bluuebunny/crossref_metadata_2025 huggingface dataset:
Visfatin Induces Inflammation and Insulin Resistance via the NF-κB and STAT3 Signaling Pathways in Hepatocytes
Authors: Heo Yu Jung , Choi Sung-E , Jeon Ja Young , Han Seung Jin , Kim Dae Jung , Kang Yup , Lee Kwan Woo , Kim Hae Jin
Published: July 2019

Background. It has been suggested that visfatin, which is an adipocytokine, exhibits proinflammatory properties and is associated with insulin resistance. Insulin resistance and inflammation are the principal pathogeneses of nonalcoholic fatty liver disease (NAFLD), but the relationship, if any, between visfatin and NAFLD remains unclear. Here, we evaluated the effects of visfatin on hepatic inflammation and insulin resistance in HepG2 cells and examined the molecular mechanisms involved. Methods. After treatment with visfatin, the inflammatory cytokines IL-6, TNF-α, and IL-1β were assessed by real-time polymerase chain reaction (RT-PCR) and immunocytochemical staining in HepG2 cells. To investigate the effects of visfatin on insulin resistance, we evaluated insulin-signaling pathways, such as IR, IRS-1, GSK, and AKT using immunoblotting. We assessed the intracellular signaling molecules including STAT3, NF-κB, IKK, p38, JNK, and ERK by western blotting. We treated HepG2 cells with both visfatin and either AG490 (a JAK2 inhibitor) or Bay 7082 (an NF-κB inhibitor); we examined proinflammatory cytokine mRNA levels using RT-PCR and insulin signaling using western blotting. Results. In HepG2 cells, visfatin significantly increased the levels of proinflammatory cytokines, reduced the levels of proteins (e.g., phospho-IR, phospho-IRS-1 (Tyr612), phospho-AKT, and phospho-GSK-3α/β) involved in insulin signaling, and increased IRS-1 S307 phosphorylation compared to controls. Interestingly, visfatin increased the activities of the JAK2/STAT3 and IKK/NF-κB signaling pathways but not those of the JNK, p38, and ERK pathways. Visfatin-induced inflammation and insulin resistance were regulated by JAK2/STAT3 and IKK/NF-κB signaling; together with AG490 or Bay 7082, visfatin significantly reduced mRNA levels of IL-6, TNF-α and IL-1β and rescued insulin signaling. Conclusion. Visfatin induced proinflammatory cytokine production and inhibited insulin signaling via the STAT3 and NF-κB pathways in HepG2 cells.
Network of Mediators for Vascular Inflammation and Leakage Is Dysbalanced during Cytoreductive Surgery for Late-Stage Ovarian Cancer
Authors: Klaschik Sven , Gehlen Jennifer , Neumann Claudia , Keyver-Paik Mignon-Denise , Soehle Martin , Frede Stilla , Velten Markus , Hoeft Andreas , Hilbert Tobias
Published: July 2019

Background. Cytoreductive surgery (CS) in late-stage ovarian cancer patients is often challenging due to extensive volume shifts, and high fluid intake may provoke postoperative complications. Expression of vasoactive mediators is altered in cancer patients, which may affect systemic vascular function. We sought to assess how serum levels of vasoactive markers and mediators change during CS in ovarian cancer. Methods. Following IRB approval and informed consent, pre- and postoperative serum samples were analyzed in 26 late-stage ovarian cancer patients using multiplex protein arrays and ELISA. Results. The proinflammatory cytokines and chemokines IL-6, IL-8, and CCL2 were significantly elevated after 24 hrs compared to the baseline values, with IL-6 and IL-8 being most prominently increased. While ANGPT1 remained unchanged after surgery, its competitive antagonist ANGPT2 was significantly increased. In contrast, serum levels of the ANGPT receptor TIE2 were decreased to 0.6 of the baseline values. While VEGF-D, E-selectin, P-selectin, ICAM-1, and PECAM-1 remained unchanged, serum activity of both thrombomodulin and syndecan-1 was significantly increased following surgery. Conclusion. We identified a regulatory network of acute-phase reaction during CS in late-stage ovarian cancer. This suggests that IL-6 exerts positive regulation of other proinflammatory mediators and, by upregulating ANGPT2 and suppressing ANGPT1, induces a serum profile that promotes vascular leakage. This may contribute to the observed hemodynamic alterations during CS procedures.
Vergence and Accommodative Dysfunctions in Emmetropic and Myopic Chinese Young Adults
Authors: Ma Martin Ming-Leung , Yeo Anna Chwee Hong , Scheiman Mitchell , Chen Xiang
Published: July 2019

Purpose. To investigate the association between refractive error and common binocular vision and accommodative dysfunctions in Chinese adults and to report the percentage of these disorders in this sample population. Methods. This was a single-site, prospective cross-sectional clinic-based study. A total of 415 Chinese participants aged between 21 and 38 years were grouped into 4 refractive error groups (emmetropia, low, moderate, and high myopia) based on the spherical equivalent power of noncycloplegic refraction. Baseline testing including binocular vision and accommodative testing was performed on all eligible participants. A multiple-sign classification system was used to analyze these data for the diagnosis of common nonstrabismic binocular vision and accommodative dysfunctions. Associations between the diagnosis and refractive error groupings were examined by the chi-square test for the linear trend. Results. Associations with refractive error groupings were found for convergence insufficiency (p=0.008, r = −0.13) and divergence insufficiency (p=0.008, r = 0.131). The 3 most common dysfunctions in this sample population were basic exophoria (10.8%), convergence insufficiency (9.6%), and divergence insufficiency (7.0%). Approximately 40% of the sample population demonstrated at least one type of binocular vision dysfunction. Conclusion. Convergence insufficiency and divergence insufficiency were associated with refractive error groupings. Binocular vision dysfunction was a common finding in this sample population.
Role of Four ABC Transporter Genes in Pharmacogenetic Susceptibility to Breast Cancer in Jordanian Patients
Authors: AL-Eitan Laith N. , Rababa’h Doaa M. , Alghamdi Mansour A. , Khasawneh Rame H.
Published: July 2019

