Jonas W Bartstra, Fieke Draaisma, Sabine R Zwakenberg, Nikolas Lessmann, Jelmer M Wolterink, Yvonne T van der Schouw, Pim A de Jong, Joline W J Beulens
PURPOSE: Vitamin K-dependent proteins are involved in (patho)physiological calcification of the vasculature and the bones. Type 2 diabetes mellitus (DM2) is associated with increased arterial calcification and increased fractures. This study investigates the effect of 6 months vitamin K2 supplementation on systemic arterial calcification and bone mineral density (BMD) in DM2 patients with a history of cardiovascular disease (CVD). METHODS: In this pre-specified, post hoc analysis of a double-blind, randomized, controlled clinical trial, patients with DM2 and CVD were randomized to a daily, oral dose of 360 µg vitamin K2 or placebo for 6 months...
October 17, 2020: European Journal of Nutrition
R Brockman, A Wills, T M Greiling, S Leitenberger, N Fett
Calcinosis cutis, although common in systemic sclerosis, has been rarely reported in patients with morphea. We describe four patients with calcinosis cutis arising within morphea plaques, discuss their treatments and outcomes, and review previously published cases. Current management recommendations for concomitant morphea and dystrophic calcinosis cutis are based on limited data and expert opinion, which has primarily focused on reduction of active inflammation and reduction of symptoms related to calcinosis or ulceration...
June 15, 2020: Dermatology Online Journal
Louise Oni, Rachael D Wright, Stephen Marks, Michael W Beresford, Kjell Tullus
Systemic lupus erythematosus is a rare lifelong multi-systemic autoimmune condition. Juvenile-onset SLE (JSLE) is recognized to have a more active disease course when compared with adult-onset disease and patients have a worse long-term survival. Kidney involvement occurs in over 50% of children and treatment decisions are guided by the histological classification. Several international groups have produced treatment protocols that rely on an intense period of immunosuppression to halt the acute kidney inflammatory process, followed by maintenance therapy with close observation for disease improvement and prompt evaluation of disease flares...
July 28, 2020: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Maurits F J M Vissers, Adam F Cohen, Joop M A van Gerven, Geert Jan Groeneveld
During the outbreak of the COVID-19 pandemic many clinical trials were abruptly halted. Measures to contain the pandemic are currently taking effect and societies in general and health care systems in particular are considering how to return to normalcy. This opens-up the discussion when and how clinical trials should be restarted while the COVID-19 pandemic has not yet resolved, and what should happen in case of a resurgence of the virus in the coming months. This article uses the Four Ethical Principles framework as a structured approach to come to a set of practical, ethically grounded guidelines for halting and relaunching clinical trials during the SARS-CoV-2 pandemic...
July 15, 2020: British Journal of Clinical Pharmacology
Shota Kuwabara, Joe Matsumoto, Hiroyasu Tojima, Hideyuki Wada, Kohei Kato, Yukiko Tabata, Masaomi Ichinokawa, Tatsuya Yoshioka, Katsuhiko Murakawa, Atsushi Ikeda, Setsuyuki Ohtake, Koichi Ono
BACKGROUND: Pancreatoduodenectomy with resection of the portal vein or superior mesenteric vein confluence has been safely performed in patients with pancreatic head cancer associated with infiltration of the portal vein or superior mesenteric vein. In recent years, left-sided portal hypertension, a late postoperative complication, has received focus owing to increased long-term survival with advances in chemotherapy. Left-sided hypertension may sometimes cause fatal gastrointestinal bleeding because of the rupture of gastrointestinal varices...
June 3, 2020: Surgical Case Reports
William A Marston, Robert S Kirsner, Arthur Tallis, Jason R Hanft, Jodi Walters, Alik Farber
BACKGROUND: Limb compression is a key component of protocols used to heal venous leg ulcers (VLUs). A novel ambulatory pneumatic compression device was tested in comparison with multilayered bandage (MLB) compression systems for the treatment of VLUs in a prospective randomized clinical trial. METHODS: Patients with VLUs measuring 1.5 to 50 cm2 with duration of 1 to 24 months were randomized to treatment with a pneumatic compression device, the ACTitouch adaptive compression therapy (ACT) system (Tactile Medical, Minneapolis, Minn), or MLB...
May 22, 2020: Journal of Vascular Surgery. Venous and Lymphatic Disorders
Miglë Žiemytė, Juan C Rodríguez-Díaz, María P Ventero, Alex Mira, María D Ferrer
Microorganisms grown in biofilms are more resistant to antimicrobial treatment and immune system attacks compared to their planktonic forms. In fact, infections caused by biofilm-forming Staphylococcus aureus and Staphylococcus epidermidis are a large threat for public health, including patients with medical devices. The aim of the current manuscript was to test the effect of dalbavancin, a recently developed lipoglycopeptide antibiotic, alone or in combination with compounds contributing to bacterial cell disaggregation, on staphylococcal biofilm formation and elimination...
