UPMC Physician Resources

Home » Gastroenterology

Archives for Gastroenterology

Experts to Present at Digestive Disease Week 2013

Posted by UPMC Physician Resources on Monday, May 20th 2013     

Experts from the Division of Gastroenterology, Hepatology, and Nutrition will have a strong presence at Digestive Disease Week 2013, with UPMC physicians and researchers making 16 oral presentations and 35 poster presentations. Preview of the key findings to be presented at the conference:

Uncontrolled Therapeutic Observations in IBD

Confocal Endomicroscopy, Enhanced Endscopy, and Other Emerging Technologies II

Upper GI Small Bowel Imaging: Polyps, Biopsies, Endoscopy Histology

Nutrient Digestion, Absorption, and Metabolism

Are you attending DDW?

To learn more about our clinical programs, research efforts, and fellowship opportunities, visit us at DDW booth 1533, May 18 to 21.

category: Gastroenterology, UPMC
tags: ,

UPMC Launches First-Ever Gastrointestinal Dermatology Clinic

Posted by andrewsj3 on Monday, May 13th 2013     
PITTSBURGH, May 13, 2013 – Today, UPMC opened the nation’s first-ever gastrointestinal dermatology clinic to provide coordinated care to inflammatory bowel disease (IBD) and celiac disease patients with associated dermatologic conditions.
Up to 30 percent of patients with IBD and celiac disease have cutaneous (skin-related) manifestations of their disease, yet until now there has not been a specialty clinic devoted specifically to these patients.
IBD, which affects as many as 1.4 million people in the U.S., primarily includes Crohn’s disease and ulcerative colitis. Crohn’s is a severe and chronic disease that causes inflammation, ulcers and bleeding in the digestive tract. Crohn’s often affects the end portion of the small intestine, but can affect any part of the gastrointestinal tract. Ulcerative colitis is another type of IBD which affects the colon (large intestine) and rectum. IBD differs from irritable bowel syndrome, which does not cause ulcers or inflammation and does not damage the bowel. Celiac disease is a digestive disorder which damages the small intestine and interferes with the absorption of nutrients from food. People with celiac cannot tolerate gluten, a protein found in wheat, barley and rye.
The clinic, located on the fifth floor of the Falk Medical Building in the Oakland area of Pittsburgh, will initially be open the first Monday of each month, though hours may change depending on demand. Patients must first be referred from UPMC-based gastroenterology departments.
“This is a novel service that we can provide to our patients,” said Lisa Grandinetti, M.D., assistant professor of dermatology at theUniversity of Pittsburgh and dermatologist at UPMC, who will be leading the new clinic. “We’re excited to open the first-ever specialty clinic to address the needs of IBD patients.”
Dermatologic manifestations of gastrointestinal (GI) diseases can occur as both the skin and the GI tract can be affected by the same conditions. Making the correct diagnosis of these conditions requires the ability of physicians to recognize the dermatological presentations of certain GI diseases. For example, dermatitis herpetiformis, or severely itchy small blisters on the elbows, knees and buttocks, is diagnostic for the GI condition known as celiac disease.
Other conditions that will be addressed by this clinic include, but are not limited to:

 

  • Erythema nodosum
  • Pyoderma gangrenosum
  • Aphthous ulcers/aphthous stomatitis
  • Dermatitis herpetiformis and celiac disease
  • TNFα associated psoriasiform dermatoses
  • Nutritional deficiency dermatoses

Dr. Grandinetti joined UPMC in 2009, and has since been receiving referrals from gastroenterologists for patients with IBD who have skin-related problems. Her interest in cutaneous manifestations of GI disease began after medical school, during her residency at the Cleveland Clinic.

“I saw firsthand how patients’ quality of life was significantly affected by their skin condition, often when their GI disease was under control,” noted Grandinetti. “With time, experience and a growing number of patients with cutaneous manifestations of GI diseases, I felt it was a good time to create a specialized clinic that would provide dermatologic and gastroenterologic coordinated care to patients with IBD and other GI issues.”

 

category: Gastroenterology, UPMC
tags: , , , , , ,

PSC Partners Seeking a Cure Announces Ninth Annual Conference

Posted by UPMC Physician Resources on Tuesday, February 26th 2013     

UPMC is proud to be a sponsorof the PSC Partners Seeking a Cure’s ninth annual conference for physicians and those affected by primary sclerosing cholangitis (PSC). The conference will be held April 26 to 28, 2013, at the DoubleTree Hotel & Suites, located in downtown Pittsburgh.

The purpose of the conference is to discuss the latest medical advances in the search for better treatments and a cure for PSC, and to offer PSC patients and caregivers the chance to network in an informal setting.

