bluuebunny/crossref_metadata_2025 huggingface dataset:
Innovation by Computer-Aided Design/Computer-Aided Manufacturing Technology: A Look at Infection Prevention in Dental Settings
Authors: Barenghi Livia , Barenghi Alberto , Cadeo Carlo , Di Blasio Alberto
Published: August 2019

Recent data indicates limited awareness and compliance on infection prevention procedures by dental offices and by dental laboratories. Guidelines for infection prevention in dentistry have been published by Centres for Disease Control and Prevention since 2003; the section “IX-Special consideration” includes a subsection concerning the prevention in dental laboratories, but it has not been modernised in later versions to fit the needs of traditional and computer-aided technology. Traditional techniques required disinfecting items (impression, chewing waxes, and appliances) with well-suited products, which are also chosen for limiting impression changes or appliance deterioration. Effective procedures are available with difficulties. Some of these contain irritant or non-eco-friendly disinfectants. The transport of impression, to dental laboratories, is often delayed with limited precautions for limiting cross-infection. Gypsum casts are frequently contaminated mainly by bacteria and their antibiotic-resistant strains and even stored for long periods during dental implant supported restoration and orthodontic therapy, becoming a hidden source of infection. Nowadays, computer-aided design/computer-aided manufacturing technology seems to be an interesting way to promote both business and safety, being more comfortable for patients and more accurate than traditional technology. A further advantage is easier infection prevention since, for the most part, mainly digital impression and casts are not a source of cross-infection and the transport of contaminated items is reduced and limited to try-in stages. Nevertheless, a peculiar feature is that a digital electronic file is of course unalterable, but may be ruined by a computer virus. Additionally, the reconditioning of scanner tips is determinant for the optical characteristics and long term use of the scanner, but information for its reconditioning from producers is often limited. This study focuses on some critical points including (a) insufficient guidelines, (b) choice of proper procedure for scanner reconditioning, and (c) data protection in relation to patient privacy.
Ultra-Wideband Dielectric Lens Antennas for Beamsteering Systems
Authors: dos Santos Renan Alves , Lobão da Silva Fré Gabriel , da Silva Luís Gustavo , Paiva Marcelo Carneiro de , Spadoti Danilo Henrique
Published: August 2019

This paper presents a high-directivity ultra-wideband beamsteering antenna array. An innovative beamsteering system based on hemispherical dielectric lenses fed by a set of different printed antennas is proposed. Diversity of signals in different spatial positions can be radiated at the same time. A prototype was manufactured and characterized, operating in a bandwidth varying from 8 GHz to 12 GHz with gain up to 13 dBi.
Decomposition‐Based Multiobjective Optimization with Invasive Weed Colonies
Authors: Tan Yanyan , Lu Xue , Liu Yan , Wang Qiang , Zhang Huaxiang
Published: August 2019

In order to solve the multiobjective optimization problems efficiently, this paper presents a hybrid multiobjective optimization algorithm which originates from invasive weed optimization (IWO) and multiobjective evolutionary algorithm based on decomposition (MOEA/D), a popular framework for multiobjective optimization. IWO is a simple but powerful numerical stochastic optimization method inspired from colonizing weeds; it is very robust and well adapted to changes in the environment. Based on the smart and distinct features of IWO and MOEA/D, we introduce multiobjective invasive weed optimization algorithm based on decomposition, abbreviated as MOEA/D‐IWO, and try to combine their excellent features in this hybrid algorithm. The efficiency of the algorithm both in convergence speed and optimality of results are compared with MOEA/D and some other popular multiobjective optimization algorithms through a big set of experiments on benchmark functions. Experimental results show the competitive performance of MOEA/D‐IWO in solving these complicated multiobjective optimization problems.
New Bioactive Metabolites from the Thermophilic FungusPenicilliumsp. Isolated from Ghamiqa Hot Spring in Saudi Arabia
Authors: Orfali Raha , Perveen Shagufta
Published: August 2019

The thermophilic fungusPenicilliumspecies was isolated from Ghamiqa hot spring sediments in Saudi Arabia. Extract ofPenicilliumspecies cultured on solid rice medium yielded two new compounds 3-(furan 12-carboxylic acid)-6-(methoxycarbonyl)-4-hydroxy-4-methyl-4 and 5-dihydro-2H-pyran13α-methyl-7-hydroxy-5-carboxylic acid methyl ester-1-indanone2. In addition, three known compounds, austinol3, emodin4, and 2-methyl-penicinoline5, were isolated. The structures of the new compounds were unambiguously determined by comprehensive analysis of spectroscopic data, one- and two-dimensional NMR spectroscopy, and high-resolution mass spectrometry. All isolated metabolites were studied for their antibiotic effect against several pathogenic bacteria and for their cytotoxicity against the lymphoma human cancer cell line HTB-176. Austinol3exhibited strong antibacterial activity againstP. aeruginosabacterial strain with an MIC value of 0.13 ± 0.4 µg·mL−1, whereas emodin4demonstrated significant cytotoxicity against the tested HTB-176 cell line with an IC50value of 2 ± 7.6 µM, while the other compounds were moderate to inactive with IC50ranging from 4.3 ± 0.25–22 ± 2.94 µM in this assay.
The Association between rs2292239 Polymorphism in ERBB3 Gene and Type 1 Diabetes: A Meta-Analysis
Authors: Wang Dingjian , Pan Guixia
Published: August 2019

