bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Tissue Kallikreins: Physiologic Roles and Applications in Cancer
Authors: Borgoño Carla A. , Michael Iacovos P. , Diamandis Eleftherios P.
Published: May 2022

Tissue kallikreins are members of the S1 family (clan SA) of trypsin-like serine proteases and are present in at least six mammalian orders. In humans, tissue kallikreins (hK) are encoded by 15 structurally similar, steroid hormone–regulated genes (KLK) that colocalize to chromosome 19q13.4, representing the largest cluster of contiguous protease genes in the entire genome. hKs are widely expressed in diverse tissues and implicated in a range of normal physiologic functions from the regulation of blood pressure and electrolyte balance to tissue remodeling, prohormone processing, neural plasticity, and skin desquamation. Several lines of evidence suggest that hKs may be involved in cascade reactions and that cross-talk may exist with proteases of other catalytic classes. The proteolytic activity of hKs is regulated in several ways including zymogen activation, endogenous inhibitors, such as serpins, and via internal (auto)cleavage leading to inactivation. Dysregulated hK expression is associated with multiple diseases, primarily cancer. As a consequence, many kallikreins, in addition to hK3/PSA, have been identified as promising diagnostic and/or prognostic biomarkers for several cancer types, including ovarian, breast, and prostate. Recent data also suggest that hKs may be causally involved in carcinogenesis, particularly in tumor metastasis and invasion, and, thus, may represent attractive drug targets to consider for therapeutic intervention.
TEL/AML1 Overcomes Drug Resistance Through Transcriptional Repression of Multidrug Resistance-1 Gene Expression
Authors: Asakura Keiko , Uchida Hideo , Miyachi Hayato , Kobayashi Hiroyuki , Miyakawa Yoshitaka , Nimer Stephen D. , Takahashi Hiroyuki , Ikeda Yasuo , Kizaki Masahiro
Published: May 2022

The t(12;21)(p12;q22) chromosomal aberration, which is frequently observed in pediatric precursor B-cell acute lymphoblastic leukemia (ALL), generates the TEL/AML1 chimeric gene and protein. TEL/AML1-positive ALL has a favorable prognosis, and one possible reason is that this subtype of ALL rarely shows drug resistance. AML1/ETO, another AML1-containing chimeric protein, has been shown to transcriptionally repress the activity of the multidrug resistance-1 (MDR-1) gene promoter; thus, we examined whether TEL/AML1 also represses MDR-1 gene expression, possibly preventing the emergence of multidrug resistance. In this study, we show that the TEL/AML1 protein binds to the consensus AML1 binding site in the MDR-1 promoter and transcriptionally represses its activity. Following transient transfection of TEL/AML1 protein into Adriamycin-resistant K562/Adr cells, we also demonstrate that TEL/AML1 can down-regulate the expression of P-glycoprotein, a product of the MDR-1 gene, and restore the chemosensitivity to the cells. Furthermore, we report that MDR-1 mRNA levels in leukemic cells obtained from TEL/AML1-positive ALL patients are lower than those from TEL/AML1-negative ALL patients. Thus, TEL/AML1 protein acts as a transcriptional repressor of MDR-1 gene expression, and although TEL/AML1 has been implicated in leukemogenesis, its effects on the MDR-1 gene may contribute to the excellent prognosis of TEL/AML1-positive ALL with current therapy.
c-myb Heterozygous Mice Are Hypersensitive to 5-Fluorouracil and Ionizing Radiation
Authors: Ramsay Robert G. , Micallef Suzanne , Lightowler Sally , Mucenski Michael L. , Mantamadiotis Theo , Bertoncello Ivan
Published: May 2022

Hypersensitivity to chemo- and radiotherapy employed during cancer treatment complicates patient management. Identifying mutations in genes that compromise tissue recovery would rationalize treatment and may spare hypersensitive patients undue tissue damage. Genes that govern stem cell homeostasis, survival, and progenitor cell maintenance are of particular interest in this regard. We used wild-type and c-myb knock-out mice as model systems to explore stem and progenitor cell numbers and sensitivity to cytotoxic damage in two radiosensitive tissue compartments, the bone marrow and colon. Because c-myb null mice are not viable, we used c-myb heterozygous mice to test for defects in stem-progenitor cell pool recovery following γ-radiation and 5-fluorouracil treatment, showing that c-myb+/− mice are hypersensitive to both agents. While apoptosis is comparable in mutant and wild-type mice following radiation exposure, the crypt beds of c-myb+/− mice are markedly depleted of proliferating cells. Extrapolating from these data, we speculate that acute responses to cytotoxic damage in some patients may also be attributed to compromised c-myb function.
Protease-Activated Receptors (PAR1 and PAR2) Contribute to Tumor Cell Motility and Metastasis
Authors: Shi Xiaoli , Gangadharan Beena , Brass Lawrence F. , Ruf Wolfram , Mueller Barbara M.
Published: May 2022

