Medicine and Health Sciences Commons^™

A New Hcc Model Induced By Co-Overexpression Fgf19 And Met In Mice, Junyan Tao 8598903, Morgan Preziosi, Sucha Singh, Xin Chen, Satdarshan (Paul) Singh Monga

Hepatobiliary Cancers: Pathobiology and Translational Advances

No abstract provided.

Convergence Of Wnt/Beta-Catenin And Mtor Signaling In Liver Physiology And Hepatocellular Carcinoma, Adeola O. Adebayo Michael, Junyan Tao, Satdarshan P. Monga

Hepatobiliary Cancers: Pathobiology and Translational Advances

No abstract provided.

Bile Acids Contribute To The Gender-Biased Incidence Of Hcc, Megan E. Patton, Sherwin H. Kelekar, Rhishikesh Thakare, Yazen Alnouti, Sayeepriyadarshini Anakk

Hepatobiliary Cancers: Pathobiology and Translational Advances

No abstract provided.

Autophagy Is Involved In Hdac6 Mediated Ciliary Loss, And Increases Malignancy In Cholangiocarcinoma Models, Estanislao Peixoto, Stephanie Holtorf, Kristen Thelen M. Thelen, Maria J. Lorenzo Pisarello, Nicholas F. Larusso, Sujeong Jin, Sergio A. Gradilone

Hepatobiliary Cancers: Pathobiology and Translational Advances

No abstract provided.

Identification Of Common Molecular Subtypes Of Asian Hepatocellular Carcinoma And Cholangiocarcinoma., Anuradha Budhu, Jittiporn Chaisaingmongkol, Hien Dang, So Mee Kwon, Siritida Rabibhadana, Benjarath Pupacdi, Marshonna Forgues, Yosawat Pomyen, Vajarabhongsa Bhudhisawasdi, Nirush Lertprasertsuke, Anon Chotirosniramit, Chawalit Pairojkul, Chirayu Auewarakul, Thaniya Sricharunrat, Kannika Phornphutku, Suleeporn Sangrajrang, Maggie Cam, Ping He, Stephen M. Hewitt, Xiaolin Wu, Snorri S. Thorgeirsson, Paul S. Meltzer, Christopher Loffredo, Robert H. Wiltrout, Curtis C. Harris, Chulabhorn Mahidol, Mathuros Ruchirawat, Xin W. Wang

Hepatobiliary Cancers: Pathobiology and Translational Advances

No abstract provided.

Clarithromycin Attenuates Il-13–Induced Periostin Production In Human Lung Fibroblasts, Kosaku Komiya, Shoichiro Ohta, Kazuhiko Arima, Masahiro Ogawa, Shoichi Suzuki, Yasutaka Mitamura, Satoshi Nunomura, Yasuhiro Nanri, Tomohito Yoshihara, Atsushi Kawaguchi, Jun-Ichi Kadota, Bruce K. Rubin, Kenji Izuhara

Biochemistry and Molecular Biology Publications

Background

Periostin is a biomarker indicating the presence of type 2 inflammation and submucosal fibrosis; serum periostin levels have been associated with asthma severity. Macrolides have immunomodulatory effects and are considered a potential therapy for patients with severe asthma. Therefore, we investigated whether macrolides can also modulate pulmonary periostin production.

Methods

Using quantitative PCR and ELISA, we measured periostin production in human lung fibroblasts stimulated by interleukin-13 (IL-13) in the presence of two 14-member–ring macrolides—clarithromycin or erythromycin—or a 16-member–ring macrolide, josamycin. Phosphorylation of signal transducers and activators of transcription 6 (STAT6), downstream of IL-13 signaling, was evaluated by Western blotting. …

Neutralization Of Diverse Human Cytomegalovirus Strains Conferred By Antibodies Targeting Viral Gh/Gl/Pul128-131 Pentameric Complex, Sha Ha, Fengsheng Li, Matthew C. Troutman, Daniel C. Freed, Aimin Tang, John W. Loughney, Dai Wang, I-Ming Wang, Josef Vlasak, David C. Nickle, Richard R. Rustandi, Melissa Hamm, Pete A. Dephillips, Ningyan Zhang, Jason S. Mclellan, Hua Zhu, Stuart P. Adler, Michael A. Mcvoy, Zhiqiang An, Tong-Ming Fu