Objectives. The purpose of this study was to explore the association between rs2292239 polymorphism in ERBB3 gene and type 1 diabetes (T1D). Methods. A systematic search of studies on the association of rs2292239 polymorphism in ERBB3 gene with T1D susceptibility was conducted in PubMed, Web of science, Elsevier Science Direct, and Cochrane Library. Eventually, 9 published studies were included. The strength of association between rs2292239 polymorphism and T1D susceptibility was assessed by odds ratios (ORs) with its 95% confidence intervals (CIs). Results. A total of 9 case-control studies, consisting of 5369 T1D patients and 6920 controls, were included in the meta-analysis. This meta-analysis showed significant association between ERBB3 rs2292239 polymorphism and T1D susceptibility in overall population (A vs. C, OR: 1.292, 95% CI= 1.224-1.364, PH=0.450, PH is P value for the heterogeneity test). Similar results were found in subgroup analysis by ethnicity. Conclusions. ERBB3 rs2292239 polymorphism is associated with T1D susceptibility and rs2292239-A allele is a risk factor for T1D. However, more large-scale studies are warranted to replicate our findings.
Monocyte Subsets, Stanford-A Acute Aortic Dissection, and Carotid Artery Stenosis: New Evidences
Authors: Cifani Noemi , Proietta Maria , Taurino Maurizio , Tritapepe Luigi , Del Porto Flavia
Published: August 2019

Monocytes are a heterogeneous cell population distinguished into three subsets with distinctive phenotypic and functional properties: “classical” (CD14++CD16-), “intermediate” (CD14++CD16+), and “nonclassical” (CD14+CD16++). Monocyte subsets play a pivotal role in many inflammatory systemic diseases including atherosclerosis (ATS). Only a low number of studies evaluated monocyte behavior in patients affected by cardiovascular diseases, and data about their role in acute aortic dissection (AAD) are lacking. Thus, the aim of this study was to investigate CD14++CD16-, CD14++CD16+, and CD14+CD16++ cells in patients with Stanford-A AAD and in patients with carotid artery stenosis (CAS).Methods. 20 patients with carotid artery stenosis (CAS group), 17 patients with Stanford-A AAD (AAD group), and 17 subjects with traditional cardiovascular risk factors (RF group) were enrolled. Monocyte subset frequency was determined by flow cytometry.Results. Classical monocytes were significantly increased in the AAD group versus CAS and RF groups, whereas intermediate monocytes were significantly decreased in the AAD group versus CAS and RF groups.Conclusions. Results of this study identify in AAD patients a peculiar monocyte array that can partly explain depletion of T CD4+ lymphocyte subpopulations observed in patients affected by AAD.
The Goldilocks Window of Personalized Chemotherapy: Getting the Immune Response Just Right
Authors: Park Derek S. , Robertson-Tessi Mark , Luddy Kimberly A. , Maini Philip K. , Bonsall Michael B. , Gatenby Robert A. , Anderson Alexander R.A.
Published: August 2019

The immune system is a robust and often untapped accomplice of many standard cancer therapies. A majority of tumors exist in a state of immune tolerance where the patient's immune system has become insensitive to the cancer cells. Because of its lymphodepleting effects, chemotherapy has the potential to break this tolerance. To investigate this, we created a mathematical modeling framework of tumor-immune dynamics. Our results suggest that optimal chemotherapy scheduling must balance two opposing objectives: maximizing tumor reduction while preserving patient immune function. Successful treatment requires therapy to operate in a “Goldilocks Window” where patient immune health is not overly compromised. By keeping therapy “just right,” we show that the synergistic effects of immune activation and chemotherapy can maximize tumor reduction and control.

Significance:

To maximize the synergy between chemotherapy and antitumor immune response, lymphodepleting therapy must be balanced in a “Goldilocks Window” of optimal dosing.
Mapping and Making Sense of Noncoding Mutations in the Genome
Authors: Yang Jiekun , Adli Mazhar
Published: August 2019

Whole-genome sequencing efforts of tumors and normal tissues have identified numerous genetic mutations, both somatic and germline, that do not overlap with coding genomic sequences. Attributing a functional role to these noncoding mutations and characterizing them using experimental methods has been more challenging compared with coding mutations. In this review, we provide a brief introduction to the world of noncoding mutations. We discuss recent progress in identifying noncoding mutations and the analytic and experimental approaches utilized to interpret their functional roles. We also highlight the potential mechanisms by which a noncoding mutation may exert its effect and discuss future challenges and opportunities.
Prediagnostic Level of Dietary and Urinary Isoflavonoids in Relation to Risk of Liver Cancer in Shanghai, China
Authors: Zhang Wei , Wang Jing , Gao Jing , Li Hong-Lan , Han Li-Hua , Lan Qing , Rothman Nathaniel , Zheng Wei , Shu Xiao-Ou , Xiang Yong-Bing
Published: August 2019

Background:

No epidemiologic studies have directly assessed the association between dietary and urinary isoflavonoids and risk of liver cancer in humans.

Methods:

A nested case–control study, including 217 incident cases of liver cancer and 427 individually matched control subjects, was conducted in Shanghai, China. Dietary isoflavonoid intakes were assessed through a validated food-frequency questionnaire and the Chinese Food Composition Tables. Urinary excretion levels of four major isoflavonoids were measured by the reversed-phase high-performance liquid chromatography. ORs and 95% confidence intervals (CI) were derived using conditional logistic regression models.

Results:

The adjusted ORs (95% CIs) for liver cancer across increasing quartiles of urinary genistein levels were 1.00 (reference), 0.55 (95% CI, 0.22–1.36), 0.57 (95% CI, 0.23–1.43), and 0.19 (95% CI, 0.06–0.59) (Ptrend = 0.008) in women and 1.00 (reference), 1.22 (0.52–2.86), 1.17(0.47–2.90), and 1.23 (0.55–2.76) in men, respectively. These associations were consistent by limiting the cases to primary malignant neoplasm of liver or malignant neoplasms of the intrahepatic bile ducts, or among participants without self-reported liver disease or cirrhosis at the baseline survey. No associations were found between dietary isoflavonoids and liver cancer risk.