Breast cancer pharmacogenetics is increasingly being explored due to chemotherapy resistance among certain classes of patients. The ATP binding cassette (ABC) transporter genes have been previously implicated in breast cancer progression and drug response. In the present study, single nucleotide polymorphisms (SNPs) from theABCC1,ABCC2,ABCB1, andABCG2genes were screened in breast cancer patients and healthy volunteers from the Jordanian-Arab population. Only theABCB1SNPs showed a significant association with BC in Jordanian-Arab patients, and theABCB1SNP rs2032582 exhibited a strong genotypic association with BC. With regard to the clinical characteristics of BC, theABCC2SNPs rs2273697 and rs717620 were found to be significantly associated with age at breast cancer diagnosis and breastfeeding status, while theABCB1SNP rs1045642 was significantly associated with age at breast cancer diagnosis. In terms of pathological characteristics, theABCC1SNP rs35628 and theABCB1SNP rs2032582 were significantly associated with tumor size, theABCC2SNP rs2273697 was significantly associated with estrogen receptor status, and theABCG2SNP rs2231142 was significantly associated with axillary lymph node status. In this current study, we assume that significant genetic variants within the ABC superfamily may increase the risk of breast cancer among Jordanian women. Furthermore, these variants might be responsible for worse BC prognosis.
Transformation of M/A Constituents during Tempering and Its Effects on Impact Toughness of Weld Metals for X80 Hot Bends
Authors: Qiao Gui-ying , Han Xiu-lin , Chen Xiao-wei , Wang Xu , Liao Bo , Xiao Fu-ren
Published: July 2019

Impact toughness of the weld metal is one of the important factors affecting the quality of hot bends, which is strongly dependent on the microstructure transformation during hot bending and tempering. In this study, three kinds of weld metals with different Ni contents were selected, and then the effects of tempering temperature on the microstructure impact toughness of weld metals for hot bends were investigated by simulation conducted on a Gleeble-3500 thermal simulator. The results show that the nonmetallic inclusion particles in weld metals can become the nuclear core of acicular ferrite like in as-welded metal. So, the overlapping acicular ferrite microstructure is obtained in the weld metal after direct cooling from the reheating temperature. During tempering, the overlapping acicular ferrite microstructure is degenerated, and martensite/austenite (M/A) constituents in the acicular ferrite microstructure decompose into ferrites and carbides. The resulting carbide particles mainly distribute along the acicular ferrite grain boundaries. With the increase of the tempering temperature, the carbide particles coarsen, which decreases the impact toughness of the weld metal of hot bends. Addition of Ni to weld metals can refine the acicular ferrite and improve the impact toughness.
Explosive Vomiting Associated with Proximal Colonic Distention during a Difficult Propofol-Assisted Colonoscopy
Authors: Rah Kang H. , Ferges William , Tse James
Published: July 2019

We present a case of explosive vomiting associated with the extensive manipulation of the proximal colon during a difficult colonoscopy procedure. The cause of vomiting in this case may have been multifactorial; however, proximal colonic distention was the most likely factor because the onset of vomiting coincided with proximal colonic manipulation and happened without any prodromal signs, coughing, and airway obstruction. Propofol, the sedative most commonly administered to the patient during colonoscopy, allows for a deep state of sedation, and consequently extensive colonic distention and scope manipulation. Colonic distention may lead to a higher risk of vomiting. We reviewed the neurocircuitry associated with vomiting and discussed why proximal colonic distention may increase the risk of vomiting. We emphasize vigilance during the manipulation of the proximal colon because vomiting increases the potential for aspiration pneumonitis and pneumonia in patients under deep propofol sedation with attenuated airway responses.
A Systems-Based Analysis of the CardioMEMS HF Sensor for Chronic Heart Failure Management
Authors: Tran Jeffrey S. , Wolfson Aaron M. , O’Brien Daniel , Yousefian Omid , Shavelle David M.
Published: July 2019

Background. Hemodynamic-guided therapy using the CardioMEMS™ system has been shown to reduce heart failure hospitalization (HFH) in both clinical trials and real-world settings. However, the CardioMEMS system requires input from multiple independent elements to achieve its effect, and no studies have been done to investigate those elements. Consistent patient participation and health care provider participation are two of those key elements, and this study sought to assess how they affect HFHs. Methods. This was a single-center, retrospective cohort study of patients with the CardioMEMS sensor. The primary outcome was the number of HFH days patients experienced in the 1 year following CardioMEMS sensor implant. The primary independent variables were the average number of days between patient transmissions of data and the average number of days between health care provider reviews of those data. Covariates included patient demographics, medical comorbidities, history of HFHs, and initial pressure response to hemodynamic-guided therapy at 28 days after implant. Data were fit to a zero-inflated negative binomial regression. Results. Seventy-eight patients were included in the study. The mean age was 64 ± 15 years, 52 (67%) were male, and 58 (76%) had heart failure with reduced ejection fraction. During the study period, there were 538 cumulative HFH patient-days. Based on the regression model, there was an exponential relationship between HFH days and the mean number of days between patient transmissions (IRR = 1.74, 95% CI: 1.09–2.75, p=0.019). There was also an exponential relationship between HFH days and the mean number of days between health care provider reviews (IRR = 1.03, 95% CI: 1.01–1.05, p=0.013). Conclusions. This single-center study suggests that more frequent patient transmissions and health care provider reviews of the CardioMEMS system are associated with a decreased number of HFH days, but larger multicentered studies are required. Further systems-based analyses of the CardioMEMS system may be a useful approach to guiding effective use of the CardioMEMS device.
Prior Appendectomy and the Onset and Course of Crohn’s Disease in Chinese Patients
Authors: Chen Dafan , Ma Jing , Ben Qiwen , Lu Lungen , Wan Xinjian
Published: July 2019

