bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic Drug Monitoring to Guide Clinical Decision Making in Inflammatory Bowel Disease Patients with Loss of Response to Anti-TNF: A Delphi Technique-Based Consensus
Authors: Greuter Thomas , Maillard Michel H. , Juillerat Pascal , Michetti Pierre , Seibold Frank , Mottet Christian , Zahnd Nadine , Sauter Bernhard , Schoepfer Alain M. , Rogler Gerhard , Vavricka Stephan R. ,   on behalf of the Swiss IBDnet, an official working group of the Swiss Society of Gastroenterology
Published: September 2019

Background: Loss of response is frequently encountered in patients with inflammatory bowel disease (IBD) treated with antitumor necrosis factor (TNF) agents. Therapeutic drug monitoring (TDM) and antidrug antibody measurement are increasingly used in this setting. Methods: To establish a consensus on the use of TDM in the context of loss of response to anti-TNFs, we performed a vote using a Delphi-style process followed by an expert panel discussion among 8 IBD specialists practicing in Switzerland, Europe. Statements were rated on an even Likert-scale ranging from 1 (strong disagreement) to 4 (strong agreement), based on expert opinion and the available literature. Results: The experts agreed on the following statements: (i) loss of response is associated with inadequate drug levels in both Crohn’s disease and ulcerative colitis; (ii) best timepoint for measuring drug levels is prior to the next application (= trough levels) with different thresholds for anti-TNF agents (infliximab 5 μg/mL, adalimumab 8 μg/mL, certolizumab pegol 10 μg/mL); (iii) antidrug antibodies are predictive for loss of response; and (iv) antidrug-antibody titers and drug trough levels are key determinants in the treatment algorithm. Data about non-anti-TNF biologics were considered too limited to propose recommendations. Conclusion: A Delphi-style consensus among 8 IBD experts shows that TDM and measurement of antidrug-antibody titers are useful in the context of loss of response to anti-TNF. Optimal cutoff levels depend on the type of anti-TNF. These values are critical in the decision making process. More studies are needed to address the value of such measurements for non-anti-TNF biologics.
The Determinants of the Preferred Walking Speed in Individuals with Obesity
Authors: Fernández Menéndez Aitor , Saubade Mathieu , Hans Didier , Millet Grégoire P. , Malatesta Davide
Published: September 2019

Background: The preferred walking speed (PWS), also known as the “spontaneous” or “self-selected” walking speed, is the speed normally used during daily living activities and may represent an appropriate exercise intensity for weight reduction programs aiming to enhance a more negative energy balance. Objectives: The aim of this study was to examine, simultaneously, the energetics, mechanics, and perceived exertion determinants of PWS in individuals with obesity. Methods: Twenty-three adults with obesity (age 32.7 ± 6.8 years, body mass index 33.6 ± 2.6 kg/m2) were recruited. The participants performed 10 min of treadmill familiarization, and PWS was determined. Each subject performed six 5-min walking trials (PWS 0.56, 0.83, 1.11, 1.39, and 1.67 m/s). Gas exchanges were collected and analyzed to obtain the gross energy cost of walking (GCw), rated perceived exertion (RPE) was measured using a 6–20 Borg scale, and the external mechanical work (Wext) and the fraction of mechanical energy recovered by the pendular mechanism (Recovery) were computed using an instrumented treadmill. Second-order least-squares regression was used to calculate the optimal walking speed (OWS) of each variable. Results: No significant difference was found between PWS (1.28 ± 0.13 m/s) and OWS for GCw (1.28 ± 0.10 m/s), RPE cost of walking (1.38 ± 0.14 m/s), and Recovery (1.48 ± 0.27 m/s; p > 0.06 for all), but the PWS was significantly faster than the OWS for Wext (0.98 ± 0.56 m/s; p < 0.02). Multiple regression (r = 0.72; p = 0.003) showed that ∼52% of the variance in PWS was explained by Recovery, Wext, and height. Conclusion: The main finding of this study was that obese adults may select their PWS in function of several competing demands, since this speed simultaneously minimizes pendular energy transduction, energy cost, and perceived exertion during walking. Moreover, recovery of mechanical work, external work, and height seem to be the major determinants of PWS in these individuals.
Treatment of Moderate-to-Severe Psoriasis in the Presence of Kaposi’s Varicelliform Eruption
Authors: Campanati Anna , Molinelli Elisa , Brisigotti Valerio  , Brancorsini Donatella , Bobyr Ivan , Diotallevi Federico , Radi Giulia , Offidani Annamaria
Published: September 2019

Kaposi’s varicelliform eruption (KVE) is a disseminated cutaneous infection usually induced by herpesvirus type 1 or 2, vaccinia virus or Coxsackie A16 virus in a patient with an underlying dermatosis. Risk factors for KVE reported in the literature include erythroderma, systemic sepsis, therapy with immunosuppressants such as methotrexate and systemic steroids, and therapy with systemic retinoids. The occurrence of KVE in psoriasis is rare and it predominantly appears in patients affected by erythrodermic psoriasis during immunosuppressive treatment. We report our experience of a remarkable case of a patient affected by severe erythrodermic psoriasis and KVE that healed after antiviral treatment and after having received secukinumab. After 1 year, psoriasis was cleared and no recurrence of KVE had occurred.
Secukinumab in the Treatment of Plaque Psoriasis in Patients with Malignancy
Authors: Gambardella Alessio
Published: September 2019