Biochemistry and Molecular Biology Publications

Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection, and developing a prophylactic vaccine is of high priority to public health. We recently reported a replication-defective human cytomegalovirus with restored pentameric complex glycoprotein H (gH)/gL/pUL128-131 for prevention of congenital HCMV infection. While the quantity of vaccine-induced antibody responses can be measured in a viral neutralization assay, assessing the quality of such responses, including the ability of vaccine-induced antibodies to cross-neutralize the field strains of HCMV, remains a challenge. In this study, with a panel of neutralizing antibodies from three healthy human donors with natural HCMV infection or a …

Uncovering Precision Phenotype-Biomarker Associations In Traumatic Brain Injury Using Topological Data Analysis, Jessica L. Nielson, Shelly R. Cooper, John K. Yue, Marco D. Sorani, Tomoo Inoue, Esther L. Yuh, Pratik Mukherjee, Tanya C. Petrossian, Jesse Paquette, Pek Y. Lum, Gunnar E. Carlsson, Mary J. Vassar, Hester F. Lingsma, Wayne A. Gordon, Alex B. Valadka, David O. Okonkwo, Geoffrey T. Manley, Adam R. Ferguson, Track-Tbi Investigators

Neurosurgery Publications

Background

Traumatic brain injury (TBI) is a complex disorder that is traditionally stratified based on clinical signs and symptoms. Recent imaging and molecular biomarker innovations provide unprecedented opportunities for improved TBI precision medicine, incorporating patho-anatomical and molecular mechanisms. Complete integration of these diverse data for TBI diagnosis and patient stratification remains an unmet challenge.

Methods and findings

The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Pilot multicenter study enrolled 586 acute TBI patients and collected diverse common data elements (TBI-CDEs) across the study population, including imaging, genetics, and clinical outcomes. We then applied topology-based data-driven discovery to …

Natural History Of Acute Subdural Hematoma, Rafael A. Vega, Alex B. Valadka

Neurosurgery Publications

• Although guidelines for surgical decision-making in patients with acute subdural hematomas (ASDHs) are widely available, the evidence supporting these guidelines is weak, and management of these patients must often be individualized.
• Smaller ASDHs in patients in good neurologic condition usually can be successfully managed without surgery.
• Large ASDHs with minimal mass effect in patients with minimal symptoms also may be considered for nonoperative management.
• The literature is divided about the effects of anticoagulant and antiplatelet medications on rapid growth of ASDHs and on their likelihood of progression to large chronic subdural hematomas, but it is reasonable to reverse the effects …

Sequence Homology Between Hla-Bound Cytomegalovirus And Human Peptides: A Potential Trigger For Alloreactivity, Charles E. Hall, Vishal N. Koparde, Maximilian Jameson-Lee, Abdelrhman G. Elnasseh, Allison F. Scalora, David J. Kobulnicky, Myrna G. Serrano, Catherine H. Roberts, Gregory A. Buck, Michael C. Neale, Daniel E. Nixon, Amir A. Toor

Massey Cancer Center Publications

Human cytomegalovirus (hCMV) reactivation may often coincide with the development of graft-versus-host-disease (GVHD) in stem cell transplantation (SCT). Seventy seven SCT donor-recipient pairs (DRP) (HLA matched unrelated donor (MUD), n = 50; matched related donor (MRD), n = 27) underwent whole exome sequencing to identify single nucleotide polymorphisms (SNPs) generating alloreactive peptide libraries for each DRP (9-mer peptide-HLA complexes); Human CMV CROSS (Cross-Reactive Open Source Sequence) database was compiled from NCBI; HLA class I binding affinity for each DRPs HLA was calculated by NetMHCpan 2.8 and hCMV- derived 9-mers algorithmically compared to the alloreactive peptide-HLA complex libraries. Short consecutive (≥6) …

Increasing Role Of Nurse Practitioners In House Call Programs, Nengliang (Aaron) Yao, Karen Rose, Virginia Lebaron, Fabian Camacho, Peter Boling

School of Nursing Publications

Objectives

Residence-based primary care provides homebound frail patients with a care plan that is individually tailored to manage multiple chronic conditions and functional limitations using a variety of resources. We (1) examine the visit volume and Medicare payments for residence-based health care provided by nurse practitioners (NPs) in the Medicare fee-for-service environment; (2) compare NP's residential visits to those of internists and family physicians; and (3) compare the geographical service area of full-time house call NPs versus NPs who make nursing facility visits a major portion of their work.

Design

An observational study using secondary data.