Background and Aim. The relationship between prior appendectomy and Crohn’s disease (CD) has previously revealed conflicting findings. The present study investigates the relationship between prior appendectomy and CD development in Chinese patients. Methods. A retrospective case-control study was performed to compare prior appendectomy rate between CD patients and age- and gender-matched controls at two Chinese hospitals. The clinical course of CD was determined in patients who underwent and did not undergo appendectomies before CD diagnosis. Results. A total of 617 CD patients and 617 controls were included. The appendectomy rate before CD diagnosis in patients was higher, when compared to controls (6.65% versus 3.73%, P=0.033). Appendectomy was a risk factor for the onset of CD independent of smoking in the multivariate analysis (OR: 1.878; 95% CI: 1.111–3.174; P=0.019). Appendectomies were performed closer to the date of CD diagnosis in the trend test (P=0.039). The rate of appendectomy within one year or 1-5 years before CD diagnosis was higher in patients when compared to that in controls (0.97% versus 0%, P=0.031; 1.13% versus 0.32%, P=0.180). However, the rate of appendectomy over five years before CD diagnosis was close to controls (4.54% versus 3.40%, P=0.392). No significant differences in disease location, behavior, medication, and intestinal resection between appendectomy and nonappendectomy CD patients were found, even in the subgroup analysis by age of appendectomy. Conclusion. Prior appendectomy is a risk factor for the onset of CD. However, the appendectomy rate only increased for a short duration before CD diagnosis, likely reflecting a diagnostic bias. Prior appendectomy did not influence the features or course of CD.
Identification of Serum miRNA-423-5p Expression Signature in Somatotroph Adenomas
Authors: Zhao Sida , Li Jianhua , Feng Jie , Li Zhenye , Liu Qian , Lv Peng , Wang Fei , Gao Hua , Zhang Yazhuo
Published: July 2019

Circulating miRNAs are novel disease biomarkers that are valuable for diagnosis and prognosis. But the circulating miRNAs profile in somatotroph adenomas is still unknown. Therefore, serum exosomal miRNAs expression profiling in somatotroph adenomas was performed on 6 somatotroph adenomas and 6 normal controls. From the exosomal miRNAs expression profiling, we found 169 miRNAs differently expressed between somatotroph adenomas and healthy pituitary samples (p< 0.05, FC > 2). Among the 169 miRNAs, miR-423-5p was expressed lower in somatotroph adenomas than in healthy pituitary samples, which was proved by miRSCan Panel Chip™ qPCR. PTTG1 and SYT1 were the target mRNAs of miR-423-5p, and transcriptomics and proteomics profile both indicated the high expression of PTTG1 and SYT1 in somatotroph adenomas. H-scores were 223.1 ± 34.7 for PTTG1 and 163.4 ± 42.3 for SYT1 in 62 somatotroph adenomas specimens and 84.2 ± 21.3 for PTTG1 and 47.4 ± 17.2 for SYT1 in 6 healthy pituitary specimens by IHC. miR-423-5p inhibited the expression of SYT1 and PTTG1 at the mRNA and protein levels. Dual luciferase reporter gene assay shown was significantly reduced in the presence of miR-423-5p in GH3 cells transfected with wild-type PTTG1 3'UTR luciferase reporter plasmid but not reduced when transfected with the mutation PTTG1 3'UTR luciferase reporter plasmid (p<0.01). In vitro experiments showed that miR-423-5p induced cell apoptosis, inhibited cell proliferation, and reduced growth hormone release and migration of GH3 cells. The activity of miR-423-5p in GH3 cell was nearly blocked by its inhibitor. These results verified the central role of low miR-423-5p in promoting tumorigenesis in somatotroph adenomas. PTTG1 may act as biomarkers for clinical treatment of somatotroph adenomas.
Effects of Hibiscus Sabdariffa Calyces Aqueous Extract on the Antihypertensive Potency of Captopril in the Two-Kidney-One-Clip Rat Hypertension Model
Authors: Nurfaradilla Shinta Ayu , Saputri Fadlina Chany , Harahap Yahdiana
Published: July 2019

Hibiscus sabdariffa aqueous extract (HS) is often used as complementary therapy for hypertension. However, some studies have shown that coadministration with a conventional antihypertensive drug can affect drug potency. We compared the effects of HS plus captopril (CAP) coadministration to HS and CAP administration alone on blood pressure and renin-angiotensin-aldosterone system (RAAS) biomarkers in the rat two-kidney-one-clip (2K1C) model of hypertension. Male Sprague Dawley rats were randomly divided into seven groups (n=6/group), a normal control (SHAM) group, and six 2K1C groups. In 2K1C animals, hypertension was induced using a stainless microclip (inner diameter of 0.20 mm). Four weeks after 2K1C surgery, blood pressure was significantly higher than in the SHAM group. Then, model rats were randomly divided into negative control (2K1C, no treatment), positive control (4.5 mg captopril/200 g body weight [BW] orally [p.o.]), HS alone (30 mg/200 g BW; p.o.), and 3 co-treatment groups receiving HS (15, 30, or 60 mg/200 g BW; p.o.) plus 4.5 mg/200 g BW captopril. The treatments were performed for two weeks. Blood pressure was significantly reduced by all the drug treatments to near the level of SHAM controls. Plasma renin level, serum angiotensin converting enzyme (ACE) activity, and plasma angiotensin II level were also significantly elevated in the 2K1C group compared to the SHAM group. Both serum ACE activity and plasma angiotensin II level were significantly reduced to near SHAM group levels by all the drug treatments. Hibiscus sabdariffa aqueous extract alone can reduce blood pressure. This extract appears could be used as a supplement with captopril but may not provide any additional benefit.
AI-Assisted In Situ Detection of Human Glioma Infiltration Using a Novel Computational Method for Optical Coherence Tomography
Authors: Juarez-Chambi Ronald M. , Kut Carmen , Rico-Jimenez Jose J. , Chaichana Kaisorn L. , Xi Jiefeng , Campos-Delgado Daniel U. , Rodriguez Fausto J. , Quinones-Hinojosa Alfredo , Li Xingde , Jo Javier A.
Published: July 2019