2020: Frontiers in Microbiology
Marcus Deloney, Kyra Smart, Blaine A Christiansen, Alyssa Panitch
Inflammation following joint trauma contributes to cartilage degradation and progression of post traumatic osteoarthritis (PTOA). Therefore, drug delivery vehicles that deliver effective anti-inflammatory treatments have the potential to prevent PTOA. We have developed solid and hollow, thermoresponsive nanoparticles for the controlled release of our anti-inflammatory MK2-inhibiting (MK2i) peptide for intra-articular injection to halt inflammation that contributes to the advancement of PTOA. This system exploits the thermosensitive characteristic of N-isopropyl acrylamide (NIPAm) to transition phases when passing through its lower critical solution temperature (LCST)...
April 9, 2020: Journal of Controlled Release
Xin Li, Jane Kim, Jiabin Wu, Alaa' I Ahamed, Yinsheng Wang, Manuela Martins-Green
Chronic wounds are a major global health problem with the presence of biofilm significantly contributing to wound chronicity. Current treatments are ineffective in resolving biofilm and simultaneously killing the bacteria; therefore, effective biofilm-resolving drugs are needed. We have previously shown that, together with α -tocopherol, N -acetyl-cysteine (NAC) significantly improves the healing of biofilm-containing chronic wounds, in a diabetic mouse model we developed, by causing disappearance of the bacteria and breakdown of the extracellular polymeric substance (EPS)...
2020: Journal of Diabetes Research
Saffire H Krance, Russell Luke, Marc Shenouda, Ahmad R Israwi, Sarah J Colpitts, Lina Darwish, Maximilian Strauss, Joel C Watts
Prions, which cause fatal neurodegenerative disorders such as Creutzfeldt-Jakob disease (CJD), are misfolded and infectious protein aggregates. Currently, there are no treatments available to halt or even delay the progression of prion disease in the brain. The infectious nature of prions has resulted in animal paradigms that accurately recapitulate all aspects of prion disease, and these have proven to be instrumental for testing the efficacy of candidate therapeutics. Nonetheless, infection of cultured cells with prions provides a much more powerful system for identifying molecules capable of interfering with prion propagation...
January 14, 2020: Journal of Neurochemistry
William Shield, Ashley Cellini, Hongying Tian, Kim Wilson, Yang Dan, Joshua M Abzug, Sonia Garcia, Norifumi Moritani, Ivan Alferiev, Michael Chorny, Masaharu Takigawa, Vincent Y Ng, Masahiro Iwamoto, Motomi Enomoto-Iwamoto
Chondrosarcoma is the second most common primary bone sarcoma. Treatment of chondrosarcoma is limited to surgery due to radiation and chemotherapy resistance of this cancer. An ideal treatment for chondrosarcoma would be a well-tolerated, minimally invasive local or systemic treatment modality to halt or slow tumor growth prior to resection of local, unresectable local, or metastatic disease. Palovarotene, an agonist of nuclear retinoic acid receptor gamma (RARγ) has shown therapeutic actions for heterotopic ossification and osteochondroma without serious adverse effects in animal models...
December 6, 2019: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
Long V Nguyen, Karlee Searle, Katarzyna J Jerzak
Importance: Metastatic breast cancer with central nervous system (CNS) metastases carries a poor prognosis. Recently, CDK4/6 inhibitors have demonstrated a progression free survival (PFS) and overall survival benefit when combined with standard endocrine therapy in advanced hormone receptor (HR)+/HER2- breast cancer. Pre-clinical data suggests possible activity of CDK4/6 inhibitors in the brain, but their CNS-specific benefit has not been explored in clinical practice. Methods: We reviewed clinical trials investigating the efficacy of CDK4/6 inhibitors for advanced or metastatic HR+/HER2- breast cancer...
October 29, 2019: Oncotarget
Kelly N Hassell
Histone deacetylases (HDAC) and histone deacetylase inhibitors (HDACi) have greatly impacted the war on cancer. Their role in epigenetics has significantly altered the development of anticancer drugs used to treat the most rare, persistent forms of cancer. During transcription, HDAC and HDACi are used to regulate the genetic mutations found in cancerous cells by removing and/or preventing the removal of the acetyl group on specific histones. This activity determines the relaxed or condensed conformation of the nucleosome, changing the accessibility zones for transcription factors...
November 1, 2019: Diseases (Basel)
R Balestrino, A H V Schapira
Parkinson disease (PD) is the most common neurodegenerative movement disorder. In Europe, prevalence and incidence rates for PD are estimated at approximately 108-257/100 000 and 11-19/100 000 per year, respectively. Risk factors include age, male gender and some environmental factors. The aetiology of the disease in most patients is unknown, but different genetic causes have been identified. Although familial forms of PD account for only 5%-15% of cases, studies on these families provided interesting insight on the genetics and the pathogenesis of the disease allowing the identification of genes implicated in its pathogenesis and offering critical insights into the mechanisms of disease...
January 2020: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
Ram Haddas, Kevin L Ju, Akwasi Boah, Thomas Kosztowski, Peter B Derman
STUDY DESIGN: A prospective cohort study. OBJECTIVE: Quantify the extent of change in dynamic balance and stability in a group of patients with cervical spondylotic myelopathy (CSM) after cervical decompression surgery and to compare them with matched healthy controls. SUMMARY OF BACKGROUND DATA: CSM is a naturally progressive degenerative condition that commonly results in loss of fine motor control in the hands and upper extremities and in gait imbalance...