Setting

Medicare Provider Utilization …

Safety And Effectiveness Of Propranolol In Severely Burned Patients: Systematic Review And Meta-Analysis, Ramiro Manzano-Nunez, Herney Andrés García-Perdomo, Paula Ferrada, Carlos Alberto Ordoñez Delgado, Diego Andrés Gomez, Jorge Esteban Foianini

Surgery Publications

Background

The objective of this systematic review was to determine the effectiveness and safety of propranolol compared to placebo or usual care for improving clinical relevant outcomes in severely burned patients (TBSA >20%).

Methods

Relevant articles from randomized controlled trials were identified by a literature search in MEDLINE, EMBASE, and CENTRAL. We included trials involving patients with a severe burn (>20% of total body surface area affected). Trials were eligible if they evaluated propranolol and compared to usual care or placebo. Two investigators independently assessed articles for inclusion and exclusion criteria and selected studies for the final analysis. We …

Pelvic Trauma: Wses Classification And Guidelines, Federico Coccolini, Philip F. Stahel, Giulia Montori, Walter Biffl, Tal M. Horer, Fausto Catena, Yoram Kluger, Ernest E. Moore, Andrew B. Peitzman, Rao Ivatury, Raul Coimbra, Gustavo Pereira Fraga, Bruno Pereira, Sandro Rizoli, Andrew Kirkpatrick, Ari Leppaniemi, Roberto Manfredi, Stefano Magnone, Osvaldo Chiara, Leonardo Solaini, Marco Ceresoli, Niccolò Allievi, Catherine Arvieux, George Velmahos, Zsolt Balogh, Noel Naidoo, Dieter Weber, Fikri Abu-Zidan, Massimo Sartelli, Luca Ansaloni

Surgery Publications

Complex pelvic injuries are among the most dangerous and deadly trauma related lesions. Different classification systems exist, some are based on the mechanism of injury, some on anatomic patterns and some are focusing on the resulting instability requiring operative fixation. The optimal treatment strategy, however, should keep into consideration the hemodynamic status, the anatomic impairment of pelvic ring function and the associated injuries. The management of pelvic trauma patients aims definitively to restore the homeostasis and the normal physiopathology associated to the mechanical stability of the pelvic ring. Thus the management of pelvic trauma must be multidisciplinary and should be …

Scedosporium Prolificans Septic Arthritis, Collier S. Pace, Jessica A. Frankenhoff, Jonathan E. Isaacs

Surgery Publications

Scedosporium prolificans is an emerging fungal pathogen that can cause significant morbidity, and even mortality, in both immunocompromised and immunocompetent patients. Approximately 10% of patients affected by this rare fungal pathogen present with septic osteomyelitis or arthritis. Overall, the rate of mortality is close to 50%, and several patients with orthopedic infections have required amputations.1 Our patient is a 59-year-old woman, with a history of rheumatoid arthritis requiring immunosuppressants, who presented with a 5-month history of right wrist pain and swelling. She described an oscillating course of swelling, erythema, and pain involving the dorsal aspect of her wrist that did …

Panamerican Trauma Society: The First Three Decades, Rao R. Ivatury, Michel Aboutanos

Surgery Publications

Panamerican Trauma Society was born 30 years ago with the mission of improving trauma care in the Americas by exchange of ideas and concepts and expanding knowledge of trauma and acute illness. The authors, immediate-past leaders of the organization, review the evolution of this assembly of diverse cultures and nationalities.