Purpose:

In glioma surgery, it is critical to maximize tumor resection without compromising adjacent noncancerous brain tissue. Optical coherence tomography (OCT) is a noninvasive, label-free, real-time, high-resolution imaging modality that has been explored for glioma infiltration detection. Here, we report a novel artificial intelligence (AI)-assisted method for automated, real-time, in situ detection of glioma infiltration at high spatial resolution.

Experimental Design: Volumetric OCT datasets were intraoperatively obtained from resected brain tissue specimens of 21 patients with glioma tumors of different stages and labeled as either noncancerous or glioma-infiltrated on the basis of histopathology evaluation of the tissue specimens (gold standard). Labeled OCT images from 12 patients were used as the training dataset to develop the AI-assisted OCT-based method for automated detection of glioma-infiltrated brain tissue. Unlabeled OCT images from the other 9 patients were used as the validation dataset to quantify the method detection performance.

Results:

Our method achieved excellent levels of sensitivity (∼100%) and specificity (∼85%) for detecting glioma-infiltrated tissue with high spatial resolution (16 μm laterally) and processing speed (∼100,020 OCT A-lines/second).

Conclusions:

Previous methods for OCT-based detection of glioma-infiltrated brain tissue rely on estimating the tissue optical attenuation coefficient from the OCT signal, which requires sacrificing spatial resolution to increase signal quality, and performing systematic calibration procedures using tissue phantoms. By overcoming these major challenges, our AI-assisted method will enable implementing practical OCT-guided surgical tools for continuous, real-time, and accurate intraoperative detection of glioma-infiltrated brain tissue, facilitating maximal glioma resection and superior surgical outcomes for patients with glioma.
Nivo-lution in Mesothelioma
Authors: Mansfield Aaron S. , Zauderer Marjorie G.
Published: July 2019

The MERIT study was a single-arm, phase II clinical trial of nivolumab for the second- or third-line treatment of patients with malignant pleural mesothelioma in Japan. MERIT confirmed that PD-1 inhibition has activity in mesothelioma and led to the regulatory approval of nivolumab for the treatment of mesothelioma in Japan.

See related article by Okada et al., p. 5485
Tumor Genomic Profiling Guides Patients with Metastatic Gastric Cancer to Targeted Treatment: The VIKTORY Umbrella Trial
Authors: Lee Jeeyun , Kim Seung Tae , Kim Kyung , Lee Hyuk , Kozarewa Iwanka , Mortimer Peter G.S. , Odegaard Justin I. , Harrington Elizabeth A. , Lee Juyoung , Lee Taehyang , Oh Sung Yong , Kang Jung-Hun , Kim Jung Hoon , Kim Youjin , Ji Jun Ho , Kim Young Saing , Lee Kyoung Eun , Kim Jinchul , Sohn Tae Sung , An Ji Yeong , Choi Min-Gew , Lee Jun Ho , Bae Jae Moon , Kim Sung , Kim Jae J. , Min Yang Won , Min Byung-Hoon , Kim Nayoung K.D. , Luke Sally , Kim Young Hwa , Hong Jung Yong , Park Se Hoon , Park Joon Oh , Park Young Suk , Lim Ho Yeong , Talasaz AmirAli , Hollingsworth Simon J. , Kim Kyoung-Mee , Kang Won Ki
Published: July 2019

The VIKTORY (targeted agent eValuation In gastric cancer basket KORea) trial was designed to classify patients with metastatic gastric cancer based on clinical sequencing and focused on eight different biomarker groups (RAS aberration, TP53 mutation, PIK3CA mutation/amplification, MET amplification, MET overexpression, all negative, TSC2 deficient, or RICTOR amplification) to assign patients to one of the 10 associated clinical trials in second-line (2L) treatment. Capivasertib (AKT inhibitor), savolitinib (MET inhibitor), selumetinib (MEK inhibitor), adavosertib (WEE1 inhibitor), and vistusertib (TORC inhibitor) were tested with or without chemotherapy. Seven hundred seventy-two patients with gastric cancer were enrolled, and sequencing was successfully achieved in 715 patients (92.6%). When molecular screening was linked to seamless immediate access to parallel matched trials, 14.7% of patients received biomarker-assigned drug treatment. The biomarker-assigned treatment cohort had encouraging response rates and survival when compared with conventional 2L chemotherapy. Circulating tumor (ctDNA) analysis demonstrated good correlation between high MET copy number by ctDNA and response to savolitinib.

Significance:

Prospective clinical sequencing revealed that baseline heterogeneity between tumor samples from different patients affected response to biomarker-selected therapies. VIKTORY is the first and largest platform study in gastric cancer and supports both the feasibility of tumor profiling and its clinical utility.