Conclusions:

Our study suggests for the first time that urinary excretion of genistein may be associated with reduced risk of liver cancer in women.

Impact:

In this nested case–control study in China, we found that urinary excretion of genistein was associated with lower risk of liver cancer in women, and not in men.
Statin Use and Prostate Cancer Incidence in Manitoba, Canada: A Population-Based Nested Case–Control Study
Authors: Righolt Christiaan H. , Bisewski Robert , Mahmud Salaheddin M.
Published: August 2019

Background:

A link between statin use and prostate cancer risk has been proposed. Epidemiologic evidence is, however, inconclusive, and data for specific statin types as well as for period, duration, and dose of use are lacking.

Methods:

We conducted a population-based nested case– control study using administrative data in Manitoba, Canada. Prostate cancer cases were matched to cancer-free controls, and their statin use (including period, duration, and dose of use) was assessed (with adjustment for prostate cancer screening) for statins as a class and for each specific statin.

Results:

We matched 9,384 prostate cancer cases to 46,749 cancer-free controls. Ever use of any statin was not associated with prostate cancer risk, odds ratio (OR) 0.96 (95% confidence interval, 0.90–1.03). Except for pravastatin, 0.82 (0.71–0.96), individual statins were not associated with prostate cancer risk. There was no dose or duration response for pravastatin (or any other statin).

Conclusions:

We found limited evidence of an association between statin use and prostate cancer risk. The association between pravastatin and prostate cancer risk may be due to chance.

Impact:

We show that statin use is not associated with prostate cancer risk after adjustment for screening for a large population with data going back to the mid-1990s.
Exposure to Polybrominated Diphenyl Ethers and a Polybrominated Biphenyl and Risk of Thyroid Cancer in Women: Single and Multi-Pollutant Approaches
Authors: Deziel Nicole C. , Alfonso-Garrido Javier , Warren Joshua L. , Huang Huang , Sjodin Andreas , Zhang Yawei
Published: August 2019

Background:

Thyroid cancer incidence is the most rapidly increasing malignancy; rates are three times higher in women than men. Thyroid hormone–disrupting flame-retardant chemicals, including polybrominated diphenyl ethers (PBDE) and polybrominated biphenyls (PBB), may contribute to this trend.

Methods:

We investigated the relationship between PBDE/PBB exposure and papillary thyroid cancer (PTC) in 250 incident female papillary thyroid cancer cases and 250 female controls frequency-matched on age. Interviews and postdiagnostic serum samples were collected from 2010 to 2013. Serum samples were analyzed for 11 congeners. We calculated ORs and 95% confidence intervals (95% CI) using single-pollutant logistic regression models for continuous and categorical lipid-adjusted serum concentrations of PBDE/PBB, adjusted for age, alcohol consumption, and education. We applied three multi-pollutant approaches [standard multipollutant regression models, hierarchical Bayesian logistic regression modeling (HBLR), principal components analysis (PCA)] to investigate associations with PBDE/PBB mixtures.

Results:

In single-pollutant models, a decreased risk was observed at the highest (>90th percentile) versus lowest (<median) category of BDE-209 concentrations (OR, 0.47; 95% CI, 0.23–0.98); an elevated PTC risk was observed at the highest versus lowest category of BB-153 concentrations (OR, 1.81; 95% CI, 0.96–3.39). In standard multi-pollutant models, an interquartile range increase in BDE-100 concentrations was associated with increased PTC risk (OR, 1.18; 95% CI, 1.01–1.38). HBLR and PCA yielded no statistically significant results.

Conclusions:

Our results using single- and multi-pollutant modeling do not generally support a positive association with PBDE/PBB and PTC risk.

Impact:

Prospective studies with more advanced statistical approaches to analyze mixtures and populations with higher exposures could reveal new insights.
Blockade of TIGIT/CD155 Signaling Reverses T-cell Exhaustion and Enhances Antitumor Capability in Head and Neck Squamous Cell Carcinoma
Authors: Wu Lei , Mao Liang , Liu Jian-Feng , Chen Lei , Yu Guang-Tao , Yang Lei-Lei , Wu Hao , Bu Lin-Lin , Kulkarni Ashok B. , Zhang Wen-Feng , Sun Zhi-Jun
Published: August 2019

Immunosuppression is common in head and neck squamous cell carcinoma (HNSCC). In previous studies, the TIGIT/CD155 pathway was identified as an immune-checkpoint signaling pathway that contributes to the “exhaustion” state of infiltrating T cells. Here, we sought to explore the clinical significance of TIGIT/CD155 signaling in HNSCC and identify the therapeutic effect of the TIGIT/CD155 pathway in a transgenic mouse model. TIGIT was overexpressed on tumor-infiltrating CD8+ and CD4+ T cells in both HNSCC patients and mouse models, and was correlated with immune-checkpoint molecules (PD-1, TIM-3, and LAG-3). TIGIT was also expressed on murine regulatory T cells (Treg) and correlated with immune suppression. Using a human HNSCC tissue microarray, we found that CD155 was expressed in tumor and tumor-infiltrating stromal cells, and also indicated poor overall survival. Multispectral IHC indicated that CD155 was coexpressed with CD11b or CD11c in tumor-infiltrating stromal cells. Anti-TIGIT treatment significantly delayed tumor growth in transgenic HNSCC mouse models and enhanced antitumor immune responses by activating CD8+ T-cell effector function and reducing the population of Tregs. In vitro coculture studies showed that anti-TIGIT treatment significantly abrogated the immunosuppressive capacity of myeloid-derived suppressor cells (MDSC), by decreasing Arg1 transcripts, and Tregs, by reducing TGFβ1 secretion. In vivo depletion studies showed that the therapeutic efficacy by anti-TIGIT mainly relies on CD8+ T cells and Tregs. Blocking PD-1/PD-L1 signaling increased the expression of TIGIT on Tregs. These results present a translatable method to improve antitumor immune responses by targeting TIGIT/CD155 signaling in HNSCC.
Assessment of Losartan 50 mg on Survival of Post-Dialysis Euvolemic Hypertensive Patients: Findings from HELD Trial
Authors: Aftab Raja Ahsan , Khan Amer Hayat , Adnan Azreen Syazril , Sulaiman Syed Azhar Syed , Khan Tahir Mehmood
Published: August 2019

