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Pranav R H Joshi, Laura Cervera, Ibrahim Ahmed, Oleksandr Kondratov, Sergei Zolotukhin, Joseph Schrag, Parminder S Chahal, Amine A Kamen
Despite numerous advancements in production protocols, manufacturing AAV to meet exceptionally high demand (1016 -1017 viral genomes [VGs]) in late clinical stages and for eventual systemic delivery poses significant challenges. Here, we report an efficient, simple, scalable, robust AAV5 production process utilizing the most recent modification of the OneBac platform. An increase in volumetric yield of genomic particles by ∼6-fold and functional particles by ∼20-fold was achieved by operating a high-cell-density process in shake flasks and bioreactors that involves an Sf9-based rep/cap stable cell line grown at a density of about 10 million cells/mL infected with a single baculovirus...
June 14, 2019: Molecular Therapy. Methods & Clinical Development
Yoshitsugu Nakamura, Miho Kuroda, Yujiro Ito, Takahiko Masuda, Shuhei Nishijima, Takahisa Hirano, Shinichi Hisasue
OBJECTIVE: The da Vinci Xi surgical system (Intuitive Surgical, Sunnyvale, CA, USA) cannot give tactile feedback to surgeons. This shortcoming may increase the risk of left internal thoracic artery (LITA) injury during its harvest. We utilized Firefly Fluorescence Imaging (Firefly) to assess LITA quality in robot-assisted minimally invasive direct coronary artery bypass (R-MIDCAB). METHODS: We retrospectively reviewed clinical records and intraoperative videos of 30 consecutive patients who underwent R-MIDCAB with LITA-left anterior descending (LAD) coronary bypass...
March 18, 2019: Innovations: Technology and Techniques in Cardiothoracic and Vascular Surgery
Cristiano Silva Cruz, Valentina Tosatto, Paula Oliveira Nascimento, Rita Barata Moura
Hepatic hydrothorax, a rare and debilitating complication of cirrhosis, carries high morbidity and mortality. First-line treatment consists of dietary sodium restriction and diuretic therapy. Some patients, mainly those who are refractory to medical management, will require invasive pleural drainage. The authors report the case of a 76-year-old man in a late cirrhotic stage of alcoholic chronic liver disease, presenting with recurrent right-sided hepatic hydrothorax, portal hypertension, hepatosplenomegaly and thrombocytopaenia...
March 15, 2019: BMJ Case Reports
Antonio Serrano-Albarrás, Sergi Cirera-Rocosa, Daniel Sastre, Irene Estadella, Antonio Felipe
Rheumatoid arthritis (RA) is a serious autoimmune disease that has severe impacts on both the wellbeing of patients and the economy of the health system. Similar to many autoimmune diseases, RA concurs with a long evolution, which eventually results in highly debilitating symptoms. Therapeutic treatments last for long periods during RA. However, their efficiency and side effects result in suboptimal conditions. Therefore, the need for specific, safer and nontoxic alternatives for the treatment of RA is essential...
March 13, 2019: Biochemical Pharmacology
Fumihiro Terasaki, Yusuke Yamamoto, Katsuhisa Ohgi, Teiichi Sugiura, Yukiyasu Okamura, Takaaki Ito, Ryo Ashida, Katsuhiko Uesaka
BACKGROUND: A right-sided ligamentum teres (RSLT) is a rare congenital anomaly in which the fetal umbilical vein is connected to the right paramedian trunk. RSLT creates difficulty in liver resection with respect to decision-making regarding the resection line, deviation of the vasculobiliary architecture. We report a case in which laparoscopic left lateral sectionectomy (LLLS) was performed to treat colorectal liver metastasis (CRLM) in a patient with RSLT. CASE PRESENTATION: A 63-year-old man with a past history of rectal cancer presented to our institution due to liver metastasis in the left lateral section from rectal cancer...
March 15, 2019: Surgical Case Reports
Jun Watanabe, Atsushi Ishibe, Yusuke Suwa, Hirokazu Suwa, Mitsuyoshi Ota, Chikara Kunisaki, Itaru Endo
BACKGROUND: Recent studies have shown the potential benefit of indocyanine green fluorescence imaging (ICG-FI) in lowering the anastomotic leakage (AL) rates by changing the surgical plan. The aim of this study was to evaluate the effect of ICG-FI on the AL rates in laparoscopic low anterior resection (LAR) for rectal cancer. METHODS: From September 2014 to December 2017, data from patients who underwent laparoscopic LAR for rectal cancer were collected and analyzed...
March 14, 2019: Surgical Endoscopy
Xiaofeng Chen, Tianzhu Qiu, Yingwei Zhu, Jing Sun, Ping Li, Biao Wang, Peinan Lin, Xiaomin Cai, Xiao Han, Fengjiao Zhao, Yongqian Shu, Lianpeng Chang, Hua Jiang, Yanhong Gu
LESSONS LEARNED: Patients with metastatic colorectal cancer with good performance status or no liver metastasis could benefit from apatinib.Circulating tumor DNA abundance may be a predictor in serial monitoring of tumor load. BACKGROUND: Apatinib, an oral vascular endothelial growth factor (VEGF) receptor-2 inhibitor, has been approved as third-line treatment for metastatic gastric cancer in China. The aim of this study was to evaluate the efficacy and safety of apatinib, in the treatment of patients with refractory metastatic colorectal cancer after failure of two or more lines of chemotherapy...