This article is highlighted in the In This Issue feature, p. 1325
Responsiveness to Change of the Montreal Cognitive Assessment, Mini-Mental State Examination, and SCOPA-Cog in Non-Demented Patients with Parkinson’s Disease
Authors: Faust-Socher Achinoam , Duff-Canning Sarah , Grabovsky Arthur , Armstrong Melissa J. , Rothberg Brandon , Eslinger Paul J. , Meaney Christopher A. , Schneider Ruth B. , Tang-Wai David F. , Fox Susan H. , Zadikoff Cindy , Kennedy Nancy , Chou Kelvin L. , Persad Carol , Litvan Irene , Mast Benjamin T. , Gerstenecker Adam T. , Weintraub Sandra , Reginold William , Marras Connie
Published: July 2019

Background: Clinical monitoring of patients with Parkinson’s disease (PD) for cognitive decline is an important element of care. The Montreal Cognitive Assessment (MoCA) has been proposed to be a sensitive tool for assessing cognitive impairment in PD. The aim of our study was to compare the responsiveness of the MoCA to decline in cognition to the responsiveness of the Mini Mental State Examination (MMSE) and the Scales for Outcomes of Parkinson’s disease-cognition (SCOPA-Cog). Methods: PD patients without dementia were enrolled at 6 North American movement disorders centers between 2008 and 2011. Participants received annual evaluations including the MoCA, MMSE, and SCOPA-Cog followed by formal neuropsychological testing. The gold standard for change in cognition was defined as the change on the neuropsychological test scores over the annual assessments. The Reliable Change Method was used to provide an estimate of the probability that a given difference score would be obtained by chance. The sensitivity of the MoCA, MMSE, and SCOPA-Cog to change was quantified using receiver operating characteristics (ROC) curves. Results: One hundred seventeen patients were included in the analysis. Participants were followed at mean intervals of 11 ± 2 months for a median of 2 (maximum 5) visits. According to the reliable change index, 56 intervals of cognitive testing showed a decline in global cognition. ROC analysis of change in MoCA, MMSE, and SCOPA-Cog global scores compared to gold standard testing found an area under the curve (AUC) of 0.55 (95% CI 0.48–0.62), 0.56 (0.48–0.63), and 0.63 (0.55–0.70) respectively. There were no significant differences in the AUCs across the tests. The sensitivity of the MoCA, MMSE, and SCOPA-Cog to change at various thresholds for decline in scores reached a maximum of 71% for a cut-off of 1 point change on the SCOPA-Cog. Conclusion: Using neuropsychological testing as a gold standard comparator, the performance of the MoCA, MMSE, and SCOPA-Cog for detecting decline in non-demented PD patients over a 1-year interval is poor. This has implications for clinical practice; stable scores may not be taken as reassurance of the absence of cognitive decline.
Pigmented Villonodular Synovitis Presenting as Unilateral Hearing Loss: Review of the Literature and Case Report
Authors: Brant Jason A. , Kaufman Adam C. , Luu Neil , Grady Sean M. , O'Malley Bert W. , Ruckenstein Michael J.
Published: July 2019

Background/Aims: To review the existing literature on pigmented villonodular synovitis (PVNS) of the temporomandibular joint (TMJ) and report a rare case of PVNS of the TMJ presenting with unilateral hearing loss. Methods: Review of the existing literature and a description of personal experience with PVNS of the TMJ presenting with unilateral hearing loss. Results: Review of the existing literature revealed 76 reported cases of PVNS of the TMJ. The most common presenting symptom was of a slowly enlarging mass or swelling of the preauricular area, with dysfunctional TMJ also frequently reported. All patients underwent surgical excision with some pursuing radiation as adjuvant therapy. Presented Patient: A 46-year-old man presented with several months of unilateral subjective hearing loss and aural fullness. Imaging revealed a mass centered along the superior TMJ with expansion through the squamous temporal bone and extra-axial intracranial extension into the middle cranial fossa. Imaging characteristics and fine-needle aspiration biopsy were consistent with PVNS. Intervention: The patient underwent near-total excision of the mass via frontotemporal craniectomy and lateral temporal bone resection. Follow-Up: At the 16-month follow-up there was no evidence of disease recurrence. Conclusion: PVNS of the TMJ represents a rare entity that can present with a variety of symptoms including unilateral hearing loss.
Albumin and Hemoglobin Trajectories and Incident Disabling Dementia in Community-Dwelling Older Japanese
Authors: Taniguchi Yu , Kitamura Akihiko , Kaito Sho , Yokoyama Yuri , Yokota Isao , Shinozaki Tomohiro , Seino Satoshi , Murayama Hiroshi , Matsuyama Yutaka , Ikeuchi Tomoko , Fujiwara Yoshinori , Shinkai Shoji
Published: July 2019

Background: Serum albumin and hemoglobin levels are independently associated with subsequent cognitive deterioration in older adults. This prospective study used repeated measures analysis to identify aging trajectories in serum albumin and hemoglobin levels and investigated if these trajectories were associated with incident disabling dementia among community-dwelling older Japanese. Methods: A total of 2,005 adults aged 65–90 years participated in annual geriatric health assessments during the period from June 2002 through July 2017; the total number of observations was 9,330. A review of a municipal database of the Japanese public long-term care insurance system identified 1,999 of 2,005 adults without dementia at baseline, 278 (13.9%) of whom developed disabling dementia during the follow-up period (June 2002 through December 2017). Results: We identified three trajectory patterns (high, moderate, and low) for serum albumin and hemoglobin levels for the age period 65 through 90 years. After controlling for potential confounders, participants with moderate and low trajectories for serum albumin level had hazard ratios of 1.27 (95% confidence interval 0.94–1.72) and 2.07 (1.37–3.11), respectively, for the development of incident disabling dementia, with the high trajectory group as reference. The respective hazard ratios for hemoglobin level were 1.31 (0.93–1.85) and 1.58 (1.04–2.40), respectively. Conclusion: Dementia risk was higher for individuals with low trajectories for serum albumin and hemoglobin levels. This finding highlights the importance of interventions that improve nutritional status and control relevant diseases in middle-aged and older adults with low serum albumin and hemoglobin levels.
Meta-Analysis of the Effect of the Clinical Pathway Applied to Patients with Endoscopic Sinus Surgery in China
Authors: Yong-Mei Bai , De-Min Han , Dong-Bo Wang , Qi-Zhi Ma , Yue-Da Pan
Published: July 2019