The effects of the pleiotropic serine protease thrombin on tumor cells are commonly thought to be mediated by the thrombin receptor protease-activated receptor 1 (PAR1). We demonstrate here that PAR1 activation has a role in experimental metastasis using the anti-PAR1 antibodies ATAP2 and WEDE15, which block PAR1 cleavage and activation. Thrombin also stimulates chemokinesis of human melanoma cells toward fibroblast conditioned media and soluble matrix proteins. Thrombin-enhanced migration is abolished by anti-PAR1 antibodies, demonstrating that PAR1 cleavage and activation are required. The PAR1-specific agonist peptide TFLLRNPNDK, however, does not stimulate migration, indicating that PAR1 activation is not sufficient. In contrast, a combination of TFLLRNPNDK and the PAR2 agonist peptide SLIGRL mimics the thrombin effect on migration, whereas PAR2 agonist alone has no effect. Agonist peptides for the thrombin receptors PAR3 and PAR4 used alone or with PAR1 agonist also have no effect. Similarly, activation of PAR1 and PAR2 also enhances chemokinesis of prostate cancer cells. Desensitization with PAR2 agonist abolishes thrombin-enhanced cell motility, demonstrating that thrombin acts through PAR2. PAR2 is cleaved by proteases with trypsin-like specificity but not by thrombin. Thrombin enhances migration in the presence of a cleavage-blocking anti-PAR2 antibody, suggesting that thrombin activates PAR2 indirectly and independent of receptor cleavage. Treatment of melanoma cells with trypsin or PAR2 agonist peptide enhances experimental metastasis. Together, these data confirm a role for PAR1 in migration and metastasis and demonstrate an unexpected role for PAR2 in thrombin-dependent tumor cell migration and in metastasis.
Interleukin-10 Induced Activating Transcription Factor 3 Transcriptional Suppression of Matrix Metalloproteinase-2 Gene Expression in Human Prostate CPTX-1532 Cells
Authors: Stearns Mark E. , Kim Greg , Garcia Fernando , Wang Min
Published: May 2022

Aberrant expression of the 72-kDa type IV collagenase [matrix metalloproteinase (MMP)-2] is implicated in the invasion and angiogenesis process of malignant tumors. We investigated the effects of interleukin (IL)-10 on MMP-2 expression in CPTX-1532 human prostate tumor cells. Our results demonstrate that IL-10 significantly inhibited MMP-2 transcription and protein expression induced by a phorbol ester, phorbol 12-myristate 13-acetate. The inhibitory effects of IL-10 on MMP-2 expression correlated with the suppression of MMP-2 promoter activity. To determine the mechanism of IL-10 action, we examined IL-10–dependent promoter activity with luciferase constructs from a 2-kbp promoter region of the human MMP-2 gene. We functionally characterized the promoter fragments by transient transfection experiments with CPTX-1532 cells. The experiments revealed that a cAMP responsive element binding protein (CREB) consensus domain was identified upstream of the 5′ transcriptional start site, which was highly responsive to IL-10–dependent down-regulation of promoter luciferase activity. Electrophoretic mobility shift assays combined with antibody “supershift assays” confirmed the data from the luciferase assays. Immunoblot assays of activating transcription factor (ATF) 3 immunoprecipitates with tyrosine specific antibodies revealed that IL-10 stimulated tyrosine phosphorylation of ATF3 to activate binding to the CREB domain and suppress MMP-2 expression. Studies with stable, IL-10 transfected CPTX-1532 subclones further showed that IL-10 failed to suppress MMP-2 expression in ATF3-deficient CPTX-1532 cells, where the ATF3 mRNA was destroyed with a DNAzyme oligonucleotide targeting the 5′ region of the mRNA. Finally, reconstitution of ATF3 successfully restored the inhibitory effects of IL-10 on MMP-2 gene expression. Taken together, these data demonstrate the critical role of tyrosine phosphorylated ATF3 and the CREB consensus domain in IL-10 suppression of MMP-2 gene expression in primary human prostate tumor cells.
Polo-Like Kinase 1 Inactivation Following Mitotic DNA Damaging Treatments Is Independent of Ataxia Telangiectasia Mutated Kinase
Authors: Yuan Jin-Hui , Feng Yang , Fisher Rebecca H. , Maloid Sharon , Longo Dan L. , Ferris Douglas K.
Published: May 2022

Polo-like kinase 1 (Plk1) is an important regulator of several events during mitosis. Recent reports show that Plk1 is involved in both G2 and mitotic DNA damage checkpoints. Ataxia telangiectasia mutated kinase (ATM) is an important enzyme involved in G2 phase cell cycle arrest following interphase DNA damage, and inhibition of Plk1 by DNA damage during G2 occurs in an ATM-/ATM-Rad3–related kinase (ATR)–dependent fashion. However, it is unclear how Plk1 is regulated in response to M phase DNA damage. We found that treatment of mitotic cells with DNA damaging agents inhibits Plk1 activity primarily through dephosphorylation of Plk1, which occurred in both p53 wild-type and mutant cells. Inhibition of Plk1 is not prevented by caffeine pretreatment that inhibits ATM activity and also occurs in ATM mutant cell lines. Furthermore, ATM mutant cell lines, unlike wild-type cells, fail to arrest after mitotic DNA damaging treatments. The phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002, reduces Plk1 dephosphorylation following mitotic DNA damaging treatments, suggesting that the PI3K pathway may be involved in regulating Plk1 activity. Earlier studies showed that inhibition of Plk1 by G2 DNA damage occurs in an ATM-dependent fashion. Our results extend the previous studies by showing that ATM is not required for dephosphorylation and inhibition of Plk1 activity following mitotic DNA damage, and also suggest that Plk1 is not a principal regulator or mediator of the mitotic DNA damage response.
ERβ Sensitizes Breast Cancer Cells to Retinoic Acid: Evidence of Transcriptional Crosstalk
Authors: Rousseau Caroline , Nichol Jessica N. , Pettersson Filippa , Couture Marie-Claude , Miller Wilson H.
Published: May 2022