March 15, 2019: Oncologist
Lalathaksha Kumbar, Jerry Yee
Infection-related causes are second only to cardiovascular events for mortality among end-stage renal disease patients. This review will provide an overview of hemodialysis catheter-, graft-, and fistula-related infections with emphasis on diagnosis and management in specific settings. Use of catheters at the initiation of dialysis has remained unchanged at 80%. Of all access-related bloodstream infections (BSIs), 70% occur in patients with catheters. The risk factors for BSIs in tunneled, cuffed catheters include the duration of the catheter, past catheter-related bacteremia, left-sided internal jugular vein catheters, hypoalbuminemia, and immunosuppression...
January 2019: Advances in Chronic Kidney Disease
Thuy Le, Abhijit Kundu, Atanu Goshal, Nghi Nguyen, Sarah Preston, Yaqing Jiao, Banfeng Ruan, Lian Xue, Fei Huang, Jennifer Keiser, Andreas Hofmann, Bill Chang, Jose Garcia-Bustos, Timothy N C Wells, Michael J Palmer, Abdul Jabbar, Robin B Gasser, Jonathan B Baell
A phenotypic screen of two different libraries of small molecules for inhibition of the development of larvae of the parasitic nematode Haemonchus contortus led to the identification of two 1-methyl-1H-pyrazole-5-carboxamide derivatives, namely tolfenpyrad and the other designated SN00799639, with IC50 values of 0.03 and 0.29 µM, respectively. Their structural similarities and differences lent themselves to construction of molecular hybrids. Medicinal chemistry optimization targeted modifications of the left-hand side (LHS), middle section and right-hand side (RHS) of the hybrid structure of these two hits, in order to elucidate the structure-activity relationship (SAR)...
March 15, 2019: Journal of Medicinal Chemistry
Antongiulio Faggiano, Silvana Di Maio, Carmela Mocerino, Margaret Ottaviano, Chiara De Divitiis, Valentina Guarnotta, Pasquale Dolce, Roberta Modica, Ivana Puliafito, Lucia Tozzi, Antonella Di Sarno, Silvana Leo, Ferdinando Riccardi, Giovannella Palmieri, Salvatore Tafuto, Antonella Bianco, Giuseppe Badalamenti, Annamaria Colao
PURPOSE: Many different treatments are suggested by guidelines to treat grade 1-2 (G1-G2) neuroendocrine tumors (NET). However, a precise therapeutic algorithm has not yet been established. This study aims at identifying and comparing the main therapeutic sequences in G1-G2 NET. METHODS: A retrospective observational Italian multicenter study was designed to collect data on therapeutic sequences in NET. Median progression-free survival (PFS) was compared between therapeutic sequences, as well as the number and grade of side effects and the rate of dose reduction/treatment discontinuation...
March 14, 2019: Endocrine
Jelena Popović, Andrijana Klajn, Tatjana Paunesku, Qing Ma, Si Chen, Barry Lai, Milena Stevanović, Gayle E Woloschak
Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect of platinum-based chemotherapy and decreases the quality of life of cancer patients. We compared neuroprotective properties of several agents using an in vitro model of terminally differentiated human cells NT2-N derived from cell line NT2/D1. Sodium azide and an active metabolite of amifostine (WR1065) increase cell viability in simultaneous treatment with cisplatin. In addition, WR1065 protects the non-dividing neurons by decreasing cisplatin caused oxidative stress and apoptosis...
March 14, 2019: Cellular and Molecular Neurobiology
F Gohlke, B Werner, I Wiese
OBJECTIVE: The aim of the surgical technique is the stable fixation of a glenoid baseplate and reconstruction of bone loss with correction of version, inclination, and medialization of the joint line. INDICATIONS: Significant glenoid bone loss due to glenoid loosening or wear in revision shoulder arthroplasty. CONTRAINDICATIONS: Active infection, inoperability due to poor health condition. SURGICAL TECHNIQUE: Reconstruction of advanced glenoid bone stock in case of glenoid loosening of total shoulder arthroplasty can be performed either with autografts and allografts or metallic augmentation together with reverse baseplates in a one- or two-stage procedure...
March 15, 2019: Operative Orthopädie und Traumatologie
Qi Zhang, Sang Beom Lee, Xu Chen, Morgan Stevenson, Jing Pan, Donghai Xiong, Yu Zhou, Mark Miller, Ronald A Lubet, Yian Wang, Shama Mirza, Ming You
Bexarotene has exhibited inhibitory effects in preclinical models of lung, mammary gland tumorigenesis and in phase I/II trials of non-small cell lung cancer. The major side effects of bexarotene when administered orally were hypertriglyceridemia and hypercholesterolemia. In our previous study we demonstrated that aerosolized bexarotene through nasal inhalation exhibited potent chemopreventive activity in a lung adenoma preclinical model without the hypertriglyceridemia. To facilitate its future clinical translation, we modified the formula of the aerosolized bexarotene with a clinically relevant solvent system...