Aims and objective: To estimate the effect of losartan 50 mg on survival of post-dialysis euvolemic hypertensive patients. Methodology: A single center, prospective, single-blind randomized trial was conducted to estimate the survival of post-dialysis euvolemic hypertensive patients when treated with lorsartan 50 mg every other day. Post-dialysis euvolemic assessment was done by a body composition monitor. Covariate Adaptive Randomization was used for allocation of participants to the standard or intervention arm, and the follow-up duration was twelve months. The primary end point was achieving targeted blood pressure (BP) of <140/90 mm Hg and maintaining for 4 weeks, whereas secondary end point was all cause of mortality. Pre-, intra-, and post-dialysis session BP measurements were recorded, and survival trends were analyzed using Kaplan-Meier analysis. Results: Of the total 229 patients, 96 (41.9%) were identified as post-dialysis euvolemic hypertensive. Final samples of 88 (40.1%) patients were randomized into standard (n = 44) and intervention arms (n = 44), and 36 (81.8%) patients in each arm completed a follow-up of 12 months. A total of eight patients passed away during the 12-month follow-up period (6 deaths among standard arm and 2 in intervention arm). However, the probability of survival between both arms was not significant (p = 0.13). Cox regression analysis revealed that chances of survival were higher among the patients in the intervention (OR 3.17) arm than the standard arm (OR 0.31); however, the survival was found not statistically significant. Conclusion: There was no statistical significant difference in 1 year survival of post-dialysis euvolemic hypertensive patients when treated with losartan 50 mg.
Outcome Predictors of SD-OCT-Driven Intravitreal Ranibizumab in Choroidal Neovascularization due to Myopia
Authors: Guichard Maria-Magdalena , Peters Géraldine , Tuerksever Cengiz , Pruente Christian , Hatz Katja
Published: August 2019

Purpose: To analyze the efficacy and outcome predictors of SD-OCT (spectral-domain optical coherence tomography)-driven ranibizumab treatment in patients with choroidal neovascularization due to myopia (mCNV). Methods: This prospective investigator-initiated study includes 20 patients with treatment-naïve mCNV. Evaluation included best-corrected visual acuity (BCVA), morphological SD-OCT parameters, and treatment frequency. Results: From baseline to month 12, BCVA improved from 58.5 ± 16.9 to 66.1 ± 14.9 letters. Central retinal thickness (CRT) significantly decreased, and qualitative SD-OCT parameters improved. Better baseline visual acuity (VA), lower spherical equivalent, better inner/outer segment line and external limiting membrane integrity showed a significant positive effect on BCVA outcome. Less fluctuation in CRT (worst minus best CRT) indicated better BCVA at 12 months. No serious adverse events occurred. Conclusions: SD-OCT-guided intravitreal ranibizumab treatment in mCNV was efficient and safe. We determined useful predictive factors in regard to VA outcome after 12 months.
Noninvasive Prediction of Twitch Transdiaphragmatic Pressure: Insights from Spirometry, Diaphragm Ultrasound, and Phrenic Nerve Stimulation Studies
Authors: Spiesshoefer Jens , Henke Carolin , Herkenrath Simon Dominik , Randerath Winfried , Brix Tobias , Görlich Dennis , Young Peter , Boentert Matthias
Published: August 2019

Background: Twitch transdiaphragmatic pressure (twPdi) following magnetic stimulation (MS) of the phrenic nerves is the gold standard for non-volitional assessment of diaphragm strength. Expiratory muscle function can be investigated using MS of the abdominal muscles and measurement of twitch gastric pressure (twPgas). Objectives: To investigate whether twitch pressures following MS of the phrenic and lower thoracic nerve roots can be predicted noninvasively by diaphragm ultrasound parameters and volitional tests of respiratory muscle strength. Methods: Sixty-three healthy subjects underwent standard spirometry, measurement of maximum inspiratory (PImax) and expiratory pressure (PEmax), and diaphragm ultrasound. TwPdi following cervical MS of the phrenic nerve roots and twPgas after lower thoracic MS (twPgas-Thor) were measured using esophageal and gastric balloon catheters inserted transnasally. Using surface electrodes, compound muscle action potentials (CMAP) were simultaneously recorded from the diaphragm or obliquus abdominis muscles, respectively. Results: Forced expiratory flow (FEF25–75) was significantly correlated with twPdi (r = 0.37; p = 0.003) and its components (twPgas and twitch esophageal pressure, twPes). Diaphragm excursion velocity during tidal breathing was correlated to twPes (r = 0.44; p = 0.02). No prediction of twitch pressures was possible from CMAP amplitude, forced vital capacity (FVC), or PImax. TwPgas-Thor was correlated with FEF25–75 (r = 0.46; p = 0.05) and diaphragm thickness at total lung capacity (r = 0.38; p = 0.04) but could not be predicted from CMAP amplitude, FVC, or PEmax. Conclusions: TwPdi and twPgas-Thor cannot be predicted from volitional measures of respiratory muscle strength, diaphragm and abdominal CMAP, or diaphragm ultrasound. Invasive recording of esophageal and gastric pressures following MS remains indispensable for objective assessment of respiratory muscle strength.
Differential Organ-Specific Tumor Response to Immune Checkpoint Inhibitors in Hepatocellular Carcinoma
Authors: Lu Li-Chun , Hsu Chiun , Shao Yu-Yun , Chao Yee , Yen Chia-Jui , Shih I-Lun , Hung Yi-Ping , Chang Chun-Jung , Shen Ying-Chun , Guo Jhe-Cyuan , Liu Tsung-Hao , Hsu Chih-Hung , Cheng Ann-Lii
Published: August 2019