Although available data are conflicting, psoriasis seems to be associated with an increased baseline risk of malignancy. In addition, some antipsoriatic systemic treatments have been associated with risk of malignancy. There is not enough data on the association of interleukin (IL)-17 and IL-23 inhibitors with malignancy rate, but there have been no cases reported so far. Secukinumab is a recombinant human monoclonal immunoglobulin G1/κ antibody that selectively targets IL-17A; it was demonstrated to be effective and safe for the treatment of moderate to severe psoriasis that may be appropriate in frail subjects, as patients previously experienced malignancy, as in the case reported.
Immediate Effect of Dry Swallowing Maneuver in Patients with Neurogenic Dysphagia
Authors: Veras Mayara Rosa , Kitani Claudia Tiemi Mituuti , Furkim Ana Maria , Luchesi Karen Fontes
Published: September 2019

Background: Compensatory deglutition strategies such as change of posture, swallowing maneuvers, and sensory stimulation have been used by speech-language pathologists (SLPs) to alter oral and pharyngeal biodynamics. Objective: To analyze the immediate effect of the dry swallowing maneuver in patients with neurogenic dysphagia. Methodology: The participants were 11 individuals with neurogenic dysphagia who underwent videofluoroscopic swallowing study while performing dry swallow maneuvers for different consistencies. The amount of pre- and post-maneuver residue was measured for the tongue base, vallecula, posterior pharyngeal wall, and pyriform sinus. Two experienced SLPs analyzed the videos blindly as to the timing, pre- or post-maneuver, and information about the videos. In cases of disagreement between the judges, a third judge broke the tie for each structure whose analysis was in disagreement. Results: There was a significant reduction of residue after dry swallowing maneuvers on the tongue and vallecula. There was no significant difference in the amount of pre- and post-maneuver residue for the posterior pharyngeal wall and pyriform sinus. The amount of pre- and post-maneuver residue showed no significant interference from the different consistencies tested. Conclusion: The dry swallowing maneuver showed an immediate improvement effect for the clearance of residues on the base of tongue and vallecula.
The Long-Noncoding RNA lnc-NONH Enhances the Early Transcription of Prototype Foamy Virus Via Upregulating Expression of miR-34c-5p and Tas Protein
Authors: Xu Shanshan , Yang Wenqiong , Yuan Peipei , Yan Jun , Tang Yinglian , Zheng Yingcheng , Li Zhi , Sun Yan , Han Song , Yin Jun , Peng Biwen , He Xiaohua , Pan Qin , Liu Wanhong
Published: September 2019

Background: Prototype foamy virus (PFV) is a complex and unique retrovirus with the longest genome among the retroviruses and is used as a vector for gene therapies. The viral Tas protein transactivates the viral long terminal repeat promoter and is required for viral replication. We have utilized RNA sequencing to identify and characterize the long-noncoding RNA NONHSAG000101 (lnc-NONH), which markedly increases in PFV-infected cells. However, little is known about the function of lnc-NONH. Objectives: We aim to explore the role of lnc-NONH during PFV infection. Methods: To assess the lnc-NONH role during PFV infection, the siRNAs were used to silence the lnc-NONH expression. The microRNA (miRNA) mimic and inhibitor were employed to explore the function of lnc-NONH-related miRNA miR-34c-5p. Quantitative real-time polymerase chain reaction assay and Western blotting were applied to measure the mRNA and protein levels of PFV transactivator Tas. Luciferase assay was used to determine the transcriptional activity of the PFV unique internal promoter (IP). Results: lnc-NONH promotes the expression of PFV Tas and miR-34c-5p. The interaction between lnc-NONH and miR-34c-5p enhances the transcriptional activity of the PFV IP. Conclusions: In the current study, we report a novel mechanism for the lnc-NONH-mediated upregulation of Tas expression. Our findings contribute to the understanding of regulatory network of Tas expression and PFV replication.
Inhibition of Euchromatic Histone Lysine Methyltransferase 2 (EHMT2) Suppresses the Proliferation and Invasion of Cervical Cancer Cells
Authors: Chen Guoqiang , Yu Xiaqing , Zhang Min , Zheng Aiwen , Wang Zhennan , Zuo Yufang , Liang Qilian , Jiang Danxian , Chen Yaqing , Zhao Lingqin , Jiang Liyuan , Li Dan , Liao Sihai
Published: September 2019

EHMT2 (euchromatic histone lysine methyltransferase 2), a histone methyltransferase, has been shown to be involved in multiple human cancers. In this study, we determined mRNA and protein expression of EHMT2 in cervical cancer cells and normal cervical epithelial cells. EHMT2 was inhibited with short hairpin RNA (shEHMT2) in cervical cancer cells. Cell viability, colony proliferation, apoptosis, adhesion, and invasion assays and Western blot were performed to assess the function of EHMT2. As a result, EHMT2 was upregulated in human cervical cancer cells compared to normal cervical epithelial cells. Suppression of EHMT2 expression impairs cell proliferation and induces apoptosis. Furthermore, EHMT2 silencing inhibited cell adhesion and invasion. Finally, knockdown of EHMT2 resulted in a reduction of the expression of the tumorigenic proteins Bcl-2, Mcl-1, and Survivin and in an increase in the expression of the anti-malignant protein E-cadherin. In conclusion, our data suggest that EHMT2 plays a key role in cell proliferation and metastatic capacity in cervical cancer cells and could serve as a potential therapeutic target.
Takotsubo Syndrome and Inflammatory Bowel Diseases: Does a Link Exist?
Authors: Mirijello Antonio , D’Errico Maria Maddalena , Curci Serafino , Bossa Fabrizio , d’Angelo Cristina , Vendemiale Gianluigi , Gasbarrini Antonio , Addolorato Giovanni , De Cosmo Salvatore
Published: September 2019