November 2019: Clinical Spine Surgery
Ghassan K Abou-Alfa, Qian Shi, Jennifer J Knox, Andreas Kaubisch, Donna Niedzwiecki, James Posey, Benjamin R Tan, Petr Kavan, Rakesh Goel, Philip E Lammers, Tanios S Bekaii-Saab, Vincent C Tam, Lakshmi Rajdev, Robin K Kelley, Imane El Dika, Tyler Zemla, Ryan I Potaracke, Jennifer Balletti, Anthony B El-Khoueiry, James H Harding, Jennifer M Suga, Lawrence H Schwartz, Richard M Goldberg, Monica M Bertagnolli, Jeffrey Meyerhardt, Eileen M O'Reilly, Alan P Venook
Importance: Previous communication has reported significant improvement in overall survival (OS) when using doxorubicin plus sorafenib in the treatment of advanced hepatocellular cancer (HCC). Objective: To determine if doxorubicin added to sorafenib therapy improves OS, with stratification for locally advanced and metastatic disease. Design, Setting, and Participants: This unblinded randomized phase 3 clinical trial was led by Alliance in collaboration with Eastern Cooperative Oncology Group-American College of Radiology Imaging Network, Canadian Cancer Trials Group, and Southwest Oncology Group...
September 5, 2019: JAMA Oncology
Beatriz Mothe, Christian Manzardo, Alvaro Sanchez-Bernabeu, Pep Coll, Sara Morón-López, Maria C Puertas, Miriam Rosas-Umbert, Patricia Cobarsi, Roser Escrig, Núria Perez-Alvarez, Irene Ruiz, Cristina Rovira, Michael Meulbroek, Alison Crook, Nicola Borthwick, Edmund G Wee, Hongbing Yang, Jose M Miró, Lucy Dorrell, Bonaventura Clotet, Javier Martinez-Picado, Christian Brander, Tomáš Hanke
Background: Strong and broad antiviral T-cell responses targeting vulnerable sites of HIV-1 will likely be a critical component for any effective cure strategy. Methods: BCN01 trial was a phase I, open-label, non-randomized, multicenter study in HIV-1-positive individuals diagnosed and treated during early HIV-1 infection to evaluate two vaccination regimen arms, which differed in the time (8 versus 24 week) between the ChAdV63.HIVconsv prime and MVA.HIVconsv boost vaccinations...
May 2019: EClinicalMedicine
Berkley E Gryder, Lei Wu, Girma M Woldemichael, Silvia Pomella, Taylor R Quinn, Paul M C Park, Abigail Cleveland, Benjamin Z Stanton, Young Song, Rossella Rota, Olaf Wiest, Marielle E Yohe, Jack F Shern, Jun Qi, Javed Khan
Identity determining transcription factors (TFs), or core regulatory (CR) TFs, are governed by cell-type specific super enhancers (SEs). Drugs to selectively inhibit CR circuitry are of high interest for cancer treatment. In alveolar rhabdomyosarcoma, PAX3-FOXO1 activates SEs to induce the expression of other CR TFs, providing a model system for studying cancer cell addiction to CR transcription. Using chemical genetics, the systematic screening of chemical matter for a biological outcome, here we report on a screen for epigenetic chemical probes able to distinguish between SE-driven transcription and constitutive transcription...
July 8, 2019: Nature Communications
Jakub P Hlavka, Soeren Mattke, Jodi L Liu
No disease-modifying therapy is currently available for Alzheimer's disease, but therapies are in development, and one may become available in the near future. Based on results from early-stage clinical trials, therapeutic development has focused on the hypothesis that Alzheimer's dementia must be prevented rather than cured, because candidate treatments have not been able to reverse the course of dementia. Thus, current trials target patients with early-stage Alzheimer's disease. Were a therapy to become available, patients could undergo first screening for signs of early-stage memory loss or mild cognitive impairment (MCI), testing for the Alzheimer's disease pathology, and then treatment with the aim of halting or slowing progression to Alzheimer's dementia...
May 2019: Rand Health Quarterly
Meagan A Barry, Leroy Versteeg, Qian Wang, Jeroen Pollet, Bin Zhan, Fabian Gusovsky, Maria Elena Bottazzi, Peter J Hotez, Kathryn M Jones
Chagas disease, caused by the parasite Trypanosoma cruzi, develops into chronic Chagas' cardiomyopathy in ~30% of infected individuals, characterized by conduction disorders, arrhythmias, heart failure, and even sudden cardiac death. Current anti-parasitic treatments are plagued by significant side effects and poor efficacy in the chronic phase of disease; thus, there is a pressing need for new treatment options. A therapeutic vaccine could bolster the protective TH1-mediated immune response, thereby slowing or halting the progression of chronic Chagas' cardiomyopathy...
May 2019: PLoS Neglected Tropical Diseases
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