

There were 9 (3 unifocal, 6 multifocal) patients with primary bone lymphoma. The 5-year OS of cHL, B-NHL, and T-NHL patients was 88.24%, 54.09%, and 61.58%, respectively. Advanced stage, elevated lactate dehydrogenase (LDH), age above 60, high International Prognostic Index score, and treatment without radiotherapy for the bone involved were significant poor prognostic factors for OS of all patients in univariate analysis. There was a trend toward better OS not only in limited-stage but also in advanced-stage patients with radiotherapy for the bone involved compared with the patients without radiotherapy. Elevated LDH level and age above 60 were the independent unfavorable prognostic factor in multivariate analysis.

Elevated LDH level and age above 60 predict the poor prognosis of patients with bone involvement. The potential for long-term survival suggests that additional consolidative radiotherapy for the site of skeleton involvement may have a better chance of long-term success.
Pulmonary Computed Tomography Parenchymal and Vascular Features Diagnostic of Postablation Pulmonary Vein Stenosis
Authors: Goitein Orly , Konen Eli , Lieberman Sivan , Marom Edith M. , Brodov Yafim , Bekker Elena , Beinart Roy , Di Segni Elio , Glikson Michael , Davidson Tima
Published: August 2019

Purpose:

The purpose of this study was to define the full spectrum of pulmonary computed tomography (CT) changes characteristic of postablation pulmonary vein stenosis (PVS).

Materials and Methods:

We retrospectively reviewed our pulmonary vein isolation database. PVS was graded as follows: grade 1:<50%, grade 2: 50% to 75%, grade 3: 76% to 99%, and grade 4: total occlusion. CT parenchymal and vascular changes were detected and correlated with clinical course and nuclear scans.

Results:

Of 486 patients who underwent pulmonary vein isolation, 56 patients (11%) were symptomatic, prompting referral to CT evaluation. Grades 1, 2, 3, and 4 PVS were documented in 42, 1, 2, and 11 patients, respectively. Apart from PVS, abnormal CT findings were present only in patients with PVS grades 2 to 4. Pulmonary parenchymal changes (consolidation, “ground glass” opacities, interlobular septal thickening, and volume loss) were found in PVS grades 2 to 4. Pulmonary vascular changes (oligemia, “sluggish flow,” and collateral mediastinal vessels) were shown in patients with grades 3 to 4 PVS. Concomitant nuclear scans documented reduced lung perfusion. All findings were located to the lobe drained by the affected vein. Complete resolution of pulmonary findings on follow-up CT scans was demonstrated in 20% of patients. Eleven stents were inserted in 7 patients with PVS grades 2 to 4, none of which demonstrated radiologic or clinical resolution.

Conclusions:

A typical CT complex of both parenchymal and vascular findings in the affected lobe is diagnostic of postablation PVS. Lack of clinical and radiologic resolution in most patients, even after stent insertion, further highlights the importance of early recognition of this underdiagnosed condition.
Circulating MicroRNAs in Small-bowel Neuroendocrine Tumors
Authors: Malczewska Anna , Frampton Adam E. , Mato Prado Mireia , Ameri Shima , Dabrowska Aleksandra F. , Zagorac Sladjana , Clift Ashley K. , Kos-Kudła Beata , Faiz Omar , Stebbing Justin , Castellano Leandro , Frilling Andrea
Published: August 2019

Objective:

To discover serum-based microRNA (miRNA) biomarkers for small-bowel neuroendocrine tumors (SBNET) to help guide clinical decisions.

Background:

MiRNAs are small noncoding RNA molecules implicated in the initiation and progression of many cancers. MiRNAs are remarkably stable in bodily fluids, and can potentially be translated into clinically useful biomarkers. Novel biomarkers are needed in SBNET to determine disease aggressiveness, select patients for treatment, detect early recurrence, and monitor response.

Methods:

This study was performed in 3 stages (discovery, validation, and a prospective, longitudinal assessment). Discovery comprised of global profiling of 376 miRNA in sera from SBNET patients (n = 11) versus healthy controls (HCs; n = 3). Up-regulated miRNAs were subsequently validated in additional SBNET (n = 33) and HC sera (n = 14); and then longitudinally after SBNET resection (n = 12), with serial serum sampling (preoperatively day 0; postoperatively at 1 week, 1 month, and 12 months).

Results:

Four serum miRNAs (miR-125b-5p, -362–5p, -425–5p and -500a-5p) were significantly up-regulated in SBNET (P < 0.05; fold-change >2) based on multiple normalization strategies, and were validated by RT-qPCR. This combination was able to differentiate SBNET from HC with an area under the curve of 0.951. Longitudinal assessment revealed that miR-125b-5p returned towards HC levels at 1 month postoperatively in patients without disease, whereas remaining up-regulated in those with residual disease (RSD). This was also true at 12 months postoperatively. In addition, miR-362–5p appeared up-regulated at 12 months in RSD and recurrent disease (RCD).

Conclusions:

Our study represents the largest global profiling of serum miRNAs in SBNET patients, and the first to evaluate ongoing serum miRNA expression changes after surgical resection. Serum miR-125b-5p and miR-362–5p have potential to be used to detect RSD/RCD.