Background: Takotsubo syndrome (TTS) is an acute cardiac dysfunction in the absence of viral causes or obstructive coronary disease completely reversible within 4–8 weeks. Inflammatory bowel diseases (IBD) are a group of diseases caused by the interaction between immune system, genetic, and environmental factors against intestinal mucosa. Both these syndromes are characterized by complex mechanisms involving endothelial dysfunction and affective disorders. Aim: To assess the possibility of an association between IBD and TTS. Methods: First, we present a case of TTS in a patient affected by active stenosing Crohn’s disease. Articles in English language were collected from PubMed and Google Scholar databases with the search terms “takotsubo,” “IBD,” “crohn disease,” “ulcerative colitis”. Results: Both TTS and IBD show multiple common features: preference for female patients, recurrent course of disease, association with endothelial dysfunction, and affective disorders. Patients affected by IBD could show specific triggers for TTS, such as malabsorption, electrolytes disturbances, and affective disorders. Conclusions: Despite pathophysiological similarities between TTS and IBD in active phase, future studies are needed to confirm this apparently possible association and to assess the presence of a pathophysiological link between these diseases.
Early Relative Change in Hepatic Function with Lenvatinib for Unresectable Hepatocellular Carcinoma
Authors: Hiraoka Atsushi , Kumada Takashi , Atsukawa Masanori , Hirooka Masashi , Tsuji Kunihiko , Ishikawa Toru , Takaguchi Koichi , Kariyama Kazuya , Itobayashi Ei , Tajiri Kazuto , Shimada Noritomo , Shibata Hiroshi , Ochi Hironori , Tada Toshifumi , Toyoda Hidenori , Nouso Kazuhiro , Tsutsui Akemi , Nagano Takuya , Itokawa Norio , Hayama Korenobu , Imai Michitaka , Joko Kouji , Koizumi Yohei , Hiasa Yoichi , Michitaka Kojiro ,   On behalf of the Real-Life Practice Experts for HCC (RELPEC) Study Group and HCC 48 Group (hepatocellular carcinoma experts from 48 clinics in Japan)
Published: September 2019

Background/Aim: Lenvatinib (LEN) has been developed for the treatment of unresectable hepatocellular carcinoma (u-HCC). We aimed to elucidate the relative change in hepatic reserve function early following LEN treatment in affected patients. Materials/Methods: From March 2018 to April 2019, 123 u-HCC patients (median age 71 years; male:female ratio 95:28; Child-Pugh score 5:6:7 = 65:50:8; modified albumin-bilirubin [mALBI] grade 1:2a:2b:3 = 44:28:50:1, Barcelona Clinic Liver Cancer stage A:B:C = 1:49:73) were enrolled. Relative changes in hepatic reserve function at 2 and 4 weeks after starting LEN were retrospectively evaluated. Results: The median survival was 11.3 months. The Child-Pugh score declined from the start to 4 weeks after commencing LEN (score 5:6:7:8:9:≥10 = 65:50:8:0:0:0 vs. 50:39:22:8:0:4, p < 0.001). A comparison among ALBI scores at the start of LEN and those at 2 and 4 weeks revealed significant relative changes (–2.36 ± 0.45 to –2.20 ± 0.49 at 2 weeks, –2.15 ± 0.50 at 4 weeks, p < 0.001, Bonferroni method), while there was no significant difference between those at 2 and 4 weeks (p= 0.210, Bonferroni method). Assessments of relative changes of ALBI score in patients divided by mALBI grade 1, 2a, and 2b or more showed a significant decline in score regardless of grade (–2.82 ± 0.17 to –2.53 ± 0.34, p < 0.001; –2.46 ± 0.10 to –2.31 ± 0.33, p = 0.017; and –1.90 ± 0.26 to –1.75 ± 0.42, p= 0.009, respectively). Conclusion: Decline in hepatic function is common in the early stage (≤4 weeks, especially within 2 weeks) after introducing LEN. It is important to introduce molecular targeting agent drugs for u-HCC in patients with better hepatic function, who show transarterial catheter chemoembolization failure, as much as possible, along with consideration of the negative influence of LEN on the early response of hepatic function.
Successful Negotiation of Anticipated and Unanticipated Obstacles in Young and Older Adults: Not All Is as Expected
Authors: Eyal Shlomit , Kurz Ilan , Mirelman Anat , Maidan Inbal , Giladi Nir , Hausdorff Jeffrey M.
Published: September 2019

Background: Tripping over an obstacle is one of the most common causes of falls among older adults; however, the impact of obstacle parameters and subject characteristics are not well described. Objectives: To evaluate age-associated changes in the ability to negotiate obstacles and the role of obstacle parameters (e.g., anticipated vs. unanticipated, height, and available response time [ART]), and subject characteristics. Methods: Twenty healthy older adults (77.7 ± 3.4 years; 50% women) and 20 healthy young adults (29.3 ± 3.8 years; 50% women) underwent cognitive, gait, and balance testing before negotiating a computer-controlled obstacle course. The primary outcome measure was the ability to successfully negotiate the obstacles (without touching them). Results: The success rate for all subjects was higher when the obstacle was anticipated (99.0 ± 2.8%) than when unanticipated (66.0 ± 20.2%; p < 0.001). The obstacle height had a significant effect on the success rate (p = 0.022); the success rate was lower when the obstacle height was lower. No significant interaction between group and obstacle height was observed (p = 0.096). ART had no significant effect on the success rate (p = 0.294) in both of the groups (ART × group, p = 0.136). However, a significant interaction between group, obstacle height, and ART was found (p = 0.013), reflecting a lower success rate in the older adults when the obstacles were low and unanticipated. In general, older adults demonstrated a trend towards a lower success rate in all types of obstacles compared to the young adults (p = 0.057). Among the older adults, the success rate in the anticipated obstacle condition was correlated with stride length (ρ = 0.600, p = 0.005), step time coefficient of variation (ρ = –0.635, p = 0.003), and gait speed (rho = 0.530, p = 0.016). Montreal Cognitive Assessment scores tended to be related to the difference in the success rate between the anticipated and unanticipated conditions. Conclusions: These findings support the idea that motor and, to some degree, cognitive functions are needed to successfully negotiate obstacles, and provide new insights into the ability of older adults to successfully negotiate obstacles. Furthermore, the present results suggest that when it comes to the physical properties of obstacles, not all is as expected, and low obstacles may impose a greater danger to tripping than obstacles that have a higher height.
Tofacitinib as Induction and Maintenance Therapy in Japanese Patients with Active Ulcerative Colitis
Authors: Suzuki Yasuo , Watanabe Mamoru , Matsui Toshiyuki , Motoya Satoshi , Hisamatsu Tadakazu , Yuasa Hirotoshi , Tabira Junichi , Isogawa Naoki , Tsuchiwata Shinichi , Arai Shoko , Hibi Toshifumi
Published: September 2019