Background: Chronic rhinosinusitis (CRS) is one of the most common diseases in China. The incidence of CRS in the Chinese urban population is between 5 and 15%. It is difficult to cure with traditional surgery. Endoscopic sinus surgery is the first choice for the treatment of CRS. Compared with developed countries, the development of the clinical pathway of endoscopic sinus surgery in China is still unclear. Objectives: The aim is to explore whether the clinical pathway of endonasal sinus surgery is better than the traditional one in the Chinese population. Methods: We searched PubMed, Embase, the Cochrane Library, Web of Science, ClinicalTrials.gov, SinoMed, China National Knowledge Internet, Wanfang database of Chinese Journals, and VIP database of Chinese Journals. The last retrieval date was August 24, 2018. Review Manager 5.3 software was used for comprehensive quantification data analysis. Results: Fourteen papers involving 1,882 patients were included in this study. The results showed that compared with the traditional pathway, the clinical pathway can effectively shorten the average number of hospitalization days (mean difference, MD = –2.00, 95% CI: –2.50, –1.49). In total, 10 of the 14 papers, with a total of 1,500 patients, proved that the clinical pathway can effectively reduce the hospitalization costs of patients (standard mean difference, SMD = –3.15, 95% CI: –4.20, –2.10); 11 of the 14 papers, with a total of 1,488 patients, proved that the clinical pathway can effectively improve patients’ knowledge of health (95% CI:1.03, 1.09); and 7 of the 14 papers, with a total of 810 patients, proved that the clinical pathway can effectively improve patient satisfaction (95% CI:1.10, 1.20). Conclusions: Our systematic review and meta-analysis support the use of the clinical pathway in patients with endoscopic sinus surgery in China.
Free-Cog: Pragmatic Test Accuracy Study and Comparison with Mini-Addenbrooke’s Cognitive Examination
Authors: Larner Andrew J.
Published: July 2019

Background/Aims: Canonical definitions of the dementia construct encompass deficits in both cognition and function, but most screening instruments for possible dementia address only cognitive abilities. Free-Cog is a recently described brief screening instrument for dementia designed to address not only cognitive but also functional abilities. Methods: A pragmatic test accuracy study of Free-Cog was undertaken in consecutive patients seen over 1 year in a secondary care setting. The performance of Free-Cog for diagnosis of dementia and mild cognitive impairment (MCI) was compared to that of Mini-Addenbrooke’s Cognitive Examination (MACE). Results: In a cohort of 141 patients (prevalence of dementia and MCI 11 and 32%, respectively) both Free-Cog and MACE were quick and easy to use and acceptable to patients. Both tests had high sensitivity (1.00) and large effect sizes (Cohen’s d) for diagnosis of dementia, but Free-Cog was more specific. For diagnosis of MCI, Free-Cog lacked sensitivity (0.58) but was specific (0.81), whereas MACE was sensitive (0.91) but not specific (0.35). Weighted comparison suggested equivalence for dementia diagnosis but a net benefit for MACE regarding MCI diagnosis. Conclusion: Free-Cog is an acceptable and accurate test for dementia screening in a dedicated cognitive disorders clinic, but it appears less sensitive than MACE for the identification of MCI.
The Role of Tumor-Associated Macrophages in Leukemia
Authors: Li Yueyang , You M. James , Yang Yaling , Hu Dongzhi , Tian Chen
Published: July 2019

In addition to intrinsic factors, leukemia cell growth is influenced by the surrounding nonhematopoietic cells in the leukemic microenvironment, including fibroblasts, mesenchymal stem cells, vascular cells, and various immune cells. Despite the fact that macrophages are an important component of human innate immunity, tumor-associated macrophages (TAMs) have long been considered as an accomplice promoting tumor growth and metastasis. TAMs are activated by an abnormal malignant microenvironment, polarizing into a specific phenotype and participating in tumor progression. TAMs that exist in the microenvironment of different types of leukemia are called leukemia-associated macrophages (LAMs), which are reported to be associated with the progression of leukemia. This review describes the role of LAMs in different leukemia subtypes.
Phospholipase A2 Receptor Antibody IgG4 Subclass Improves Sensitivity and Specificity in the Diagnosis of Idiopathic Membranous Nephropathy
Authors: Huang Biao , Zhang Yi , Wang Liang , Xu Wenwei , Zhang Jue , Zhang Qiuhua , Sheng Huiming , Hu Zhigang
Published: July 2019