Background and Aims: Immune checkpoint inhibitors (ICIs) exhibit significant clinical activity in patients with advanced hepatocellular carcinoma (HCC). This study explored whether tumor response to ICIs in HCC varies among different organs. Methods: We reviewed the data of patients with advanced HCC who had received ICIs. Patients with measurable diseases were enrolled. Organ-specific response criteria, adapted from RECIST 1.1 and immune-related RECIST, were used to evaluate the objective response to ICIs in tumors located in the liver, lung, lymph node, and other intra-abdominal sites. Results: Of the 75 enrolled patients with advanced HCC, 51 and 11 patients had chronic hepatitis B virus and chronic hepatitis C virus infection, respectively. Regarding ICI treatment, 58, 1, and 16 patients had undergone anti-PD-1/anti-PD-L1 monoclonal antibody (mAb) alone, anti-CTLA4 mAb alone, and anti-PD-1 mAb plus anti-CTLA4 mAb, respectively; 20 and 55 patients had received ICIs as first-line or ≥second-line therapy. The overall objective response rate (ORR) was 28.0%. In total, 58, 34, 19, and 18 patients had measurable hepatic tumors and lung, lymph node, and other intra-abdominal metastases, and the corresponding organ-specific ORRs were 22.4, 41.2, 26.3, and 38.9%, respectively. Of the 39 patients who had both hepatic and extrahepatic tumors, 12 had disease control in extrahepatic tumors while progressive disease (PD) in hepatic tumors, whereas only 4 exhibited disease control in hepatic tumors while PD in extrahepatic tumors (p = 0.046, McNemar test). Of the 16 patients with only evaluable tumors in the liver and lungs at baseline, 8 had disease control in the lungs while PD in the liver, and none experienced disease control in the liver while PD in the lungs (p = 0.005). Conclusions: The hepatic tumors of HCC may be less responsive to ICIs than extrahepatic lesions. Lung metastases responded most favorably to ICIs. The mechanisms underlying this differential response to ICIs warrant further investigation.
Clinical and Pharmacological Aspects of Hospital-Acquired Acute Kidney Injuries Outside the Intensive Care Unit: A Phenome-Wide Association Study
Authors: Nevoret Camille , Jannot Anne-Sophie , Pallet Nicolas
Published: August 2019

Introduction: Acute kidney injury (AKI) occurring in the hospital in noncritically ill patients involves a broad spectrum of clinical conditions and medical scenarios that are better appreciated by systematic association studies. Methods: We extracted all diagnoses and drug prescriptions from an i2b2 clinical data warehouse for patients who stayed in an academic hospital between 2013 and 2017, and had at least two plasma creatinine measurements performed during the first week of their stay, and analyzed the association between AKI occurring outside the intensive care unit (ICU), as identified using the AKIN classification criteria, and International Classification of Diseases (ICD)-10 diagnosis codes and drug categories. Results:16,662 hospital stays for unique individuals were extracted. The prevalence of AKI outside the ICU was 8%, with a distribution of frequencies that greatly varied according to the departments. 4% of patients with AKI died during their hospital stay (OR 6.17, 95% CI [2.59–17.9]). ICD-10 diagnosis codes were related to infections, kidney cancer, heart failure, respiratory failure, and chronic kidney disease. Drugs targeting the renin angiotensin system and loop diuretics had the larger size effect on AKI. The ICD-10 code N17/“Acute kidney failure” was recorded in average in only 16% of the cases with AKI, and its frequency ranged from 0 to 80%, according to the hospital department; the lack of encoding did not impact mortality. Conclusion: A systematic search for the associations of AKI with prescribed drugs and medical diagnosis using a phenome-wide approach allows to describe in depth the epidemiology of AKI outside the ICU.
The Clinicopathological Characteristics of Henoch-Schönlein Purpura Nephritis with Presentation of Nephrotic Syndrome
Authors: Tan Jiaxing , Tang Yi , Xu Yicong , Yan Siyu , Xu Yuanyuan , Tan Li , Zhong Zhengxia , Tarun Padamata , Qin Wei
Published: August 2019