Background: Tofacitinib is an oral, small molecule Janus kinase inhibitor approved in Japan for the treatment of ulcerative colitis (UC). Differences in the safety profile of tofacitinib in Japanese patients versus the global population, such as a higher risk of herpes zoster, have been reported. Objectives: We conducted post hoc analyses of tofacitinib treatment in Japanese patients with moderate-to-severe UC in two global phase III studies. Methods: In OCTAVE Induction 1 (NCT01465763), 62 patients were randomized to placebo or tofacitinib 10 mg twice daily (b.i.d.). In OCTAVE Sustain (NCT01458574), 39 patients with clinical response in OCTAVE Induction 1 were re-randomized to placebo, tofacitinib 5 mg, or 10 mg b.i.d. Efficacy endpoints included: remission (primary endpoint; total Mayo score ≤2; no individual subscore >1; rectal bleeding subscore 0); mucosal healing (Mayo endoscopic subscore ≤1); clinical response (≥30% and ≥3-point decrease from induction study baseline total Mayo score; decrease in rectal bleeding subscore ≥1 or absolute subscore ≤1). Adverse events (AEs) and clinical laboratory parameters were recorded. Results: At week 8 of OCTAVE Induction 1, 22.4% of patients achieved remission with tofacitinib (placebo, 7.7%). At week 52 of OCTAVE Sustain, 31.3% and 66.7% of patients receiving tofacitinib 5 and 10 mg b.i.d., respectively, achieved remission (placebo, 9.1%). The occurrence of AEs or serious AEs in Japanese patients was generally similar to that in the global study population, with no new or unexpected safety risks observed. Conclusions: Although patient numbers were small, tofacitinib demonstrated numerically greater efficacy versus placebo among Japanese patients in OCTAVE Induction 1 and OCTAVE Sustain, with a safety profile consistent with that of the global study population.
Identification of Factors Associated with Postoperative Urosepsis after Ureteroscopy with Holmium: Yttrium-Aluminum-Garnet Laser Lithotripsy
Authors: Bai Tao , Yu Xi , Qin Cong , Xu Tao , Shen Hao , Wang Lei , Liu Xiuheng
Published: September 2019

Objective: To report the incidence and risk factors of urosepsis after ureteroscopic lithotripsy (URSL). Patients and Methods: We retrospectively reviewed 1,421 patients who underwent URSL for ureteral calculi between July 2015 and June 2018 at our department to identify factors predicting postoperative urosepsis. Demographic characteristics, clinical data, operative information, and complications were compared, and risk factors of postoperative urosepsis were identified and analyzed. Results: Of the 1,421 patients treated with URSL using holmium: yttrium-aluminum-garnet laser, 12 (0.8%) developed a urosepsis after operation. The positive preoperative multidrug resistance (MDR) urine culture and operative duration were statistically different between those who did and did not develop a urosepsis (4.61 vs. 25%, p = 0.017; 70 vs. 62 min, p < 0.001). However, patient age, sex, body mass index, diabetes mellitus, history of urolithiasis, positive preoperative urine cultures, stone size and location, degree of hydronephrosis, and prior stent placement were similar in 2 groups. Multivariate analysis revealed that positive preoperative MDR urine culture and long operation duration significantly increased the risk of postoperative urosepsis (OR 5.090, 95% CI 1.312–19.751, p = 0.019; OR 1.034, 95% CI 1.004–1.063; p = 0.024). Matched-pair analysis demonstrated that positive preoperative MDR urine culture and operation duration were significantly associated with postoperative urosepsis (OR 15.77, 95% CI 1.033–240.7, p = 0.047; OR 1.087, 95% CI 1.011–1.169, p = 0.025). Conclusions: Patients with positive preoperative MDR urine culture or long operation duration had a higher risk of developing urosepsis after URSL. When treating patients who present with positive preoperative MDR urine culture or long operation duration, urologists should be vigilant and aware of the potential risk of urosepsis.
Stroke Factors Associated with Thrombolysis Use in Hospitals in Singapore and US: A Cross-Registry Comparative Study
Authors: Ng Sheryl Hui-Xian , Wong Alex W.K. , Chen Cynthia Huijun , Tan Chuen Seng , Müller-Riemenschneider Falk , Chan Bernard P.L. , Baum M. Carolyn , Lee Jin-Moo , Venketasubramanian Narayanaswamy , Koh Gerald Choon-Huat
Published: September 2019