Aims: The aim of this study was to develop a new method for detecting anti-phospholipase A2 receptor-IgG4 to improve the sensitivity and specificity in the diagnosis of idiopathic membranous nephropathy (IMN). Methods: A highly sensitive quantitative assay was developed for the detection of serum anti-phospholipase A2 receptor-IgG4 with europium chelation by time-resolved fluoroimmunoassay (TRFIA), and a mouse anti-human IgG4 tracer was prepared using europium chelation for detection. The specificity and sensitivity of anti-phospholipase A2 receptor-IgG4 in the diagnosis of IMN were further assessed in patients with different kidney diseases. Results: The detection limit of anti-PLA2R-IgG4 was 0.69 ng/mL. The measurement range of anti-PLA2R-IgG4 TRFIA was 0.69–2,500 ng/mL. Mean serum anti-PLA2R-IgG4 was 21.27 ± 15.15 ng/mL in 45 healthy volunteers, 31.08 ± 18.17 ng/mL in 29 IgA nephropathy patients, 49.10 ± 34.32 ng/mL in 8 lupus nephropathy patients, and 10,324.11 ± 17,030.40 ng/mL in 30 IMN patients. The anti-PLA2R-IgG4 cutoff concentration was >161.2 ng/mL with the sensitivity of 90.0% and specificity of 100% in the diagnosis of IMN. However, the cutoff for other kidney diseases was lower than 161.2 ng/mL. Conclusion: The serum anti-phospholipase A2 receptor IgG4 detected with the method developed in this study has higher sensitivity and higher specificity than total IgG in the diagnosis of IMN.
Lemierre’s Syndrome Caused by Streptococcus anginosus Presenting as Postseptal Cellulitis in a Pediatric Patient
Authors: Camacho-Cruz Jhon , Preciado Helen , Beltrán Natalia , Fierro Laura , Carrillo Jorge
Published: July 2019

Lemierre’s syndrome is an infrequent disease characterized by septic thrombosis of the internal jugular vein followed by pulmonary embolism generally occurring after upper respiratory and gastrointestinal tract infections. We present the case of a 15-year-old female patient with postseptal cellulitis and cervical abscess who developed pulmonary embolism and pleural effusion secondary to internal jugular vein thrombosis. Cultures were positive for Streptococcus anginosus, antibiotic treatment was established with satisfactory clinical outcome. High clinical suspicion is required for a diagnosis. The mainstay of treatment is a multidisciplinary approach based on two essential pillars: antibiotic therapy and surgical drainage. This is an important case because of the unusual presentation, the isolation of an infrequent pathogen, and the primary infection site (postseptal cellulitis), which are rare characteristics of this condition in the pediatric population.
Distinct Patterns of Hippocampal and Neocortical Evolution in Primates
Authors: Vanier David R. , Sherwood Chet C. , Smaers Jeroen B.
Published: July 2019

Because of the central role of the hippocampus in representing spatial and temporal details of experience, comparative studies of its volume and structure are relevant to understanding the evolution of representational memory across species. The hippocampal formation, however, is organized into separate anatomical subregions with distinct functions, and little is known about the evolutionary diversification of these subregions. We investigate relative volumetric changes in hippocampal subregions across a large sample of primate species. We then compare the evolution of the hippocampal formation to the neocortex. Results across hippocampal subregions indicate that, compared to strepsirrhines, the anthropoid lineage displays a decrease in relative CA3, fascia dentata, subiculum, and rhinal cortex volume in tandem with an increase in relative neocortical volume. These findings indicate that hippocampal function in anthropoids might be substantially augmented by the executive decision-making functions of the neocortex. Humans are found to have a unique cerebral organization combining increased relative CA3, subiculum, and rhinal cortex with increased relative neocortical volumes, suggesting that these regions may play a role in behaviors that are uniquely specialized in humans.
Fluctuating Sensorineural Hearing Loss
Authors: Liu Hui , Zhou Kunpeng , Zhang Xuemei , Peng Kevin A.
Published: July 2019

Background: Several otologic conditions can present with fluctuating sensorineural hearing loss, including Ménière’s disease, autoimmune inner ear disease, and enlarged vestibular aqueduct. Although these 3 etiologies vary greatly, distinguishing between these conditions at initial presentation can be challenging. Furthermore, initial treatment of these conditions is often similar. In this review, we discuss historical and current perspectives on diagnosis and treatment of these conditions. Summary: A literature search was performed regarding fluctuating hearing loss, and current treatment of these etiologies of fluctuating hearing loss was summarized. Immediate measures at the onset of acute hearing loss include corticosteroid therapy, while preventative and chronic therapies, which can limit disease severity and frequency, vary based on the specific condition treated. Key Messages: Fluctuating hearing loss can represent a range of pathologies, but the precise etiology may not be clear at initial presentation. Timely treatment and long-term follow-up, along with appropriate diagnostics, are necessary to optimize long-term hearing.
Efficacy and Safety of Cetuximab plus Radiotherapy in Cisplatin-Unfit Elderly Patients with Advanced Squamous Cell Head and Neck Carcinoma: A Retrospective Study
Authors: Addeo Raffaele , Caraglia Michele , Vincenzi Bruno , Luce Amalia , Montella Liliana , Mastella Amerigo , Mazzone Salvatore , Ricciardiello Filippo , Carraturo Marco , Del Prete Salvatore , Sperlongano Pasquale
Published: July 2019

Introduction: Concurrent platinum-based chemoradiation currently represents the standard treatment for advanced head and neck cancer (HNC), but it induces a significant toxicity, in particular among elderly patients. Elderly and unfit patients have been underrepresented in clinical trials and there is a need for tailored guidelines. Methods: A retrospective review of clinical data of HNC patients treated at the Operative Oncology Unit of the San Giovanni di Dio Hospital in Frattamaggiore (Naples, Italy) was performed. At study entry, a comprehensive assessment including absolute contraindications for cisplatin use, as well as comorbidities, socioeconomic status, BMI, and weight loss, was performed. The treatment included high-dose radiotherapy plus weekly cetuximab (initially at a dose of 400 mg/m2of body surface area and thereafter at 250 mg weekly during the whole radiotherapy). The aim of this study was to evaluate the activity and toxicity of this schedule in a series of patients aged older than 69 years. Results: Between May 30, 2013, and March 30, 2015, sixty-four patients (age range, 69–87 years; median age, 73.7 years; male/female ratio, 46/18) were treated. The overall response rate was 67% in this series of patients. The disease control rate was 76%. Disease progression was recorded in 25% of the patients. The median duration of loco-regional control was 17 months (range, 15.8–17.7 months). PFS was 14.8 months (range, 13.9–15.5 months). The overall survival was 34 months, with a median follow-up of 41.0 months (range, 31.1–36.8 months). The main grade 3/4 adverse events were acne rash in 52% and radiation dermatitis in 32% of the cases. Conclusion: Cetuximab plus radiotherapy appears to be feasible and active in elderly patients unsuitable for cisplatin treatment. The treatment was supported by a favorable toxicity profile.
Retinoschisis: A Predictive Factor in Vitrectomy for Lamellar Macular Holes in Highly Myopic Eyes
Authors: Tao Jiwei , Wu Hanfei , Chen Huan , Li Gaochun , Chen Yiqi , Mao Jianbo , Shen Lijun
Published: July 2019