The ability of retinoids to inhibit breast cancer cell growth correlates with estrogen receptor (ER) α status, as shown by the antiproliferative effects of retinoids in ERα-positive breast cancer cells and their use as chemopreventive agents in premenopausal women. The discovery of ERβ, also present in breast cancer cells, has added a new level of complexity to this malignancy. To determine the retinoid response in ERβ-expressing breast cancer cells, we used retroviral transduction of ERβ in ER-negative MDA-MB-231 cells. Western blot and immunofluorescence confirmed expression and nuclear localization of ERβ, whereas functionality was shown using an estrogen response element–containing reporter. A significant retinoic acid (RA)–mediated growth inhibition was observed in the transduced ERβ-positive cells as shown by proliferation assays. Addition of estradiol, tamoxifen, or ICI 182,780 had no effect on cell growth and did not alter RA sensitivity. We observed that retinoids altered ERβ-mediated transcriptional activity from an estrogen response element, which was confirmed by decreased expression of the pS2 gene, and from an activator protein response element. Conversely, the expression of ERβ altered RA receptor (RAR) β expression, resulting in greater induction of RARβ gene expression on RA treatment, without altered expression of RARα. Our data provide evidence of transcriptional crosstalk between ERβ and RAR in ERβ-positive breast cancer cells that are growth inhibited by RA.
Hypermethylation of the Death-Associated Protein Kinase Promoter Attenuates the Sensitivity to Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Induced Apoptosis in Human Non–Small Cell Lung Cancer Cells
Authors: Tang Ximing , Wu Weiguo , Sun Shi-yong , Wistuba Ignacio I. , Hong Waun Ki , Mao Li
Published: May 2022

Death-associated protein (DAP) kinase plays an important role in IFN-γ, tumor necrosis factor (TNF)-α, or Fas–ligand induced apoptosis. TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF ligand family and can induce caspase-dependent apoptosis in cancer cells while sparing most of the normal cells. However, some of the cancer cell lines are insensitive to TRAIL, and such resistance cannot be explained by the dysfunction of TRAIL receptors or their known downstream targets. We reported previously that DAP kinase promoter is frequently methylated in non-small cell lung cancer (NSCLC), and such methylation is associated with a poor clinical outcome. To determine whether DAP kinase promoter methylation contributes to TRAIL resistance in NSCLC cells, we measured DAP kinase promoter methylation and its gene expression status in 11 NSCLC cell lines and correlated the methylation/expression status with the sensitivity of cells to TRAIL. Of the 11 cell lines, 1 had a completely methylated DAP kinase promoter and no detectable DAP kinase expression, 4 exhibited partial promoter methylation and substantially decreased gene expression, and the other 6 cell lines showed no methylation in the promoter and normal DAP kinase expression. Therefore, the amount of DAP kinase expression amount was negatively correlated to its promoter methylation (r = −0.77; P = 0.003). Interestingly, the cell lines without the DAP kinase promoter methylation underwent substantial apoptosis even in the low doses of TRAIL, whereas those with DAP kinase promoter methylation were resistant to the treatment. The resistance to TRAIL was reciprocally correlated to DAP kinase expression in 10 of the 11 cell lines at 10 ng/mL concentration (r = 0.91; P = 0.001). We treated cells resistant to TRAIL with 5-aza-2′-deoxycytidine, a demethylating reagent, and found that these cells expressed DAP kinase and became sensitive to TRAIL. These results suggest that DAP kinase is involved in TRAIL-mediated cell apoptosis and that a demethylating agent may have a role in enhancing TRAIL-mediated apoptosis in some NSCLC cells by reactivation of DAP kinase.
Vav Transformation Requires Activation of Multiple GTPases and Regulation of Gene Expression
Authors: Palmby Todd R. , Abe Karon , Karnoub Antoine E. , Der Channing J.
Published: May 2022

Although Vav can act as a guanine nucleotide exchange factor for RhoA, Rac1, and Cdc42, its transforming activity has been ascribed primarily to its ability to activate Rac1. However, because activated Vav, but not Rac-specific guanine nucleotide exchange factors, exhibits very potent focus-forming transforming activity when assayed in NIH 3T3 cells, Vav transforming activity must also involve activation of Rac-independent pathways. In this study, we determined the involvement of other Rho family proteins and their signaling pathways in Vav transformation. We found that RhoA, Rac1, and Cdc42 functions are all required for Vav transforming activity. Furthermore, we determined that Vav activation of nuclear factor-κB and the Jun NH2-terminal kinase mitogen-activated protein kinase (MAPK) is necessary for full transformation by Vav, whereas p38 MAPK does not seem to play an important role. We also determined that Vav is a weak activator of Elk-1 via a Ras- and MAPK/extracellular signal-regulated kinase kinase–dependent pathway, and this activity was essential for Vav transformation. Thus, we conclude that full Vav transforming activation is mediated by the activation of multiple small GTPases and their subsequent activation of signaling pathways that regulate changes in gene expression. Because Vav is activated by the epidermal growth factor receptor and other tyrosine kinases involved in cancer development, defining the role of aberrant Vav signaling may identify activities of receptor tyrosine kinases important for human oncogenesis.
Induction of Apoptosis by Antisense CK2 in Human Prostate Cancer Xenograft Model
Authors: Slaton Joel W. , Unger Gretchen M. , Sloper Daniel T. , Davis Alan T. , Ahmed Khalil
Published: May 2022