The Global Alliance For Infections In Surgery: Defining A Model For Antimicrobial Stewardship—Results From An International Cross-Sectional Survey, Massimo Sartelli, Francesco M. Labricciosa, Pamela Barbadoro, Leonardo Pagani, Luca Ansaloni, Adrian J. Brink, Jean Carlet, Ashish Khanna, Alain Chichom-Mefire, Federico Coccolini, Salomone Di Saverio, Addison K. May, Pierluigi Viale, Richard R. Watkins, Luigia Scudeller, Lilian M. Abbo, Fikri M. Abu-Zidan, Abdulrashid K. Adesunkanmi, Sara Al-Dahir, Majdi N. Al-Hasan, Halil Alis, Carlos Alves, André R. Araujo Da Silva, Goran Augustin, Miklosh Bala, Philip S. Barie, Marcelo A. Beltrán, Aneel Bhangu, Belefquih Bouchra, Stephen M. Brecher, Miguel A. Caínzos, Adrian Camacho-Ortiz, Marco Catani, Sujith J. Chandy, Asri Che Jusoh, Jill R. Cherry-Bukowiec, Osvaldo Chiara, Elif Colak, Oliver A. Cornely, Yunfeng Cui, Zaza Demetrashvili, Belinda De Simone, Jan J. De Waele, Sameer Dhingra, Francesco Di Marzo, Agron Dogjani, Gereltuya Dorj, Laurent Dortet, Therese M. Duane, Mutasim M. Elmangory, Mushira A. Enani, Paula Ferrada, J. Esteban Foianini, Mahir Gachabayov, Chinmay Gandhi, Wagih Mommtaz Ghnnam, Helen Giamarellou, Georgios Gkiokas, Harumi Gomi, Tatjana Goranovic, Ewen A. Griffiths, Rosio I. Guerra Gronerth, Julio C. Haidamus Monteiro, Timothy C. Hardcastle, Andreas Hecker, Adrien M. Hodonou, Orestis Ioannidis, Arda Isik, Katia A. Iskandar, Hossein S. Kafil, Souha S. Kanj, Lewis J. Kaplan, Garima Kapoor, Aleksandar R. Karamarkovic, Jakub Kenig, Ivan Kerschaever, Faryal Khamis, Vladimir Khokha, Ronald Kiguba, Hong B. Kim, Wen-Chien Ko, Kaoru Koike, Iryna Kozlovska, Anand Kumar, Leonel Lagunes, Rifat Latifi, Jae G. Lee, Young R. Lee, Ari Leppäniemi, Yousheng Li, Stephen Y. Liang, Warren Lowman, Gustavo M. Machain, Marc Maegele, Piotr Major, Sydney Malama, Ramiro Manzano-Nunez, Athanasios Marinis, Isidro Martinez Casas, Sanjay Marwah, Emilio Maseda, Michael E. Mcfarlane, Ziad Memish, Dominik Mertz, Cristian Mesina, Shyam K. Mishra, Ernest E. Moore, Akutu Munyika, Eleftherios Mylonakis, Lena Napolitano, Ionut Negoi, Milica D. Nestorovic, David P. Nicolau, Abdelkarim H. Omari, Carlos A. Ordonez, José-Artur Paiva, Narayan D. Pant, Jose G. Parreira, Michal Pędziwiatr, Bruno M. Pereira, Alfredo Ponce-De-Leon, Garyphallia Poulakou, Jacobus Preller, Céline Pulcini, Guntars Pupelis, Martha Quiodettis, Timothy M. Rawson, Tarcisio Reis, Miran Rems, Sandro Rizoli, Jason Roberts, Nuno Rocha Pereira, Jesús Rodríguez-Baño, Boris Sakakushev, James Sanders, Natalia Santos, Norio Sato, Robert G. Sawyer, Sandro Scarpelini, Loredana Scoccia, Nusrat Shafiq, Vishalkumar Shelat, Costi D. Sifri, Boonying Siribumrungwong, Kjetil Søreide, Rodolfo Soto, Hamilton P. De Souza, Peep Talving, Ngo Tat Trung, Jeffrey M. Tessier, Mario Tumbarello, Jan Ulrych, Selman Uranues, Harry Van Goor, Andras Vereczkei, Florian Wagenlehner, Yonghong Xiao, Kuo-Ching Yuan, Agnes Wechsler-Fördös, Jean-Ralph Zahar, Tanya L. Zakrison, Brian Zuckerbraun, Wietse P. Zuidema, Fausto Catena

Surgery Publications

Background

Antimicrobial Stewardship Programs (ASPs) have been promoted to optimize antimicrobial usage and patient outcomes, and to reduce the emergence of antimicrobial-resistant organisms. However, the best strategies for an ASP are not definitively established and are likely to vary based on local culture, policy, and routine clinical practice, and probably limited resources in middle-income countries. The aim of this study is to evaluate structures and resources of antimicrobial stewardship teams (ASTs) in surgical departments from different regions of the world.

Methods

A cross-sectional web-based survey was conducted in 2016 on 173 physicians who participated in the AGORA (Antimicrobials: A Global …

The Role Of Open Abdomen In Non-Trauma Patient: Wses Consensus Paper, Federico Coccolini, Giulia Montori, Marco Ceresoli, Fausto Catena, Ernest E. Moore, Rao Ivatury, Walter Biffl, Andrew Peitzman, Raul Coimbra, Sandro Rizoli, Yoram Kluger, Fikri M. Abu-Zidan, Massimo Sartelli, Marc De Moya, George Velmahos, Gustavo Pereira Fraga, Bruno M. Pereira, Ari Leppaniemi, Marja A. Boermeester, Andrew W. Kirkpatrick, Ron Maier, Miklosh Bala, Boris Sakakushev, Vladimir Khokha, Manu Malbrain, Vanni Agnoletti, Ignacio Martin-Loeches, Michael Sugrue, Salomone Di Saverio, Ewen Griffiths, Kjetil Soreide, John E. Mazuski, Addison K. May, Philippe Montravers, Rita Maria Melotti, Michele Pisano, Francesco Salvetti, Gianmariano Marchesi, Tino M. Valetti, Thomas Scalea, Osvaldo Chiara, Jeffry L. Kashuk, Luca Ansaloni