Background: Henoch-Schönlein purpura nephritis (HSPN) is a common vasculitis involving the kidneys, with a lower incidence in adults. Meanwhile, nephrotic syndrome (NS) can appear in HSPN. However, the clinicopathological features and renal outcome of adult-onset HSPN presenting with NS (NS-HSPN) have not been well clarified. Methods: A total of 191 HSPN patients were prospectively analyzed and comparisons were made between NS-HSPN and non-NS-HSPN. Multivariate Cox regression analysis was carried out to find the unfavorable factors of renal outcome of NS-HSPN. Results: Among the 191 patients, 44 (23.0%) had NS-HSPN. Apart from edema and abdominal pain, patients with NS-HSPN tended to have lower levels of erythrocytes and hemoglobulin in blood as well as a greater number of erythrocytes in urine (p < 0.05). Mesangial proliferation was the most common pathological lesion in HSPN and the rates of crescent formation were significantly different, with 54.5% in NS-HSPN and 33.3% in non-NS-HSPN (p < 0.05). Notably, 18.2 and 4.8% of patients reached the composite endpoints in the NS-HSPN and non-NS-HSPN groups, respectively (p < 0.05), demonstrating that NS-HSPN patients were more likely to progress to end-stage renal disease and had a worse outcome. We also found that hypertension, estimated glomerular filtration rate (eGFR), cystatin, and tubular atrophy/interstitial fibrosis (HR > 1, p < 0.05) at onset were correlated with adverse outcome in NS-HSPN. Conclusion: NS-HSPN had more severe clinicopathological manifestations and poorer prognosis. The adverse predictors of NS-HSPN principally depend on clinicopathological presentation rather than on different therapies, and hypertension, eGFR, cystatin, and tubular atrophy/interstitial fibrosis can serve as independent risk factors in NS-HSPN.
Hyaluronic Acid as an Alternative to Autologous Human Serum Eye Drops: Initial Clinical Results with High-Molecular-Weight Hyaluronic Acid Eye Drops
Authors: Beck Ria , Stachs Oliver , Koschmieder Anita , Mueller-Lierheim Wolfgang G.K. , Peschel Sabine , van Setten Gysbert-Botho
Published: August 2019

Introduction: Autologous serum eye drops (ASED) are used in the treatment of most severe stages of dry eye. Once introduced, it is currently considered impossible to return to other lubricating eye drops or other commercially available therapeutic regimen. Materials and Methods: In a randomized study, non-preserved high-molecular-weight hyaluronic acid eye drops were offered as an alternative to 11 patients using autologous serum treatment for at least 3 months. The control group (n = 5) continued their treatment with ASED. The verum group (n = 6) used very-high-molecular-weight hyaluronic eye drops (Comfort Shield®) instead of the ASED. Results: From four of initially six patients in the verum group that finished the study, 2 (50%) preferred to stay with the very-high-molecular-weight hyaluronic acid eye drops beyond the trial period, the other two returned to the earlier therapy with ASED. The control group continued their treatment as before and finished the study after 8 weeks. Conclusion: For the first time, artificial eye drops, i.e., high-molecular-weight hyaluronic acid eye drops, offered an acceptable alternative to ASED. Some patients perceived these drops as even better than the patient’s own serum. This is the first evidence that optimization of the molecular structure of hyaluronic acid can be used to create eye drops that are perceived to be better than other tested tear substitutes and even patients’ own serum. This offers a new treatment perspective for patients with very severe dry eye disease.
Longer Control of Nivolumab in Metastatic Renal Cell Carcinoma Patients with End-Stage Kidney Disease on Dialysis
Authors: Morinaga Ryota , Kawahara Takashi , Miyoshi Yasuhide , Yao Masahiro , Uemura Hiroji
Published: August 2019

Introduction: Nivolumab has been introduced for metastatic renal cell carcinoma (mRCC) as a second-line therapy for years. However, despite widespread evidence of its utility, few reports have described the efficacy of nivolumab for mRCC patients on hemodialysis. Case Presentation: A 68-year-old man with a 20-year history of dialysis due to chronic glomerulotubular nephritis was referred to our department for bilateral renal tumors in 2015. In February 2015, contrast-enhanced CT revealed findings suggestive of RCC, so we performed right nephrectomy. The pathological diagnosis was clear cell carcinoma and papillary renal cell carcinoma. In July 2015, we consequently performed left nephrectomy, and the pathological diagnosis was metastatic RCC. In February 2016, because follow-up CT revealed a right adrenal tumor with time-dependent growth, sunitinib (25 mg/body) was introduced. In January 2017, although sunitinib had controlled the adrenal metastasis for 9 courses (11 months), liver metastasis was observed, so nivolumab was introduced as a second-line chemotherapy in March 2017. Nivolumab was able to control the mRCC for 15 months (32 courses). While CT showed no metastatic sites except for the liver and adrenal glands, his general condition gradually decreased, and he died in October 2018. Conclusion: We herein report a patient with RCC on hemodialysis with long-term cancer control by nivolumab.
Large, Spontaneous Macular Hole with Posterior Pole Detachment in a Patient with Best Vitelliform Macular Dystrophy
Authors: Peart Shamfa , Ramsay Amoy , Khan Qazi Assad , Leong Tony , Gordon-Bennett Patel
Published: August 2019

Purpose: To describe the visual and anatomical outcomes in a patient with a full-thickness macular hole and Best vitelliform macular dystrophy. Methods: The authors present a case of a large spontaneous macular hole with associated posterior pole detachment in a patient with a history of Best vitelliform macular dystrophy including clinical course and surgical outcome. Patient: The patient presented with a history of blurred central vision. He was known to have Best vitelliform macular dystrophy. Examination revealed BCVA 6/36 (0.78 logMAR) and a full-thickness macular hole (1,102 µm) with a shallow posterior pole detachment extending to the vascular arcades. He underwent phacovitrectomy with silicone oil tamponade. Internal limiting membrane (ILM) peel was prohibited due to a very adherent posterior hyaloid membrane (PHM). Results: The patient developed type 2 closure. He had oil removal in 14 months combined with PHM and ILM peel. Two months postoperatively, he had further reduction of the foveal defect and the retina remained flat. Final BCVA was 6/24 (0.60 logMAR). Conclusion: Macular holes with Best disease are rare and are thought to be due to rupture of a cyst in the vitelliform stage or atrophy in later stages. This case outlines that closure of the macular hole, flattening of the detachment, and improvement in visual acuity is possible with vitrectomy and ILM peeling.
Pathophysiology of Alloimmunization
Authors: Molina-Aguilar Rubiraida , Gómez-Ruiz Soledad , Vela-Ojeda Jorge , Montiel-Cervantes Laura Arcelia , Reyes-Maldonado Elba
Published: August 2019