Protein serine/threonine kinase CK2 (formerly casein kinase 2) is a ubiquitous protein kinase that plays key roles in cell growth, proliferation, and survival. We have shown previously that its molecular down-regulation induces apoptosis in cancer cells in culture. Here, we have employed a xenograft model of prostate cancer to extend these studies to determine whether antisense CK2α evokes a similar response in vivo. A single dose of antisense CK2α oligodeoxynucleotide given directly into the PC3-LN4 xenograft tumor in nude mouse induced a dose- and time-dependent tumor cell death in vivo. The tumor was completely resolved at the higher tested dose of the antisense. Cell death was due to apoptosis and correlated with a potent down-regulation of the CK2α message and loss of CK2 from the nuclear matrix in the xenograft tissue as well as in cancer cells in culture. These observations accorded with several of the earlier studies indicating that loss of CK2 from the nuclear matrix is associated with induction of apoptosis. Comparison of the effects of antisense CK2α oligodeoxynucleotide on cancer versus normal or noncancer cells showed that the concentration of antisense CK2α that elicited extensive apoptosis in tumor cells in culture or xenograft tumors in vivo had a relatively small or minimal effect on noncancer cells in culture or on normal prostate gland subjected to orthotopic injection of antisense oligodeoxynucleotide in vivo. The basis for the difference in sensitivity of cancer versus noncancer cells to antisense CK2α is unknown at this time; however, this differential response under similar conditions of treatment may be significant in considering the potential feasibility of targeting the CK2 signal for induction of apoptosis in cancer cells in vivo. Although much further work will be needed to establish the feasibility of targeting CK2 for cancer therapy, to our knowledge, this is the first report to provide important new evidence as an initial “proof of principle” for the potential application of antisense CK2α in cancer therapy, paving the way for future detailed studies of approaches to targeting CK2 in vivo to induce cancer cell death.
Regulation of Polyamine Analogue Cytotoxicity by c-Jun in Human MDA-MB-435 Cancer Cells
Authors: Huang Yi , Keen Judith C. , Hager Erin , Smith Renee , Hacker Amy , Frydman Benjamin , Valasinas Aldonia L. , Reddy Venodhar K. , Marton Laurence J. , Casero Robert A. , Davidson Nancy E.
Published: May 2022

Several polyamine analogues have efficacy against a variety of epithelial tumor models including breast cancer. Recently, a novel class of polyamine analogues designated as oligoamines has been developed. Here, we demonstrate that several representative oligoamine compounds inhibit in vitro growth of human breast cancer MDA-MB-435 cells. The activator protein-1 (AP-1) transcriptional factor family members, c-Jun and c-Fos, are up-regulated by oligoamines in MDA-MB-435 cells, suggesting a possible AP-1-dependent induction of apoptosis. However, the use of a novel c-Jun NH2-terminal kinase (JNK) inhibitor, SP600125, suggests that inhibition of c-Jun activity sensitized tumor cells to oligoamine-induced cell death. To directly test this hypothesis, cells were stably transfected with the dominant-negative mutant c-Jun (TAM67), which lacks the NH2-terminal transactivation domain. Cells overexpressing TAM67 exhibit normal growth kinetics but demonstrate a significantly increased sensitivity to oligoamine cytotoxicity and attenuated colony formation after oligoamine treatment. Furthermore, oligoamine treatment leads to more profound caspase-3 activation and poly(ADP-ribose) polymerase cleavage in TAM67 transfectants, suggesting that c-Jun acts as an antiapoptosis factor in MDA-MB-435 cells in response to oligoamine treatment. These findings indicate that oligoamine-inducible AP-1 plays a prosurvival role in oligoamine-treated MDA-MB-435 cells and that JNK/AP-1 might be a potential target for enhancing the therapeutic efficacy of polyamine analogues in human breast cancer.
Mdm2 in the Response to Radiation
Authors: Perry Mary Ellen
Published: May 2022

Murine double minute 2 (Mdm2) is a critical component of the responses to both ionizing and UV radiation. The level of Mdm2 expression determines the extent to which radiation induces an increase in the activity of the p53 tumor suppressor. Mdm2 acts as a survival factor in many cell types by limiting the apoptotic function of p53. In addition, expression of mdm2 is induced in response to DNA damage, and the resulting high levels of Mdm2 protein are thought to shorten the length of the cell cycle arrest established by p53 in the radiation response. Increased levels of Mdm2 appear to ensure that the activity of p53 returns to its low basal levels in surviving cells. Decreased levels of Mdm2 sensitize cells to ionizing radiation. Thus, Mdm2 is a potential target for therapeutic intervention because its inhibition may radiosensitize the subset of human tumors expressing wild-type p53 such that radiotherapy is more efficacious.
Gastrointestinal Complications of Intra-Abdominal Desmoid Tumors: A Case Report and Review of the Literature
Authors: Morris Darcy , Gonzalez Raquel , Cook Jane , Metts Jonathan , Shaw Peter
Published: May 2022

A 15-year-old male with a mesenteric desmoid tumor and underlying familial adenomatous polyposis presented 2 weeks after initiating sorafenib with severe abdominal pain and chills and was found to have an acute abdomen. Exploratory laparotomy revealed a necrotic, ruptured tumor with impending small bowel obstruction. The patient was later able to resume sorafenib and experienced sustained a radiographic response. It is possible that sorafenib toxicity contributed to tumor rupture yet later provided clinical benefit. Here we review the gastrointestinal complications that are associated with intra-abdominal desmoid tumors and their therapies.
Low-Dose MST-16/VP-16 Combination Chemotherapy in 9 Patients with Tumor Stage Mycosis Fungoides
Authors: Kato Yukihiko , Fukuhara Yui , Nagatani Tetsuo , Kanzaki Ayano , Mae Ken-Ichiro , Irisawa Ryokichi , Harada Kazutoshi , Umebayashi Yosihiro , Tsuboi Ryoji
Published: May 2022