Surgery Publications

The open abdomen (OA) is defined as intentional decision to leave the fascial edges of the abdomen un-approximated after laparotomy (laparostomy). The abdominal contents are potentially exposed and therefore must be protected with a temporary coverage, which is referred to as temporal abdominal closure (TAC). OA use remains widely debated with many specific details deserving detailed assessment and clarification. To date, in patients with intra-abdominal emergencies, the OA has not been formally endorsed for routine utilization; although, utilization is seemingly increasing. Therefore, the World Society of Emergency Surgery (WSES), Abdominal Compartment Society (WSACS) and the Donegal Research Academy united a …

The Management Of Intra-Abdominal Infections From A Global Perspective: 2017 Wses Guidelines For Management Of Intra-Abdominal Infections, Massimo Sartelli, Alain Chichom-Mefire, Francesco M. Labricciosa, Timothy Hardcastle, Fikri M. Abu-Zidan, Abdulrashid K. Adesunkanmi, Luca Ansaloni, Miklosh Bala, Zsolt J. Balogh, Marcelo A. Beltrán, Offir Ben-Ishay, Walter L. Biffl, Arianna Birindelli, Miguel A. Cainzos, Gianbattista Catalini, Marco Ceresoli, Asri Che Jusoh, Osvaldo Chiara, Federico Coccolini, Raul Coimbra, Francesco Cortese, Zaza Demetrashvili, Salomone Di Saverio, Jose J. Diaz, Valery N. Egiev, Paula Ferrada, Gustavo P. Fraga, Wagih M. Ghnnam, Jae Gil Lee, Carlos A. Gomes, Andreas Hecker, Torsten Herzog, Jae Il Kim, Kenji Inaba, Arda Isik, Aleksandar Karamarkovic, Jeffry Kashuk, Vladimir Khokha, Andrew W. Kirkpatrick, Yoram Kluger, Kaoru Koike, Victor Y. Kong, Ari Leppaniemi, Gustavo M. Machain, Ronald V. Maier, Sanjay Marwah, Michael E. Mcfarlane, Giulia Montori, Ernest E. Moore, Ionut Negoi, Iyiade Olaoye, Abdelkarim H. Omari, Carlos A. Ordonez, Bruno M. Pereira, Gerson A. Pereira Júnior, Guntars Pupelis, Tarcisio Reis, Boris Sakakushev, Norio Sato, Helmut Ovia Lohse A. Segovia Lohse, Vishal G. Shelat, Kjetil Søreide, Waldemar Uhl, Jan Ulrych, Harry Van Goor, George C. Velmahos, Kuo-Ching Yuan, Imtiaz Wani, Dieter G. Weber, Sanoop K. Zachariah, Fausto Catena

Surgery Publications

Intra-abdominal infections (IAIs) are common surgical emergencies and have been reported as major contributors to non-trauma deaths in the emergency departments worldwide.

The cornerstones of effective treatment of IAIs are early recognition, adequate source control, and appropriate antimicrobial therapy. Prompt resuscitation of patients with ongoing sepsis is of utmost important.

In hospitals worldwide, non-acceptance of, or lack of access to, accessible evidence-based practices and guidelines result in overall poorer outcome of patients suffering IAIs.

The aim of this paper is to promote global standards of care in IAIs and update the 2013 WSES guidelines for management of intra-abdominal infections.