Introduction: Alloimmunization is caused by exposure to erythrocytes from a donor that expresses blood group antigens other than those of the recipient and is related to processes that alter the balance of the immune system. Knowing the pathophysiology of alloimmunization process is essential to understand clinical complications associated with this process. Patients and Methods: From October 2016 to April 2017, irregular antibody screening was performed in 1,434 polytransfused (compatible with the ABO and D system) patients by means of agglutination techniques using erythrocytes of a known phenotype of 44 patients with a positive alloantibody screening. Non-alloimmunized (control) subjects were matched for age, gender, pathology, and treatment group with alloimmunized patients. The subsets of B, T, and Treg lymphocytes were determined by flow cytometry. Results: The results of screening for alloantibodies in patients by specificity of antibodies were as follows: nonspecific (30%), followed by anti-Dia (13%), anti-e (9%), anti-S (9%), anti-I (7%), anti-K (7%), and anti-P (7%). A lower percentage of CD4+ T lymphocytes and an increase of CD8+ T lymphocytes were observed in alloimmunized patients, as well as a low CD4/CD8 ratio (0.7 vs. 1.6, p = 0.003), a higher percentage of B lymphocytes versus the control group (30 vs. 20%, p = 0.003), and a decrease of Treg CD4+ lymphocytes versus the control group (3 vs. 12 cells/μL, p = 0.043). These observations suggest that alloimmunized patients have important alterations in the number of some lymphocyte subsets that can be translated into clinical immune dysregulation. Conclusion: A decreased CD4/CD8 ratio, increased B lymphocytes, and Treg lymphocyte deficiency are the most significant changes observed in alloimmunized patients.
A Case of Double Expresser Diffuse Large B Cell Lymphoma Treated with R-CODOX-M/R-IVAC
Authors: Bemis Thomas , Ioanitescu Jonathan , Mackovick Lynn , Hammad Azzam , Rubin Jascha
Published: August 2019

Diffuse Large B Cell Lymphoma (DLBCL) is a heterogeneous disease with a variety of chromosomal abnormalities contributing to differences in management. While it is known that Double Hit Lymphomas (DHL) warrant more aggressive chemotherapy regimens, debate remains on how to treat Double Expresser Lymphomas (DEL). We present a case of a DEL treated with an aggressive regimen of 2 alternating cycles of R-CODOX-M (rituximab, cyclophosphamide, doxorubicin, vincristine and methotrexate) and R-IVAC (rituximab, ifosfamide, etoposide and high dose cytarabine). The regimen resulted in a significant response to treatment with marked reduction in tumor size and avidity, and an acceptable side effect profile. There was, however, residual metabolic activity on repeat PET CT scan. After consolidation with 36 Grey radiotherapy, a PET CT demonstrated a complete metabolic response. Debate remains regarding treatment approaches in DEL. Our case supports the categorization of DEL alongside DHL as resistant lymphomas requiring a more aggressive regimen than standard therapy.
Particularities and Efficacy of Extracorporeal Shock Wave Lithotripsy in Children
Authors: Brad Alexandru-Bogdan , Ferro Matteo , Vartolomei Mihai-Dorin , Tătaru Sabin , Anton-Păduraru Dana-Teodora , Simion Carmen , Martha Orsolya , Pricop Catalin , Porreca Angelo , Negru Irina
Published: August 2019

Background: Extracorporeal shock wave lithotripsy (ESWL) was first introduced in paediatric population in 1986. Given the more frequent recurrence in children, compared to adults, urinary stones treatments should require minimal invasive treatment methods. In this study, we aimed to evaluate the profile of the young patient with lithiasis who can benefit from ESWL, analysing the experience of 2 clinical departments. Materials and Methods: We have retrospectively reviewed the medical records of 54 children who underwent ESWL for urolithiasis. ESWL success rate was defined as stone-free status or the presence of clinically insignificant residual fragments. Data were analysed using the STATA 14.2. Results: In our study, the incidence of renal-ureteral calculi is significantly higher in girls (68.5%), compared to boys (31.5%). In total, 83.3% of patients showed a favourable outcome after treatment and the remaining 16.7% showed minimal complications. The presence of complications and remaining calculi was correlated to children age. The overall stone free rate was 88.9%. For calculus of 8.5 mm, only one ESWL session is recommended. Conclusions: The high percentage of cases with favourable outcome indicate that ESWL treatment is effective, considering the minimal cost, minimal invasiveness, repeatability and no need for general anaesthesia.
Granulocyte Colony-Stimulating Factor-Producing Bladder Cancer
Authors: Morinaga Ryota , Kawahara Takashi , Kuroda Shinnosuke , Inayama Yoshiaki , Uemura Hiroji
Published: August 2019

Granulocyte colony-stimulating factor (G-CSF)-producing bladder cancer is rare, with only 75 cases reported in Japan. A 67-year-old woman was referred to our institution for the further examination of gross hematuria. Cystoscopy revealed a 7-cm bladder tumor. The initial white blood cell count was 17,100/μL, and a transurethral resected specimen showed G-CSF expression. CT revealed that the tumor had invaded the colon. As the patient had uncontrollable schizophrenia, radical cystectomy was abandoned. We herein report a case of G-CSF-producing bladder tumor.
Molecular Coronary Plaque Imaging Using
18
F-Fluoride
Authors: Moss Alastair J. , Doris Mhairi K. , Andrews Jack P.M. , Bing Rong , Daghem Marwa , van Beek Edwin J. R. , Forsyth Laura , Shah Anoop S.V. , Williams Michelle C. , Sellers Stephanie , Leipsic Jonathon , Dweck Marc R. , Parker Richard A. , Newby David E. , Adamson Philip D.
Published: August 2019

Background:

Coronary
18
F-fluoride positron emission tomography identifies ruptured and high-risk atherosclerotic plaque. The optimal method to identify, to quantify, and to categorize increased coronary
18
F-fluoride uptake and determine its reproducibility has yet to be established. This study aimed to optimize the identification, quantification, categorization, and scan-rescan reproducibility of increased
18
F-fluoride activity in coronary atherosclerotic plaque.