Background/Aim: MST-16 and VP-16, both of which are topoisomerase II inhibitors, are antitumor agents regularly used to treat malignant lymphoma and small cell lung carcinoma. New therapeutic agents for tumor stage mycosis fungoides (MF) have recently been developed, but their efficacy is limited. We herein retrospectively reported the use of MST-16/VP-16 combination therapy for tumor stage MF at multiple treatment centers and examined their antitumor effect. Methods: Five male and four female patients with tumor stage MF were enrolled. Age at the start of therapy ranged from 33 to 80 years (average: 54.5 years), and the previous treatment consisted of R-CHOP, CAVOP-IFN, etc. The protocol for low-dose MST-16/VP-16 combination chemotherapy consisted of 800 mg MST-16 and 25 mg VP-16 administered 5 days per month. Results: Three of the 9 patients died, but two of the three fatalities were unrelated to MF. A treatment effect was seen in three and 6 patients who showed a complete response and a partial response, respectively. The 5-year and 10-year overall survival rate was 85.7% and 57.1%, respectively. Adverse reactions consisted of 4 cases of nausea and 1 case of leukopenia. Conclusion: The present study demonstrated that the response rate to MST-16/VP-16 combination therapy was 100% and that the treatment effect was relatively long, suggesting that this therapy may be a viable option for treating tumor stage MF.
Bilaterales Makulaforamen: Ist eine Früherkennung möglich?
Authors: Al-Nawaiseh Sami
Published: May 2022

Background: To investigate the risk of primary macular hole (MH) in the fellow eye, and to evaluate baseline characteristics and optical coherence tomography (OCT) features that precede MH formation in the fellow eye. Methods: A retrospective review of 229 patients treated for primary MH at Stavanger University Hospital, Norway, from January 2008 through December 2018. The patients were categorised into two groups according to subsequent development of MH in the fellow eye. The OCT findings of the two groups were compared, and associated risk factors for MH formation assessed. Results: Twenty cases of bilateral MH were identified. The overall bilateral disease risk was 8.8% (95% CI, 5.8–13.2%). Two patients were previously operated in the fellow eye, six patients presented with bilateral MH, and 12 patients subsequently developed MH in the fellow eye. The risk of subsequent MH development was 5.7% (95% CI, 3.3–9.8%). Although the extent of posterior vitreous detachment (PVD) tended to be more progressed in the bilateral group compared with the unilateral group, the difference was not statistically significant. In the bilateral group, 41.7% had outer reti­nal defects vs 6.6% in the unilateral group (p = 0.001), and 33.3% in the bilateral group had intraretinal pseudocysts vs 10.2% in the unilateral group (p = 0.036, not significant after multiple testing correction). Conclusion: Outer retinal defects and intraretinal pseudocysts are associated with an increased risk of MH formation in the fellow eye, and complete PVD indicates a decreased risk of MH formation.
Aus den Augen aus dem Sinn? Die Bedeutung der Vortexvenen
Authors: Feltgen Nicolas
Published: May 2022

Die Vortexvenen sind die wichtigsten Drainagekanäle der Aderhaut. Dieser Übersichtsartikel beschreibt die Anatomie der Venen sowie Krankheitsbilder, die Anomalien hervorrufen können. Ebenso wird auf Fortschritte bei der Bildgebung der Vortexvenen eingegangen, wie z.B. die Ultraweitwinkel-Indocyaningrün-Angiographie. Ebenfalls diskutiert werden mögliche zukünftige Anwendungen der Bildgebung zum besseren Verständnis der Rolle der Vortexvenen bei retinochoroidalen Erkrankungen.
Do Patients with Psoriatic Arthritis Have More Severe Skin Disease than Patients with Psoriasis Only? A Systematic Review and Meta-Analysis
Authors: Pouw Juliëtte N. , Jacobs Marleen E. , Balak Deepak M.W. , van Laar Jacob M. , Welsing Paco M.J. , Leijten Emmerik F.A.
Published: May 2022

Background: Early identification of patients at risk of psoriatic arthritis (PsA) is essential to facilitate early diagnosis and improve clinical outcomes. Severe cutaneous psoriasis has been proposed to be associated with PsA, but a recent assessment of the evidence is lacking. Therefore, in this systematic review, we address the association of psoriasis skin severity with the presence and development of PsA. Summary: We included articles from a review published in 2014 and supplemented these with recent literature by performing an additional systematic search to identify studies published between 1 January 2013 and 11 February 2021. A meta-analysis was performed when sufficient comparable evidence was available. Of 2,000 screened articles, we included 29 in the analysis, of which 16 were identified by our updated search. Nineteen studies reported psoriasis severity as psoriasis area and severity index (PASI), ten studies as body surface area (BSA), and two studies as “number of affected sites.” Most studies show that more extensive skin disease is associated with the presence of PsA. The quantitative pooled analyses demonstrate higher PASI (mean difference [Δ] 1.59; 95% confidence interval [CI] 0.29–2.89) and higher BSA (Δ 5.31; 95% CI 1.78–8.83) in patients with PsA as compared to psoriasis patients without PsA. Results from prospective studies – that assess the risk of future development of PsA in psoriasis patients – were inconclusive. Key Messages: In patients with psoriasis, more severe skin involvement is associated with the presence of PsA, underpinning the importance of optimal dermatology-rheumatology collaboration in clinical care. There are insufficient data to support the use of psoriasis skin severity to predict the future development of PsA in psoriasis patients.
“Emergency Room Evaluation and Recommendations” and Incident Hospital Admissions in Older People with Major Neurocognitive Disorders Visiting Emergency Department: Results of an Experimental Study
Authors: Beauchet Olivier , Afilalo Marc , Allali Gilles , Lubov Joshua , Galery Kevin , Launay Cyrille P.
Published: May 2022