Splenic Trauma: Wses Classification And Guidelines For Adult And Pediatric Patients, Federico Coccolini, Giulia Montori, Fausto Catena, Yoram Kluger, Walter Biffl, Ernest E. Moore, Viktor Reva, Camilla Bing, Miklosh Bala, Paola Fugazzola, Hany Bahouth, Ingo Marzi, George Velmahos, Rao Ivatury, Kjetil Soreide, Tal Horer, Richard Ten Broek, Bruno M. Pereira, Gustavo P. Fraga, Kenji Inaba, Joseph Kashuk, Neil Parry, Peter T. Masiakos, Konstantinos S. Mylonas, Andrew Kirkpatrick, Fikri Abu-Zidan, Carlos Augusto Gomes, Simone Vasilij Benatti, Noel Naidoo, Francesco Salvetti, Stefano Maccatrozzo, Vanni Agnoletti, Emiliano Gamberini, Leonardo Solaini, Antonio Costanzo, Andrea Celotti, Matteo Tomasoni, Vladimir Khokha, Catherine Arvieux, Lena Napolitano, Lauri Handolin, Michele Pisano Pisano, Stefano Magnone, David A. Spain, Marc De Moya, Kimberly A. Davis, Nicola De Angelis, Ari Leppaniemi, Paula Ferrada, Rifat Latifi, David Costa Navarro, Yashuiro Otomo, Raul Coimbra, Ronald V. Maier, Frederick Moore, Sandro Rizoli, Boris Sakakushev, Joseph M. Galante, Osvaldo Chiara, Stefania Cimbanassi, Alain Chichom Mefire, Dieter Weber, Marco Ceresoli, Andrew B. Peitzman, Liban Wehlie, Massimo Sartelli, Salomone Di Saverio, Luca Ansaloni

Surgery Publications

Spleen injuries are among the most frequent trauma-related injuries. At present, they are classified according to the anatomy of the injury. The optimal treatment strategy, however, should keep into consideration the hemodynamic status, the anatomic derangement, and the associated injuries. The management of splenic trauma patients aims to restore the homeostasis and the normal physiopathology especially considering the modern tools for bleeding management. Thus, the management of splenic trauma should be ultimately multidisciplinary and based on the physiology of the patient, the anatomy of the injury, and the associated lesions. Lastly, as the management of adults and children must be …

Screening For Gynecologic Conditions With Pelvic Examination Us Preventive Services Task Force Recommendation Statement, Kirsten Bibbins-Domingo, David C. Grossman, Susan J. Curry, Michael J. Barry, Karina W. Davidson, Chyke A. Doubeni, John W. Epling Jr, Francisco A. R. García, Alex R. Kemper, Alex H. Krist, Ann E. Kurth, C. Seth Landefeld, Carol M. Mangione, William R. Phillips, Maureen G. Phipps, Michael Silverstein, Melissa Simon, Albert L. Siu, Chien-Wen Tseng

Internal Medicine Publications

IMPORTANCE Many conditions that can affect women's health are often evaluated through pelvic examination. Although the pelvic examination is a common part of the physical examination, it is unclear whether performing screening pelvic examinations in asymptomatic women has a significant effect on disease morbidity and mortality.

OBJECTIVE To issue a new US Preventive Services Task Force(USPSTF) recommendation on screening for gynecologic conditions with pelvic examination for conditions other than cervical cancer, gonorrhea, and chlamydia, for which the USPSTF has already made specific recommendations.

EVIDENCE REVIEW The USPSTF reviewed the evidence on the accuracy, benefits, and potential harms of performing screening …

Mutant P53 Establishes Targetable Tumor Dependency By Promoting Unscheduled Replication, Shilpa Singh, Catherine Vaughan, Rebecca Anne Frum, Steven R. Grossman, Sumitra Deb, Swati Palit Deb

Internal Medicine Publications

Gain-of-function (GOF) p53 mutations are observed frequently in most intractable human cancers and establish dependency for tumor maintenance and progression. While some of the genes induced by GOF p53 have been implicated in more rapid cell proliferation compared with p53-null cancer cells, the mechanism for dependency of tumor growth on mutant p53 is unknown. This report reveals a therapeutically targetable mechanism for GOF p53 dependency. We have shown that GOF p53 increases DNA replication origin firing, stabilizes replication forks, and promotes micronuclei formation, thus facilitating the proliferation of cells with genomic abnormalities. In contrast, absence or depletion of GOF p53 …

Reversal Of Hepatorenal Syndrome Type 1 With Terlipressin Plus Albumin Vs. Placebo Plus Albumin In A Pooled Analysis Of The Ot-0401 And Reverse Randomised Clinical Studies, A. J. Sanyal, T. D. Boyer, R. T. Frederick, F. Wong, L. Rossaro, V. Araya, H. E. Vargas, K. R. Reddy, S. C. Pappas, P. Teuber, S. Escalante, K. Jamil

Internal Medicine Publications

Background

The goal of hepatorenal syndrome type 1 (HRS-1) treatment is to improve renal function. Terlipressin, a synthetic vasopressin analogue, is a systemic vasoconstrictor used for the treatment of HRS-1, where it is available.