Background and Objectives: This paper aims to describe and compare the characteristics of 2 stroke populations in Singapore and in St. Louis, USA, and to document thrombolysis rates and contrast factors associated with its uptake in both populations. Methods: The stroke populations described were from the Singapore Stroke Registry (SSR) in ­Singapore and the Cognitive Rehabilitation Research Group Stroke Registry (CRRGSR) in St. Louis, MO, USA. The registries were compared in terms of demographics and stroke risk factor history. Logistic regression was used to determine factors associated with thrombolysis uptake. Results: A total of 39,323 and 8,106 episodes were recorded in SSR and CRRGSR, respectively, from 2005 to 2012. Compared to CRRGSR, patients in SSR were older, male, and from the ethnic majority. Thrombolysis rates in SSR and CRRGSR were 2.5 and 8.2%, respectively, for the study period. History of ischemic heart disease or atrial fibrillation was associated with increased uptake in both populations, while history of stroke was associated with lower uptake. For SSR, younger age and males were associated with increased uptake, while having a history of smoking or diabetes was associated with decreased uptake. For CRRGSR, ethnic minority status was associated with decreased uptake. Conclusions: The comparison of stroke populations in Singapore and St Louis revealed distinct differences in clinicodemographics of the 2 groups. Thrombolysis uptake was driven by nonethnicity demographics in Singapore. Ethnicity was the only demographic driver of uptake in the CRRGSR population, highlighting the need to target ethnic minorities in increasing access to thrombolysis.
The Effects of Listening to Music on Anxiety, Pain, and Satisfaction during Urodynamic Study: A Randomized Controlled Trial
Authors: Diri Mehmet Akif , Çetinkaya Funda , Gül Murat
Published: September 2019

Introduction: To assess the influence of music therapy on perceived anxiety and pain during outpatient urodynamic study (UDS) in a prospective, randomized fashion. Methods: Between January and December 2018, a total of 70 patients were randomized to either have music therapy (study) or not have (control) in a 1:1 ratio. To the study group, Sufi music was delivered at low tempo. All participants performed the State-Trait Anxiety Inventory evaluation after the procedure and assessed their degree of pain, satisfaction, and willingness to undergo an additional or repeat procedure using the Visual Analog Scale. Results: Patient demographic and baseline characteristics were found to be similar between the 2 groups. Though music did not significantly alleviate pain (4.6 ± 1.2 vs. 4.4 ± 1.7; p = 0.76) and anxiety (47.7 ± 7.75 vs. 46.4 ± 6.5; p = 0.36), it had a positive impact on the patient’s willingness to repeat UDS (3.4 ± 1.4 vs. 6.1 ± 1.3; p = 0.005) and provided overall satisfaction (4.6 ± 0.61 vs. 7.2 ± 1.33; p = 0.004). Conclusions: Music is a practical, harmless, and inexpensive non-pharmacological option that can be adopted during medical and surgical procedures, although according to this present study, listening to music during UDS had no effect on pain and anxiety levels.
Enhanced Renal Vascular Responsiveness to Angiotensin II and Norepinephrine: A Unique Feature of Female Rats with Congestive Heart Failure
Authors: Krátký Vojtěch , Kikerlová Soňa , Husková Zuzana , Sadowski Janusz , Kolář František , Červenka Luděk
Published: September 2019

Background/Aims: We found recently that the aortocaval fistula (ACF)-induced heart failure (HF) results in higher mortality in female than in male rats. Possibly, the development of renal dysfunction in the females, unlike in males, is associated with altered renal vascular responsiveness to angiotensin II (ANG II). Methods: Five or 20 weeks after ACF creation (compensated and decompensated HF, respectively), we assessed renal blood flow (RBF) responses to intrarenal administration of ANG II, norepinephrine (NE), and acetylcholine (Ach) in female ACF and sham-operated rats. Results: In ACF females, ANG II decreased RBF more than in healthy animals, unlike with earlier published data in male ACF rats that responded similarly. Also, NE decreased RBF more in female ACF rats, whereas Ach increased RBF to the same extent in female ACF and sham-operated rats. RBF responses to intravenous administration of NE and Ach were almost identical in female and male ACF rats. Conclusion: Female ACF rats studied at the onset of HF decompensation reveal, in contrast to male rats, enhanced renal vascular responsiveness to both NE and ANG II. When associated with the demonstrated increased intrarenal ANG II and NE concentrations, such hyperresponsiveness might promote the development of renal dysfunction and accelerate HF decompensation.
Mechanisms of Stroke in Patients with Chronic Kidney Disease
Authors: Ghoshal Shivani , Freedman Barry I.
Published: September 2019

Background: Given the increasing worldwide prevalence of chronic kidney disease (CKD), it is critical to decrease the associated risk of debilitating vascular complications, including stroke, congestive heart failure, myocardial infarction, and peripheral vascular disease. Treatment options for reducing the risk of all subtypes of stroke in patients with CKD remain limited. For patients with end-stage kidney disease (ESKD), novel applications of noninvasive imaging may help personalize the type of dialysis and dialysis prescription for patients at high-risk. Summary: This manuscript reviews the heightened risk of stroke in patients with nephropathy, including ischemic and hemorrhagic subtypes. Mechanisms associated with increased risk include alterations in cardiac output, platelet function, regional cerebral perfusion, accelerated systemic atherosclerosis, altered blood brain barrier, and disordered neurovascular coupling. There is great potential for noninvasive monitoring of the cerebral vasculature using transcranial Doppler (TCD) to reduce stroke risk, particularly in patients with ESKD. Key Messages: Compared to the general population, patients with CKD are at heightened risk for all subtypes of stroke. This is due to a multitude of mechanisms linking nephropathy with altered cerebral perfusion, cerebral neurovascular coupling, and blood vessel integrity. Intracranial imaging is not currently standard of care practice in patients with CKD or ESKD. TCD may provide clinicians real-time and noninvasive measurement of brain perfusion. This could be useful for assessing risk of stroke in patients’ initiating dialysis, individualizing dialysis prescriptions, and potentially reducing rates of cerebrovascular disease and stroke in high-risk patients.
The Renal Collecting Duct Rises to the Defence
Authors: Xu Qihe
Published: September 2019