Introduction: Older people with major neurocognitive disorders (MNCDs) visiting the emergency department (ED) are at high risk of hospital admissions. The “Emergency Room Evaluation and Recommendations” (ER2) tool decreases the length of stay (LOS) in the hospital when older people visiting ED are hospitalized after an index ED visit, regardless of their cognitive status. Its effect on hospital admissions has not yet been examined in older people with MNCD visiting ED. This study aimed to examine whether ER2 recommendations were associated with incident hospital admissions and LOS in ED in older people with MNCD visiting ED. Methods: A total of 356 older people with MNCD visiting ED of the Jewish General Hospital (Montreal, Quebec, Canada) were recruited in this non-randomized, pre-post-intervention, single arm, prospective and longitudinal open label trial. ED staff and patients were blinded of the ER2 score, and patients received usual ED care during the observation period, whereas ED staff were informed about the ER2 score, and patients had ER2 tailor-made recommendations in addition to usual care during the intervention period. Hospital admissions and the LOS in ED were the outcomes. Results: There were less incident hospital admissions (odds ratio ≤ 0.61 with p ≤ 0.022) and longer LOS in ED (coefficient beta ≥4.28 with p ≤ 0.008) during the intervention period compared to the observation period. Discussion/Conclusion: ER2 recommendations have mixed effects in people with MNCD visiting ED. They were associated with reduced incident hospital admissions and increased LOS in ED, suggesting that they may have benefits in addition to usual ED care.
The Prognostic Significance of Chronic Kidney Disease on the All-Cause Death of Ischemic Heart Failure in the Chinese Population: A Prospective Cohort Study
Authors: Wu Zejia , Xu Lan , Cai Anping , Chen Wenzhong , Xia Shuang , He Xuyu , Qiu Weida , Xiao Xiaoju , Gao Zhiping , Chen Jiyan , Li Liwen
Published: May 2022

Objective: Our team tried to explore the impact of chronic kidney disease (CKD) on all-cause death among ischemic heart failure (IHF) patients. Methods: From December 2015 to June 2019, IHF patients were continuously recruited in the Department of Cardiology, Guangdong Provincial People’s Hospital. Participants were tracked through telephone interviews until October 15, 2020, or until the clinical endpoints appeared. The clinical endpoints were defined as all-cause death. The date of death or the last follow-up date minus the discharge date was used to calculate the follow-up time. Results: A total of 1568 IHF patients (mean age 63.5 ± 11.0 years old, 85.8% male) were included in this study. Using the estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73 m2 as the dividing line, IHF patients were divided into non-CKD group (n = 1,134) and CKD group (n = 434). After a median follow-up of 2.1 years, the all-cause death of non-CKD and CKD patients was 6.1/100 person-years and 13.7/100 person-years, respectively, and the incidence rate ratio was 2.24 (95% CI: 1.75–2.88; p value <0.001). The cumulative all-cause death of non-CKD and CKD patients were 19.4% and 40.7%, respectively (p value <0.001). CKD was an independent predictor of all-cause death in IHF patients (HR: 1.35, 95% CI: 1.03–1.76, p value = 0.029). Among IHF patients, in 8 subgroups, the all-cause death of CKD patients was consistently higher than that of non-CKD patients. Among IHF patients, the risk of all-cause death gradually increased when eGFR gradually decreased. Conclusion: Among IHF patients, CKD is a significant risk factor for all-cause death.
Estar no e com o mundo: contribuições de Freire para um jornalismo transformador
Authors: Montipó Criselli Maria , Ijuim Jorge Kanehide
Published: May 2022

Se o jornalismo está comprometido com a transformação da sociedade, tal responsabilidade fica ainda mais evidente diante das múltiplas crises vividas em nosso país – sanitária, social, política e ambiental –, que acentuam a exclusão de grande parte da população. Nesse contexto, indagamos: o jornalismo tem a potência para evidenciar as desigualdades cada vez mais agravadas e contribuir para a transformação social? Que jornalismo(s) pode(m) desempenhar esta aspiração? Neste ensaio, apoiado no pensamento de Paulo Freire e nas teorias do jornalismo, apresentamos reflexões em torno das noções de práxis jornalística, jornalistas como sujeitos conscientes e o compromisso profissional com a sociedade. Assim, argumentamos que o jornalismo aqui pretendido pode ser desempenhado por profissionais que não apenas estão no mundo, mas com o mundo.
Abstract 11: Impact Of Health Questionnaires As A Motivation Tool In African American Hypertensive Patients
Authors: Patel Dev , Patel Niraj , Patel Sunil
Published: May 2022

Hypertension is highly prevalent in African American patients with a greater incidence of cardiovascular and renal complications of hypertension as compared to other ethnic groups. However, data is sparse on positive behavioral modifiers that can help lower hypertension.

Purpose:
To evaluate the effects of a hypertension survey on patients’ self-management and self-awareness.

Method:
In an urban outpatient clinic, a prospective randomized study was conducted in African American patients with controlled hypertension. Patients were randomly assigned to survey and control (no survey) groups and were followed up 3-6 months later. The survey included demographic information, weight, number of hypertension medications, self blood pressure (BP) monitoring, hypertension complication awareness, exercise frequency, and salt intake.