March 15, 2019: Nano Letters
D Kachlik, T Vobornik, V Dzupa, Z Marvanova, O Toupal, E Navara, N Stevulova, V Baca
INTRODUCTION: Blood vessels passing through pelvic region come into intimate contact with pelvic bone and can be injured by the sharp edges of the dislocated fracture fragments. The aim of the study was to evaluate the influence of localization, shape and dislocation of individual pelvic ring bones' fractures on arterial injuries. MATERIALS AND METHODS: The study group consisted of 474 patients enrolled in a one-year prospective multicenter study. The pattern of pelvic fracture lines were characterized and recorded on a planar diagram of the subjected side of the pelvis...
March 14, 2019: Clinical Anatomy
Tan Li, Zhu Baochen, Zhang Yue, Wang Cheng, Wu Yali, Sun Zongxi, Zhang Wantong, Lu Yang, Du Shouying
Docetaxel is the widely-used first-line therapy to treat lung cancer around the world. However, tumor progression and severe side effect occurred in some patients with docetaxel treatment. Most of the side effects were caused by immunocompromise, which limits the long-term use of docetaxel. Shenqi Fuzheng (SQFZ) injection has been used as adjuvant therapy to treat lung cancer which may enhance immunity as well. Owing to the complexity of drug combination, the mechanism of SQFZ injection in combination with docetaxel on lung cancer remains unclear...
March 14, 2019: Scientific Reports
David Roofeh, Sara Jaafar, Dharshan Vummidi, Dinesh Khanna
PURPOSE OF REVIEW: To review the recently published data and provide a practical overview for management of systemic sclerosis-interstitial lung disease (SSc-ILD). RECENT FINDINGS: Published evidence shows considerable practitioner variability in screening patients for ILD. Recent published data support use of cyclophosphamide or mycophenolate mofetil as first-line treatment of SSc-ILD. For patients not responding to first-line therapies, consideration is given to rituximab as rescue therapy...
March 5, 2019: Current Opinion in Rheumatology
Anna-Maija Talvitie, Hanna Ojala, Teuvo Tammela, Anna-Maija Koivisto, Ilkka Pietilä
BACKGROUND: Localised prostate cancer affects patient's quality of life in many ways. The aim of this study was to explore factors related to self-rated health and life satisfaction for patients treated for prostate cancer, and to compare the results of these generic quality-of-life measures to the prostate cancer-specific quality-of-life measure (UCLA Prostate Cancer Index), which focuses on physical functioning. MATERIAL AND METHODS: This cross-sectional survey was carried out among 183 men who underwent radical prostatectomy in 2012-2015 at a university hospital in Finland and were seen 1 year postsurgery...
March 13, 2019: Scandinavian Journal of Caring Sciences
Yuxi Chen, Hongjun Chen, Hui Xie, Shaohui Yuan, Chuanbo Gao, Lei Yu, Zhenggang Bi
Osteosarcoma (OS) is the predominant form of primary bone malignancy in children and adolescents. Although the combination of chemotherapy and modified surgical therapy leads to marked improvements in the survival rate, the therapeutic outcomes remain unsatisfactory. Therefore, the identification of novel drugs with higher efficacy and fewer side‑effects is urgently required. Proteasome inhibitors have been approved by the Food and Drug Administration (FDA) for the treatment of certain cancers, although none of them are directed against OS...
March 1, 2019: Oncology Reports
Yusuke Kawai, Masataka Banshodani, Misaki Moriishi, Tomoyasu Sato, Sadanori Shintaku, Takao Masaki, Hideki Kawanishi
Iliopsoas abscess in hemodialysis patients is rare. We examined nine hemodialysis patients with iliopsoas abscess (six men, five diabetes mellitus cases) treated between 2005 and 2015. Mean age and dialysis vintage at onset were 72 years and 109 months, respectively. Of the nine patients, four had lumbar orthopedic diseases, and two had all components of the classic triad of iliopsoas abscess at onset. All nine patients underwent percutaneous drainage, while seven underwent antimicrobial therapy. The most common pathogenic bacterium was methicillin-resistant Staphylococcus aureus (MRSA) (n = 5)...
March 12, 2019: Therapeutic Apheresis and Dialysis
Y C Hao, C L Xiao, J Lu, K Liu, Y Q Liu, L L Ma
Objective: To investigate application value of "point-line-surface-volume" four dimensional holmium laser enucleation of prostate (HoLEP) in the treatment of benign prostatic hyperplasia (BPH). Methods: From December 2016 to November 2017, the clinical data of 60 cases of BPH with the treatment of "Point-line-surface-volume" four dimensional HoLEP at Department of Urology, Peking University Third Hospital were analyzed retrospectively. The age was (73.8±8.0) years (range: 60 to 96 years), body mass index was (23...
March 1, 2019: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
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