Aim

To compare the efficacy of terlipressin plus albumin vs. placebo plus albumin in patients with HRS-1.

Methods

Pooled patient-level data from two large phase 3, randomised, placebo-controlled studies were analysed for HRS reversal [serum creatinine (SCr) value ≤133 μmol/L], 90-day survival, need for renal replacement therapy and predictors of HRS reversal. Patients received intravenous terlipressin 1–2 mg every 6 hours plus albumin or placebo plus …

Epirubicin With Cyclophosphamide Followed By Docetaxel With Trastuzumab And Bevacizumab As Neoadjuvant Therapy For Her2-Positive Locally Advanced Breast Cancer Or As Adjuvant Therapy For Her2-Positive Pathologic Stage Iii Breast Cancer: A Phase Ii Trial Of The Nsabp Foundation Research Group, Fb-5, John W. Smith, Marc E. Buyse, Priya Rastogi, Charles E. Geyer Jr., Samuel A. Jacobs, Erica J. Patocskai, André Robidoux, Alison K. Conlin, Bilal Ansari, George P. Keogh, Philip J. Stella, Howard M. Gross, Raymond S. Lord, Jonathan A. Polikoff, Celine Mauquoi, Eleftherios P. Mamounas, Sandra M. Swain, Norman Wolmark

Massey Comprehensive Cancer Center Publications

Background

The purpose of this study was to determine the cardiac safety and clinical activity of trastuzumab and bevacizumab with docetaxel after epirubicin with cyclophosphamide (EC) in patients with HER2-positive locally advanced breast cancer (LABC) or pathologic stage 3 breast cancer (PS3BC).

Patients and Methods

Patients received every 3 week treatment with 4 cycles of EC (90/600 mg/m²) followed by 4 cycles of docetaxel (100 mg/m²). Targeted therapy with standard-dose trastuzumab with bevacizumab 15 mg/kg was given for a total of 1 year. Coprimary end points were (1) rate of cardiac events (CEs) in all patients …

The Clinical Features Of Paranoia In The 20th Century And Their Representation In Diagnostic Criteria From Dsm-Iii Through Dsm-5, Kenneth S. Kendler

Psychiatry Publications

This review traces, through psychiatric textbooks, the history of the Kraepelinian concept of paranoia in the 20th century and then relates the common reported symptoms and signs to the diagnostic criteria for paranoia/delusional disorder in DSM-III through DSM-5. Clinical descriptions of paranoia appearing in 10 textbooks, published 1899 to 1970, revealed 11 prominent symptoms and signs reported by 5 or more authors. Three symptoms (systematized delusions, minimal hallucinations, and prominent ideas of reference) and 2 signs (chronic course and minimal affective deterioration) were reported by 8 or 9 of the authors. Four textbook authors rejected the Kraepelinian concept of paranoia. …

State Of Harmonization Of 24 Serum Albumin Measurement Procedures And Implications For Medical Decisions, Lorin M. Bachmann, Min Yu, James C. Boyd, David E. Bruns, W. Greg Miller

Pathology Publications

BACKGROUND: Measurements of serum and plasma albumin are widely used in medicine, including as indicators of quality of patient care in renal dialysis centers.

METHODS: Pools were prepared from residual patient serum (n = 50) and heparin plasma (n = 48) from patients without renal disease, and serum from patients with kidney failure before hemodialysis (n = 53). Albumin was measured in all samples and in ERM-DA470k/IFCC reference material (RM) by 3 immunochemical, 9 bromcresol green (BCG), and 12 bromcresol purple (BCP) methods.

RESULTS: Two of 3 immunochemical procedures, 5 of 9 BCG, and 10 of 12 BCP methods recovered …

Quality Of Life In Chronic Pancreatitis Is Determined By Constant Pain, Disability/Unemployment, Current Smoking, And Associated Co-Morbidities, Jorge D. Machicado, Stephen T. Amann, Michelle A. Anderson, Judah Abberbock, Stuart Sherman, Darwin L. Conwell, Gregory A. Cote, Vikesh K. Singh, Michele D. Lewis, Samer Alkaade, Bimaljit S. Sandhu, Nalini M. Guda, Thiruvengadam Muniraj, Gong Tang, John Baillie, Randall E. Brand, Timothy B. Gardner, Andres Gelrud, Christopher E. Forsmark, Peter A. Banks, Adam Slivka, C. Mel Wilcox, David C. Whitcomb, Dhiraj Yadav

Pathology Publications

OBJECTIVES: Chronic pancreatitis (CP) has a profound independent effect on quality of life (QOL). Our aim was to identify factors that impact the QOL in CP patients.