Results:
There were 117 respondents in the survey and control group. In the survey group, 54% (63 of 117) were males with an average age of 57 years. Average BP was 125/79 mm hg vs 127/80 mm hg post survey. On follow up average BMI decreased (35.1 vs 32.9, p = 0.038), self BP monitoring increased (25.6% vs 81.1% [30 vs 95 of 117, p < 0.005]), low salt diet intake increased (32% vs 60% [38 vs 71 of 117, p = 0.016]), exercise frequency 3-5 days/week increased (29% to 49% [34 vs 58 of 117, p = 0.028]), awareness of hypertensive complication improved (15% vs 74% [18 vs 87 of 117, p < 0.005]), and BP control without medication increased (4.3% vs 10.2% [5 vs 12 of 117, p = 0.046]). In the control group, 58% (67 of 117) were males with an average age of 56 years. Average BP was 126/80 vs 125/72 post survey. On follow up average BMI decreased (34.3 vs 33.8, p = 0.809), self BP monitoring increased from (28.2% vs 35% [33 vs 41of 117, p = 0.582]), Low salt diet intake increased (30% vs 36% [36 vs 43 of 117, p = 0.773 ]), exercise frequency 3-5 days/week decreased (31% to 24% [36 vs 29 of 117]), awareness of hypertensive complication improved (16% vs 23% [19 vs 28 of 11, p = 0.682]), and BP control without medication decreased (5.1% vs 1.7% [6 vs 2 of 117]).

Conclusion:
Our study suggests the action of completing a survey served as a positive behavioral and self-awareness modifier. The survey group showed a higher incidence of positive change compared to the control group.
Abstract 155: Gender Differences In Patients With Ventricular Arrhythmias Undergoing Catheter Ablation
Authors: Algarate Percy T , Chagari Krithika , Giedrimiene Dalia , Kluger Jeffrey
Published: May 2022

Significant differences in the clinical presentation and outcomes of cardiovascular diseases in men and woman have been described in the last few decades, including in management of cardiac arrhythmias. Recently, catheter ablation for ventricular arrhythmia (VA) has been shown to be highly effective at reducing ventricular tachycardia (VT) and premature ventricular contractions (PVC) burden, including reduction of VA episodes. Much of the published data has identified risk factors for VA recurrence, such as low LVEF, but have not included enough women for meaningful comparison of gender-based differences. The goal of this study was to examine gender differences in patients with ventricular arrhythmias who have undergone VA ablation. We conducted a retrospective analysis on a cohort of 115 patients receiving VA ablation at a tertiary hospital (54 pts for VT and 63 pts for PVC, 76 males and 39 females) to identify gender differences in patient characteristics at time of ablation. In the total group, there were 76 (66.1% males and 39 (33.9%) females, mean age - 59.6 +14.8 years; av. LVEF = 46.6% + 13.63%). Females were younger (52.2 vs 63.9 years) and had higher LVEF (53.7% vs 43.1%) as compared to men. History of pre-procedure ICD, ischemic heart disease and procedures, such as CABG or stent placement, were higher in men. Also, more males were diagnosed with hypertension and dyslipidemia. VT patients had lower LVEF and a higher proportion of males with worse pre-procedure characteristics than PVC patients. Hypertension and older age were observed among males in both PVC and VT groups. Overall, study results show female patients had less severe comorbidities, younger age and better LVEF. These findings can reflect differences in VA ablation outcomes as well as the selection of treatments for patients with VA.
Abstract 156: Insights From Meta-analysis Of Studies Using Machine Learning To Predict Mortality, Readmission, Or Other Outcomes Among Heart Failure Patients
Authors: Zhang Zhenwei , Ahmed Md Ashfaq , McGranaghan Peter , Rubens Muni , Ramamoorthy Venkataraghavan , Saxena Anshul , Chaparro Sandra , Jimenez Javier , Veledar Emir
Published: May 2022

Developing and implementing analytical models for predicting mortality or readmission related outcomes among heart failure (HF) patients are challenging. In this study, we used meta-analyses of reported predictive models to assess what machine learning (ML) has been able to accomplish in this field, by evaluating the ML model performance for studies in HF.

We performed a literature search using Google Scholar, Web of Science and PubMed. The studies reporting AUC and 95% CI for various models were included. In addition, total participants, year of publication, type of analytical method (logistic regression, RF, etc.) and type of outcome (mortality, readmission, etc.) were extracted. We combined effect sizes using random effects (RF) model, and tested for heterogeneity, and publication bias.

12 studies were included in the analysis (patients= 123,832; AUC=15, with outcome mortality =17,471, readmission=15,703, hospitalization=67,523). Combined mean AUC was 0.77 (95% CI: 0.72, 0.82). Test of heterogeneity showed high variation between studies (I2=98.9%). Egger’s test intercept was 5.2 (95% CI: -4.2, 14.7, p > .25) indicating no small study effects/bias. Meta regression showed newer publications provide better AUC values (p < 0.03). In subgroup analysis, the pooled AUC for readmission, hospitalization, and mortality groups were 0.71, 0.80, and 0.78 respectively. The highest individual AUC was from neural networks (NN) predicting hospitalization with AUC 0.96 and lowest was from RF predicting readmission with AUC 0.65.

Presented models were diverse, ranking in quality from fair to very good, and being varied for different clinical outcomes among HF patients. Situation known from studies using classical statistical methods holds also for methods using ML, with better predictive values for hospitalizations, and lower for other outcomes. Methods using NN and methods using higher numbers of variables performed very well and had highest predictive power.
Abstract 159: Understanding Baseline Physical Activity In Cardiac Rehabilitation Enrollees Using Mobile Health Technologies
Authors: Golbus Jessica R , Gupta Kashvi , Stevens Rachel , Jeganathan V. Swetha , Luff Evan , Kohnstamm Sarah , Nallamothu Brahmajee K
Published: May 2022

Background:
Cardiac rehabilitation (CR) improves physical activity (PA) and reduces morbidity for patients with cardiovascular disease. We understand little of baseline PA as patients initiate CR, particularly when outside of CR. We used mobile health (mHealth) technology to understand baseline PA of patients initiating CR within a clinical trial to potentially inform personalized care.