Purpose: To evaluate the effect of pars plana vitrectomy (PPV) and internal limiting membrane (ILM) peeling for lamellar macular hole (LMH) with or without macular retinoschisis in highly myopic eyes. Methods: In this retrospective, consecutive case-control study, 21 highly myopic patients (22 eyes) with LMH were divided into two groups based on preoperative optical coherence tomography (OCT): the “flat group” had no macular retinoschisis (n = 10), and the “retinoschisis group” had macular retinoschisis (n = 12). The average follow-up time was 17.2 ± 12.6 months. Outcomes were based on 6-month postoperative best-corrected visual acuity (BCVA), integrity of the ellipsoid zone (EZ), external limiting membrane (ELM), and residual foveal thickness (RFT). Results: The appearance of the macula on OCT was normalized in 19 eyes (86.3%) at the final follow-up visit. Compared to the flat group, the retinoschisis group presented a significantly higher incidence of epiretinal membrane (p = 0.046) and lower refractive error (p = 0.033), shorter axial length (p = 0.0009), better integrity of ELM and EZ (p = 0.005 and p = 0.005, respectively), and better preoperative and postoperative BCVAs (p = 0.015). Conclusions: PPV is an effective method to achieve a high anatomical success, improve postoperative vision, and prevent foveal thinning in highly myopic eyes with LMH. In these eyes, the presence of retinoschisis strongly indicates the need for vitrectomy.
Changes in Hearing Threshold and Tinnitus Severity after Stapes Surgery: Which Is More Important to the Patient’s Quality of Life?
Authors: Dziendziel Beata , Skarzynski Henryk , Gos Elzbieta , Skarzynski Piotr H.
Published: July 2019

Background: Stapes surgery is a common method of treatment of otosclerosis, and its effectiveness is reported based on audiometric hearing thresholds. Audiometric tests do not gauge the impact of tinnitus severity and auditory function on quality of life (QOL) after stapes surgery. Objective: To measure self-assessed QOL in otosclerosis patients after stapedotomy in terms of three major factors: change in audiometric hearing threshold, subjective hearing benefit, and tinnitus severity. Method: This prospective clinical study included 191 patients who underwent stapedotomy between April and October 2017 due to otosclerosis. All patients were tested by pure tone audiometry and filled in a questionnaire before surgery and 6 months afterwards. Subjective hearing was assessed with the Abbreviated Profile for Hearing Aid Benefit (APHAB); tinnitus severity was established using the Tinnitus Functional Index (TFI), and the QOL was measured by the Glasgow Benefit Inventory (GBI). Results: Statistical analysis showed that the average GBI total score (mean = 33.7; SD = 23.7) was statistically significantly higher than zero (t = 19.7; p < 0.001). Based on a regression model, all the three variables studied – audiometric hearing thresholds change, APHAB change, and TFI change – had a significant effect on QOL after stapedotomy. Interestingly, the highest beta value (b = 0.040; p < 0.001) was for TFI change, implying that TFI change had the greatest effect on QOL. Conclusion: Although the improvement of QOL after stapes surgery undoubtedly depended on improvement in both audiometric and self-reported hearing, the reduction of tinnitus severity had the greatest impact on increase in QOL.
The Value of Three-Dimensional Brain Volume Combined with Time-of-Flight MRA in Microvascular Decompression
Authors: Li Jun , Wang Ying , Lian Zhigang , Liu Rongyao , Liang Zhanhua , Song Chunli , Song Qingwei , Wei Zhenqing
Published: July 2019

Objectives: To explore the guidance value of preoperative 3-dimensional brain volume (3D-BRAVO) and 3-dimensional time-of-flight (3D-TOF) MRA scanning for microvascular decompression. Methods: One hundred thirteen patients treated with microvascular decompression from February 2016 to February 2018 in the First Affiliated Hospital of Dalian Medical University were retrospectively analyzed. All patients received 3D-BRAVO combined with 3D-TOF MRA sequence reconstruction before the operation. The anatomical relationship of neurovascular tissues was analyzed and compared with the results of intraoperative exploration. Results: The results of MVD showed that the number of positive cases was 108 (95.6%) on the diseased side. 3D-BRAVO combined with 3D-TOF sequence reconstruction resulted in 106 positive cases (93.8%), with a 98.1% positive coincidence rate and a 13.2% false positive rate (p < 0.05). 3D-BRAVO-TOF sequence reconstruction of trigeminal neuralgia showed a positive coincidence in 78 cases (92.8%) and for hemifacial spasm a positive coincidence was found in 27 cases (93.1%). Conclusion: 3D-BRAVO combined with 3D-TOF sequence reconstruction before microvascular decompression can fully evaluate the morphology, location, and anatomical relationship of lesions, which is of guidance value for clinical diagnosis and treatment.