METHODS: We used data on 1,024 CP patients enrolled in the three NAPS2 studies. Information on demographics, risk factors, co-morbidities, disease phenotype, and treatments was obtained from responses to structured questionnaires. Physical and mental component summary (PCS and MCS, respectively) scores generated using responses to the Short Form-12 (SF-12) survey were used to assess QOL at enrollment. Multivariable linear regression models determined independent predictors of QOL.

RESULTS: Mean PCS and MCS scores were …

Development And Validation Of Clinical Whole-Exome And Whole-Genome Sequencing For Detection Of Germline Variants In Inherited Disease, Madhuri Hegde, Avni Santani, Rong Mao, Andrea Ferreira-Gonzalez, Karen E. Weck, Karl V. Voelkerding

Pathology Publications

Context.-With the decrease in the cost of sequencing, the clinical testing paradigm has shifted from single gene to gene panel and now whole-exome and whole-genome sequencing. Clinical laboratories are rapidly implementing next-generation sequencing-based whole-exome and whole-genome sequencing. Because a large number of targets are covered by whole-exome and whole-genome sequencing, it is critical that a laboratory perform appropriate validation studies, develop a quality assurance and quality control program, and participate in proficiency testing.

Objective.-To provide recommendations for wholeexome and whole-genome sequencing assay design, validation, and implementation for the detection of germline variants associated in inherited disorders.

Data Sources.-An example of …

Development And Validation Of Targeted Next-Generation Sequencing Panels For Detection Of Germline Variants In Inherited Diseases., Avni Santani, Jill Murrell, Birgit Funke, Zhenming Yu, Madhuri Hegde, Rong Mao, Andrea Ferreira-Gonzalez, Karl V. Voelkerding, Karen E. Weck

Pathology Publications

Context.-The number of targeted next-generation sequencing (NGS) panels for genetic diseases offered by clinical laboratories is rapidly increasing. Before an NGS-based test is implemented in a clinical laboratory, appropriate validation studies are needed to determine the performance characteristics of the test.

Objective.-To provide examples of assay design and validation of targeted NGS gene panels for the detection of germline variants associated with inherited disorders.

Data Sources.-The approaches used by 2 clinical laboratories for the development and validation of targeted NGS gene panels are described. Important design and validation considerations are examined.

Conclusions.-Clinical laboratories must validate performance specifications of each test …

Hiv Induces Expression Of Complement Component C3 In Astrocytes By Nf-Κb-Dependent Activation Of Interleukin-6 Synthesis, Jadwiga Nitkiewicz, Alejandra Borjabad, Susan Morgello, Jacinta Murray, Wei Chao, Luni Emdad, Paul B. Fisher, Mary Jane Potash, David J. Volsky

Pathology Publications

Background

Abnormal activation of the complement system contributes to some central nervous system diseases but the role of complement in HIV-associated neurocognitive disorder (HAND) is unclear.

Methods

We used real-time PCR and immunohistochemistry to detect complement expression in postmortem brain tissue from HAND patients and controls. To further investigate the basis for viral induction of gene expression in the brain, we studied the effect of HIV on C3 expression by astrocytes, innate immune effector cells, and targets of HIV. Human fetal astrocytes (HFA) were infected with HIV in culture and cellular pathways and factors involved in signaling to C3 expression …

Evaluation Of The Angiotensin Ii Receptor Blocker Azilsartan Medoxomil In African-American Patients With Hypertension, Wallace Johnson, William B. White, Domenic Sica, George L. Bakris, Michael A. Weber, Alison Handley, Alfonso Perez, Charlie Cao, Stuart Kupfer, Elijah B. Saunders

Pathology Publications

The efficacy and safety of azilsartan medoxomil (AZL-M) were evaluated in African-American patients with hypertension in a 6-week, double-blind, randomized, placebo-controlled trial, for which the primary end point was change from baseline in 24-hour mean systolic blood pressure (BP). There were 413 patients, with a mean age of 52years, 57% women, and baseline 24-hour BP of 146/91mmHg. Treatment differences in 24-hour systolic BP between AZL-M 40mg and placebo (-5.0mmHg; 95% confidence interval, -8.0 to -2.0) and AZL-M 80mg and placebo (-7.8mmHg; 95% confidence interval, -10.7 to -4.9) were significant (P.001 vs placebo for both comparisons). Changes in the clinic BPs …