Methods:
The Virtual AppLication-Supported Environment to INcrease Exercise During Cardiac Rehabilitation Study (VALENTINE) Study is a prospective, randomized-controlled, remotely administered trial designed to evaluate an mHealth intervention to supplement CR for low- and moderate-risk patients. Participants are randomized after 2 CR sessions; all receive a smartwatch and usual care. Remotely administered baseline PA outcomes include 6-minute walk distance, step count, and exercise minutes. Baseline PA was assessed for 7-days after study enrollment for compliant days, defined by
>
8 hours of watch wear/day. Multivariable linear regression identified features associated with baseline PA.

Results:
From October 19, 2020 to January 31, 2022, 180 participants enrolled. Participants are mostly White [156 (86.7%)]; 59 (32.8%) are female and 69 (38.3%) are
>
65 years old. Most enrolled in CR after coronary revascularization [114 (64.4%)] or valve intervention [40 (22.2%)]. Comorbidities include hypertension (65.0%), valve disease (35.6%), and heart failure (17.8%). Participants were compliant for 91.4% of days with 15.3 (4.0) hours/compliant day. Baseline PA included 6-minute walk distance of 491.8 (147.8) meters, daily step count of 6818 (3386), and exercise minutes of 36.0 (33.4). Substantial variation in baseline PA assessed by 6-minute walk distance was noted across age and gender but not CR indication.

Conclusions:
Understanding baseline PA as participants enroll in CR may be useful in personalizing CR programs at initiation and designing mHealth interventions.
Abstract 160: Nurse Driven Protocol For Medication Routes In Adult Patients With Pharmacy Assistance
Authors: Barnett Anna Claire , Daniels Carmelita C , San Juan Vinna Patricia , Dawson Kelsey
Published: May 2022

Introduction/ Objective:
Stroke patients are at high risk for swallowing complications which leads many patients to receive a temporary or permanent enteral feeding tube. Providers are required by regulatory guidelines to indicate in medication orders the specific route in which a medication will be administered. The data for our stroke patients from CY (calendar year) 2020 showed a 23% average of stroke patients had incorrectly documented medication routes. We designed a pilot study to assess the feasibility of a nurse driven protocol that involved nursing communication with pharmacy to change medication routes. This protocol was created to ensure safe and timely administration, correct medication dosage and formulation, and would meet standards of regulatory guidelines for medication orders.

Methods:
All patients admitted to the neurosurgical ICU were included in the pilot from April 5
th
to May 3
rd
, 2021. In the pilot, nursing had the ability to enter a “substitute dosage form” through the existing medication request system in the electronic medical record (MedConnect). This MedConnect request alerted the Pharmacist to review all medications on the MAR and change the administration routes to the correct route as indicated by the nurse on the request. After review, the pharmacist would contact the provider for either an order discontinuation or a new order for medications identified as unable to be crushed or requiring a new order for appropriate formulation conversion.

Results:
During the pilot study period a total of 102 patients were admitted to the neurosurgical ICU. Of these patients, 15% (15/102) had medications documented with the incorrect route by the nurse. Of those 15 patients, 73% (11/15) did not have a medication request completed by the nurse. The remaining patients (4/15) or 27% had a medication request completed by a nurse but pharmacy failed to intervene. Comparing this data to that of CY 2020, there was an 8% improvement in correct medication routes.

Conclusion:
A nurse driven protocol for medication routes involving pharmacy is feasible and may be associated with a reduction of medication route errors. The plan is to expand this nurse driven protocol house-wide at our hospital.
Abstract 165: A Comparative Study Of The Continuum Of Type 2 Diabetes Mellitus Care For African Americans And Caucasians On Medicare From 2006-2016
Authors: Shetty Anand B
Published: May 2022

Introduction:
Increasing evidence is emerging supporting the disparity between African Americans (AA) and their Caucasian (C) counterparts raising great concern for the equity of quality healthcare across the nation.

Purpose:
The purpose of this study was to describe the relationship between the risk factors, complications, and interventions associated with Diabetes Mellitus in the African American and Caucasian populations in the United States between 2006-2016.

Methods:
Data was obtained from the Center for Medicaid and Medicare for the Diabetes Mellitus population from 2006-2016.

Results:
Based on this study, AA required more hospital visits, sustained more limb amputations, had a higher population diagnosed with hypertension, and displayed decreased utilization of physical therapy in each of the three-year ranges. No significant changes are seen when looking at the number of hospital visits from 2006-2016 in both races. Lower limb amputation also shows minor changes over the year ranges, with C increasing slightly from 2009-2011 to 2012-2016 and AA gradually decreasing from 2006-2008 to 2009-2011 and again from 2009-2011 to 2012-2016. A reduction in patients diagnosed with hypertension in both C and AA is seen when comparing 2006-2008 to 2009-2011 and again when comparing 2009-2011 to 2012-2016. Number of physical therapy visits increased in both races from 2006-2016 which in turn is shown by the percentage of both races not utilizing PT decreasing from 2006-2016. African Americans displayed higher rates of complications and less access to healthcare treatment when compared to the population of Caucasians. When comparing year spans, the results varied between each complication but overall, decreasing trends were seen in favor of better healthcare access and outcomes.

Discussion/Conclusion:
. From this study, it can be reasonably concluded that there are disparities in the primary and secondary care of African Americans when compared to Caucasians.

Table