When injury occurs, it implies that attack has overcome defence. Tubulointerstitial injury plays important roles in acute kidney injury (AKI) and chronic kidney disease (CKD) and is the common pathway leading to end-stage renal disease, but how the renal tubulointerstitium defends against attack is poorly understood. Emerging evidence suggests that collecting ducts (CDs), which modify urine from nephrons and drain into ureter, could be key defenders protecting tubulointerstitium from injury; furthermore, the canonical renal vitamin A signalling physiologically confined to CDs could be a key regulator of this protective machinery. This hypothesis can be tested by in vitro, in vivo and clinical studies, particularly by repressing or boosting key molecular regulators in CDs, to observe the resulting phenotypes in models of AKI and CKD. Further investigation of this hypothesis could lead to new strategies for diagnosis, prevention and treatment of AKI and CKD.
Bioinformatics Strategies, Challenges, and Opportunities for Next Generation Sequencing-Based HLA Genotyping
Authors: Klasberg Steffen , Surendranath Vineeth , Lange Vinzenz , Schöfl Gerhard
Published: September 2019

The advent of next generation sequencing (NGS) has altered the face of genotyping the human leukocyte antigen (HLA) system in clinical, stem cell donor registry, and research contexts. NGS has led to a dramatically increased sequencing throughput at high accuracy, while being more time and cost efficient than precursor technologies. This has led to a broader and deeper profiling of the key genes in the human immunogenetic make-up. The rapid evolution of sequencing technologies is evidenced by the development of varied short-read sequencing platforms with differing read lengths and sequencing capacities to long-read sequencing platforms capable of profiling full genes without fragmentation. Concomitantly, there has been development of a diverse set of computational analyses and software tools developed to deal with the various strengths and limitations of the sequencing data generated by the different sequencing platforms. This review surveys the different modalities involved in generating NGS HLA profiling sequence data. It systematically describes various computational approaches that have been developed to achieve HLA genotyping to different degrees of resolution. At each stage, this review enumerates the drawbacks and advantages of each of the platforms and analysis approaches, thus providing a comprehensive picture of the current state of HLA genotyping technologies.
Concurrence of Acrodermatitis Enteropathica and Eczema Herpeticum in a Child with Atopic Dermatitis
Authors: Satria Budi , Chen WenChieh , Soebono Hardyanto , Radiono Sunardi , Danarti Retno
Published: September 2019

Acrodermatitis enteropathica (AcE) is a rare, autosomal recessive inherited disorder caused by mutation of the SLC39A4 gene coding for zinc transport protein (ZIP 4). The disease appears during childhood especially in breastfeeding or post-breastfeeding infant. Eczema herpeticum refers to a disseminated skin infection of herpes simplex virus that usually leads to vesicular eruptions commonly seen on a background of atopic dermatitis (AD). We describe an 11-year-old boy with periorificial erosions in periorbital, perinasal, perioral, perineal, and gluteal areas, accompanied with itchy vesicles, some covered with hemorrhagic crusts. A clinical diagnosis of AcE and eczema herpeticum with AD was supported by typical lesions and acute and chronic eczematous changes found mainly in the flexural aspects of extremities, which is diagnostic of AD. Laboratory findings showed anti HSV1 IgG (23.43) and high levels of IgE (478.9 IU/L). There was no multinucleated giant cell in the Tzanck test. Skin histology was compatible with AcE. Direct immunofluorescent examination showed no deposits of IgG, IgM, IgA, or complement. Complete resolution occurred within 2 weeks of acyclovir and oral zinc supplementation.
Call for Action: Benzodiazepine Prescription Prevalence Analysis Shows Off-Label Prescription in One in Eleven Citizens
Authors: López-Pelayo Hugo , Coma Anna , Gual Antoni , Zara Corinne , Lligoña Anna
Published: September 2019

Objective:Benzodiazepines have a good safety profile. Nevertheless, off-label use of these drugs may increase the risk of falls, dependence, and memory loss. Off-label prescription use is not highly prevalent. Studies have not researched the factors that influence off-label prescription use. We aim to identify the prevalence of off-label use of benzodiazepines in Barcelona and explore sociodemographic factors that may be involved for professionals and patients. Method: A cross-sectional study in Barcelona was carried out. Data from professionals were obtained from the Medical Official College of Barcelona. Patients’ healthcare data were extracted from the electronic prescription system DataMart and from the Catalan Health System Observatory (catchment of 97% of the prescription system). Two multivariate analyses were performed to identify risk factors of off-label prescription use; one focused on the patients’ characteristics and the other focused on professionals’ characteristics. Results: In total, 9.7% of Barcelona’s citizens used benzodiazepine prescriptions; 96.1% of them were off-label uses. The most common reason was long-term use (95.8%). Elderly patients were the most common demographic that was exposed to off-label use (OR 1.05, 95% CI 1.04–1.05). Family doctors (B = 38.87, 95% CI 25.25–35.50) and psychiatrists (B = 16.93; 95% CI 11.50–22.35) were the largest groups of off-label prescribers. Conclusions: The prevalence of benzodiazepine off-label prescriptions in our environment is very high, especially when the length of the treatment is considered. Implementation of evidenced-based strategies to facilitate more effective prescription practices is required.
Oncological Outcome and Value of Postoperative Magnetic Resonance Imaging after Focal High-Intensity Focused Ultrasound Therapy for Prostate Cancer
Authors: Rosenhammer Bernd , Niessen Christoph , Rotzinger Laura , Reiss Julian , Schnabel Marco J. , Burger Maximilian , Bründl Johannes
Published: September 2019