Methods:

In a prospective observational study, patients with multi-vessel coronary artery disease underwent serial
18
F-fluoride positron emission tomography. Coronary
18
F-fluoride activity was visually assessed, quantified, and categorized with reference to maximal tissue to background ratios. Levels of agreement for both visual and quantitative methods were determined between scans and observers.

Results:

Thirty patients (90% male, 20 patients with stable coronary artery disease, and 10 with recent type 1 myocardial infarction) underwent paired serial positron emission tomography-coronary computed tomography angiography imaging within an interval of 12±5 days. A mean of 3.7±1.8
18
F-fluoride positive plaques per patient was identified after recent acute coronary syndrome, compared with 2.4±2.3 positive plaques per patient in stable coronary artery disease. The bias in agreement in maximum tissue to background ratio measurements in visually positive plaques was low between observers (mean difference, −0.01; 95% limits of agreement, −0.32 to 0.30) or between scans (mean difference, 0.06; 95% limits of agreement, −0.49 to 0.61). Good agreement in the categorization of focal
18
F-fluoride uptake was achieved using visual assessment alone (κ=0.66) and further improved at higher maximum tissue to background ratio values.

Conclusions:

Coronary
18
F-fluoride activity is a precise and reproducible metric in the coronary vasculature. The analytical performance of
18
F-fluoride is sufficient to assess the prognostic utility of this radiotracer as a noninvasive imaging biomarker of plaque vulnerability.

Clinical Trial Registration:

URL:
http://www.clinicaltrials.gov
. Unique identifiers: NCT02110303 and NCT02278211.
Smartphone-Based Blood Pressure Measurement Using Transdermal Optical Imaging Technology
Authors: Luo Hong , Yang Deye , Barszczyk Andrew , Vempala Naresh , Wei Jing , Wu Si Jia , Zheng Paul Pu , Fu Genyue , Lee Kang , Feng Zhong-Ping
Published: August 2019

Background:

Cuff-based blood pressure measurement lacks comfort and convenience. Here, we examined whether blood pressure can be determined in a contactless manner using a novel smartphone-based technology called transdermal optical imaging. This technology processes imperceptible facial blood flow changes from videos captured with a smartphone camera and uses advanced machine learning to determine blood pressure from the captured signal.

Methods:

We enrolled 1328 normotensive adults in our study. We used an advanced machine learning algorithm to create computational models that predict reference systolic, diastolic, and pulse pressure from facial blood flow data. We used 70% of our data set to train these models and 15% of our data set to test them. The remaining 15% of the sample was used to validate model performance.

Results:

We found that our models predicted blood pressure with a measurement bias±SD of 0.39±7.30 mm Hg for systolic pressure, −0.20±6.00 mm Hg for diastolic pressure, and 0.52±6.42 mm Hg for pulse pressure, respectively.

Conclusions:

Our results in normotensive adults fall within 5±8 mm Hg of reference measurements. Future work will determine whether these models meet the clinically accepted accuracy threshold of 5±8 mm Hg when tested on a full range of blood pressures according to international accuracy standards.
Lipids, Apolipoproteins, and the Risk of Parkinson Disease
Authors: Fang Fang , Zhan Yiqiang , Hammar Niklas , Shen Xia , Wirdefeldt Karin , Walldius Göran , Mariosa Daniela
Published: August 2019

Rationale:

A complete picture of the associations of the most common lipid fractions, including total cholesterol (TC), LDL-C (low-density lipoprotein cholesterol), HDL-C (high-density lipoprotein cholesterol), triglycerides, and apolipoproteins, with the risk of Parkinson disease (PD), is lacking.

Objective:

To assess the associations of lipids and apolipoproteins with the future risk of PD.

Methods and Results:

In the AMORIS (Apolipoprotein-Related Mortality Risk) Study, we enrolled ≈600 000 participants during 1985 to 1996 in Stockholm, Sweden, with repeated measurements of TC, LDL-C, HDL-C, triglycerides, ApoB (apolipoprotein B), and ApoA-I (apolipoprotein A-I). The cohort was followed until the end of 2011, and incident cases of PD were identified through the Swedish Patient Register. We first used Cox models to estimate the associations of these biomarkers with later risk of PD. We further applied a Mendelian randomization analysis for TC, LDL-C, and triglycerides using the GWAS (Genome-wide association study) summary statistics from the public PD GWAS data and 23andMe PD cohorts with >800 000 individuals. One SD increase of TC was associated with a lower hazard of PD (hazard ratio, 0.90; 95% CI, 0.87–0.94). Similar associations were observed for LDL-C (hazard ratio, 0.93; 95% CI, 0.88–0.98), triglycerides (hazard ratio, 0.94; 95% CI, 0.90–0.97), and ApoB (hazard ratio, 0.91; 95% CI, 0.85–0.97). A clear dose-response relation was also noted when using these biomarkers as categorical variables. A causal inverse association of TC, LDL-C, and triglycerides with PD risk was further suggested by the Mendelian randomization analysis.

Conclusions:

Our findings reinforce that higher levels of TC, LDL-C, and triglycerides are associated with a lower future risk of PD and further suggest that these associations may be causal. The findings for ApoB in relation to PD risk are novel, and whether such association is causal needs to be examined.