Introduction: Focal therapy (FT) by high-intensity focused ultrasound (HIFU) is an emerging option for localized prostate cancer (PC). Due to the lack of long-term data, a close monitoring after FT is essential, but there are still uncertainties about the optimal follow-up regimen. Here we report on a series of FT-HIFU patients with the focus on oncological short-term outcome and the value of postoperative magnetic resonance imaging (MRI). Methods: We included 21 patients treated by FT-HIFU using the Focal One® device (EDAP TMS, France) between November 2015 and May 2018. PC localization was assessed by preoperative multiparametric MRI (mpMRI) and transrectal ultrasound-guided targeted and systematic biopsy. Oncological follow-up included prostate-specific antigen (PSA) development, mpMRI, control biopsies (targeted and systematic) of the treated and untreated areas and salvage treatment rate. Control mpMRI and control biopsy were performed after 6–12 months. Results: 15 patients (71.4%) were managed by focal ablation of a solitary lesion, while 6 patients (28.6%) underwent zonal tumor ablation. All patients underwent control mpMRI and biopsy. After a mean follow-up period of 11.7 months, cancer relapse was detected in 8 patients (38.1%), with 4 patients (19%) having infield recurrence. Postoperative mpMRI revealed 3 out of 4 infield PC relapses but missed 5 out of 7 outfield relapses. Clinically significant cancer recurrence was present in 1 patient (4.8%), which was missed by mpMRI. Posttreatment mpMRI had a sensitivity, specificity, positive and negative predictive value of 62.5, 92.3, 83.3 and 80.0%, respectively, for overall relapse detection based on patient level. Only 1 of the 8 recurrences was suspected based on PSA progression. 4 of the 8 patients with PC relapse (19%) underwent salvage therapy (2 patients by radical prostatectomy, 2 patients by salvage FT-HIFU). Conclusion: Postoperative mpMRI might play a valuable role during follow-up after focal HIFU therapy, particularly in terms of infield relapse detection. Irrespective of mpMRI results, the repeat biopsy regimen should incorporate systematic biopsy including cores of the treated and untreated prostate areas.
A Cribriform Cancer Metastatic to Liver: Case Report and Literature Review
Authors: Gupta Annu , Mallidi Padmaja V. , Grider Douglas J.
Published: September 2019

Metastasis from salivary gland tumors to liver is exceedingly uncommon. Reported is the first case of a mammary analog secretory carcinoma (MASC) of salivary gland origin metastasized to the liver, even after complete surgical resection. A 76 year old female, with past history of a completely extirpated right parotid gland MASC, presented 2 years after right superficial parotidectomy and right neck dissection, with back and flank pain. Subsequent abdominal and pelvic CT revealed multiple small hepatic lesions. Biopsy of the largest hepatic lesion confirmed metastatic MASC of primary parotid gland origin. Both the parotid primary and the hepatic metastases had the confirmatory ETV6 rearrangement by fluorescence in situ hybridization. Although high-grade malignancy and distant metastases of MASC of salivary gland origin to liver is rare, recognizing metastatic MASC potentially alters prognosis and determines therapeutic options.
Correlation between Automated Bone Scan Index Change after Cabazitaxel and Survival among Men with Castration-Resistant Prostate Cancer
Authors: Miyoshi Yasuhide , Sakamoto Shinichi , Kawahara Takashi , Uemura Koichi , Yokomizo Yumiko , Uemura Hiroji
Published: September 2019

Background: Automated bone scan index (aBSI) change (ΔBSI) after treatment and survival in men with prostate cancer remains unclear. We evaluated the correlation between ΔBSI after cabazitaxel and overall survival (OS) in men with bone metastatic castration-resistant prostate cancer (CRPC). Methods: We retrospectively enrolled 32 men with bone metastatic CRPC who had received cabazitaxel. The correlation between ΔBSI from baseline to 16 weeks after starting cabazitaxel and OS was analyzed by multivariate analysis. Results: Median age and time to CRPC were 70.7 years and 9.5 months, respectively. The median cycles of docetaxel before cabazitaxel were eight. Ten (31.2%) patients had visceral metastases at baseline. Median baseline prostate-specific antigen (PSA) was 123.0 ng/mL. The median aBSIs at baseline and 16 weeks after cabazitaxel were 3.2 and 4.4%, respectively. Improvements in aBSI and PSA after 16 weeks of cabazitaxel occurred in 7 (21.9%) and 12 patients (37.5%), respectively. There were no correlations between ΔBSI and OS (p = 0.55), but PSA change was significantly correlated with OS (p = 0.03) by multivariate analysis. Conclusions: This study demonstrated that ΔBSI from baseline to16 weeks after starting cabazitaxel was not correlated with OS among men with bone metastatic CRPC. Further prospective studies may be warranted to confirm the limited utility of aBSI in this setting.
Increased Prevalence of Colorectal Adenomas in Patients with Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study
Authors: Blackett John William , Verna Elizabeth C. , Lebwohl Benjamin
Published: September 2019

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder worldwide. Previous studies have suggested an association between colorectal adenomas and NAFLD but are limited by a lack of biopsy-proven NAFLD or comparison with matched controls. Objectives: We aimed to determine whether histologically demonstrated NAFLD is an independent risk factor for colorectal adenomas. Methods: Patients who underwent liver biopsy showing steatosis who had also undergone screening or surveillance colonoscopy in 2007–2017 were retrospectively studied by manual chart review, excluding patients with liver disease other than NAFLD. Adenoma detection rates and characteristics such as location, histologic type, and size were compared in the resulting 123 NAFLD patients against controls without liver disease matched by age, gender, and endoscopist. Results: Adenoma prevalence was significantly higher in the NAFLD group at 40.7 versus 28.1% in controls (OR 1.87, 95% CI 1.15–3.03, p = 0.01) and remained significant on multivariable analysis controlling for rates of hyperlipidemia, diabetes, and obesity (OR 1.74, 95% CI 1.05–2.88, p = 0.032). Comparing NAFLD patients with advanced fibrosis to those with simple steatosis, there was a trend toward higher adenoma prevalence in advanced fibrosis (50.0 vs. 36.8%; OR 1.84, 95% CI 0.50–6.70, p = 0.36). Conclusions: Patients with histologically demonstrated NAFLD had a significantly higher adenoma prevalence on colonoscopy compared to matched controls, which remained significant after adjusting for rates of diabetes, obesity, and hyperlipidemia. NAFLD should be investigated further as an independent risk factor for colorectal neoplasia.
Diagnostic Potential of Magnetic Resonance Imaging in Chronic Abdominal Pain
Authors: Paajanen Paavo , Lehtimäki Tiina-Talvikki , Fagerström Anne , Paajanen Hannu
Published: September 2019

Introduction: About half of the adult patients suffering from chronic abdominal pain may have no organ-related cause. Our purpose was to evaluate the additional information of magnetic resonance imaging (MRI) in diagnosing the underlying organic causes of such pain. Methods: We performed retrospective audit of 636 consecutive abdominal MRI in patients suffering from nonspecific abdominal pain (NSAP) during years 2014–2017. Medical history, clinical examination, endoscopy reports, and the results of MRI were compared in all patients. The hypothesis was that MRI increases markedly the diagnostic specificity of patients’ symptoms. Results: The mean age of patients was 66 ± 14 years and 60 percent were females. Duration of abdominal pain ranged from 1 month to 30 years (median 1.1 ± 4.0 years). Concurrently with abdominal MRI (n = 636), also ultrasound (n = 106, 17%), colonoscopy (n = 222, 35%), and gastroscopy (n = 217, 34%) were performed. Abdominal MRI revealed additional information in 161/636 (25%) of NSAP patients. Spinal and pelvic bone abnormalities (n = 107) and malignant tumors (n= 31) were the most significant organ-specific findings changing the treatment algorithm. Conclusions: When computerized tomography is not available in outpatient clinics, abdominal MRI increases markedly diagnostic specificity and alters the treatment in 1 of 4 patients suffering from NSAP. Abdominal MRI is therefore suggested for patients suffering from severe symptoms of NSAP.
Risk Factors for Delayed Bleeding after Therapeutic Gastrointestinal Endoscopy in Patients Receiving Oral Anticoagulants: A Multicenter Retrospective Study
Authors: Kubo Kimitoshi , Kato Mototsugu , Mabe Katsuhiro , Harada Naohiko , Iboshi Yoichiro , Kagaya Takashi , Ono Masayoshi , Toyokawa Tatsuya , Yamashita Haruhiro , Kuwai Toshio , Hamada Hiroshige , Sakakibara Yuko , Nishiyama Hitoshi , Ara Nobuyuki , Mori Hideki , Matsumoto Mio , Takahashi Yasuo , Katsushima Shinji , Watanabe Noriko , Ogura Yoshito , Saito Hiroki , Masuda Eiji , Amano Toraji
Published: September 2019

Background/Aims: Delayed bleeding is among the adverse events associated with therapeutic gastrointestinal endoscopy. The aim of this study was to evaluate risk factors for delayed bleeding after gastrointestinal endoscopic resection in patients receiving oral anticoagulants as well as to compare the rates of occurrence of delayed bleeding between the oral anticoagulants used. Methods: We retrospectively analyzed a total of 772 patients receiving anticoagulants. Of these, 389 and 383 patients were receiving direct oral anticoagulants (DOACs) and warfarin, respectively. Therapeutic endoscopic procedures performed included endoscopic submucosal dissection (ESD), endoscopic mucosal resection, polypectomy, and cold polypectomy. Results: Delayed bleeding occurred in 90 patients (11.7%) with no significant difference between the DOAC and warfarin groups (9.5 and 13.8%, respectively). Delayed bleeding occurred significantly more frequently with apixaban than with rivaroxaban (13.5 vs. 6.4%; p < 0.05). A multivariate analysis identified continued anticoagulant therapy (OR 2.29), anticoagulant withdrawal with heparin bridging therapy (HBT; OR 2.18), anticoagulant therapy combined with 1 antiplatelet drug (OR 1.72), and ESD (OR 3.87) as risk factors for delayed bleeding. Conclusion: This study identified continued anticoagulant therapy, anticoagulant withdrawal with HBT, anticoagulant therapy combined with 1 antiplatelet drug, and ESD as risk factors for delayed bleeding after therapeutic endoscopy in patients receiving oral anticoagulants. Delayed bleeding rates were not significantly different between those receiving DOACs and warfarin. It was also suggested that the occurrence of delayed bleeding may vary between different DOACs and that oral anticoagulant withdrawal should be minimized during therapeutic gastrointestinal endoscopy, given the thromboembolic risk involved.
Antidepressant-Like Effect of Bauhinia blakeana Dunn in a Neuroinflammation Model in Mice
Authors: Herrera-Ruiz Maribel , Santillán-Urquiza Mayra A. , Romero-Cerecero Ofelia , Zamilpa Alejandro , Jiménez-Ferrer Enrique , Tortoriello Jaime
Published: September 2019

Objective: To evaluate the antidepressant effect of Bauhinia blakeana and a standardized fraction in the forced swimming test (FST) on mice with neuroinflammation induced with lipopolysaccharides (LPS). Materials and Methods: Evaluation of the antidepressant effect of Bauhinia blakeana hydroalcoholic extract (BbHA) and its fractions was carried out in behavioral tests on mice with LPS-induced neuroinflammation. Results: BbHA had a significant antidepressant effect, measured on healthy mice in the FST. Bio-guided chemical separation of the extract produced a methanolic fraction (BbMe), which decreased the immobility time in FST. In this test, the intraperitoneal administration of LPS induced depression in mice, and BbHA and BbMe counteracted this effect, significantly decreasing the induced depression. Quantification of inflammatory mediators (IL-10, IL-4, IL-6, IL-1β, and TNF-α) in the brain demonstrated that BbHA and BbMe effectively decreased the effect of LPS on the brain concentration of all measured cytokines. Conclusions: Bauhinia blakeana produced an antidepressant effect, while BbMe also exerted a modulating effect, on the damage induced by LPS. Rutin, a glycosylated flavonoid, was identified as the main compound in the active fraction, which could mediate in the antidepressant and immunomodulatory effect.