Highlights from UPMC experts include:

  • Natural History of PSC – Kapil Chopra, MD
  • New Advances in the Evaluation of Biliary Strictures – Adam Slivka, MD
  • PSC in Children: The Same Disease? – Benjamin Shneider, MD
  • Improving Quality of Life in PSC: Targeting Pain, Sleep, and Fatigue – Eva Szigethy, MD, PhD
  • Living-Donor Liver Transplant – Abhinav Humar, MD

To register and for more conference information, visit www.pscpartners.org/nextannual or email us at contact@pscpartners.org.

category: Abdominal Transplant, Gastroenterology, Liver Transplantation, Transplantation, UPMC
tags: , , , , , ,

National Experts Present: The Pittsburgh Gut Club Announces 2013 Schedule

Posted by UPMC Physician Resources on Thursday, January 10th 2013     

The Pittsburgh Gut Club is a gastroenterology education and networking series designed to bring novel and relevant subspecialty advancements to the Pittsburgh region. All gastroenterologists, interested physicians, and allied healthcare professionals are encouraged to attend.

Sponsored by
Division of Gastroenterology, Hepatology, and Nutrition
University of Pittsburgh School of Medicine
UPMC Center for Continuing Education in the Health Sciences

Course Director
Robert E. Schoen, MD, MPH
Professor of Medicine and Epidemiology
University of Pittsburgh School of Medicine

Schedule
All lectures are from 6:00 p.m. to 8:15 p.m. at The University Club, Pittsburgh, Pa.

February 21, 2013—Celiac Disease: From Soup to Nuts
Peter H.R. Green, MD
Professor of Clinical Medicine and Director, Celiac Disease Center
Division of Digestive and Liver Diseases
College of Physicians and Surgeons
Columbia University, New York, NY

March 7, 2013—Communicating the Risks and Benefits of Biologic Therapy for IBD
Corey A. Siegel, MD
Associate Professor of Medicine
The Dartmouth Institute for Health Policy and Clinical Practice
Director, Inflammatory Bowel Disease Center
Division of Gastroenterology and Hepatology
Dartmouth-Hitchcock Medical Center, Lebanon, NH

May 2, 2013—Hepatocellular Carcinoma: Epidemiology, Prevention via Treatment of Hepatitis, and Therapy
Hashem B. El-Serag, MD, MPH
Dan L. Duncan Professor of Medicine
Chief, Gastroenterology and Hepatology
Chief, Clinical Epidemiology and Outcomes
Baylor College of Medicine,  Houston, TX

Contact Information
For more information about The Pittsburgh Gut Club, including becoming a member, event registration, and associated fees, please contact:

Kimberly Luketic
Division of Gastrenterology, Hepatology, and Nutrition
200 Lothrop Street, Mezz. 2, C Wing
Pittsburgh, PA 15213
kil6@pitt.edu
 412.648.9241
 412.648.9378 (fax)

Continuing Medical Education
The University of Pittsburgh School of Medicine is accredited by the Accreditation Council for Continuing Medical Education for physicians. The University of Pittsburgh School of Medicine designates this educational activity for a maximum of 1.5 category one credits toward the AMA PRA Category 1 CreditsTM. Each physician should only claim credit commensurate with the extent of their participation in the activity. Other healthcare professionals are awarded .015 continuing education units (CEU’s) which are equal to 1.5 contact hours.

category: Gastroenterology, UPMC
tags: , , , ,

Transplant Effective in Treating Those With Severe Crohn’s Disease, UPMC Study Shows

Posted by UPMC Physician Resources on Monday, December 17th 2012     
PITTSBURGH, Dec. 17, 2012 – Patients suffering from severe Crohn’s disease who were no longer able to tolerate intravenous feedings were able to return to a normal oral diet and saw no clinical recurrences of the disease after undergoing intestinal or multivisceral transplants, according to a study of cases performed at UPMC over more than 20 years.
 
The study is the largest of its kind examining the efficacy of transplant in patients with end-stage Crohn’s disease. It was presented at the 2012 Advances in Inflammatory Bowel Diseases, the clinical and research conference of the Crohn’s and Colitis Foundation, in Hollywood, Fla., on Dec. 15.
 
“Intestinal transplantation was developed here at UPMC, and, as international leaders in this specialized surgery, we have a wealth of data that other centers don’t,” said Guilherme Costa, M.D., interim director, UPMC Intestinal Rehabilitation and Transplantation Center, who presented the study. “What that data show us is that intestinal and multivisceral transplant works to save the lives of those patients suffering from the most severe symptoms of Crohn’s disease.”
 
Crohn’s is a chronic bowel disease that can cause inflammation, ulcers and bleeding in the digestive tract. Patients suffering from a severe form of the disease often have irreversible intestinal failure and sometimes need to receive nutrition through a tube inserted into a vein, known as total perenteral nutrition (TPN). Patients unable to tolerate TPN are often referred for an intestinal transplant.
 
In the study, UPMC researchers looked at 309 adult patients who received intestinal and multivisceral transplants between 1990 and June 2012.  Of these, 57 had Crohn’s disease with irreversible intestinal failure, and all had failed TPN therapy with multiple line infections. Twenty-one percent, or 12, of these patients also required a liver transplant because they suffered from end-stage liver failure; 43 had just an intestinal transplant; and two patients had a modified multivisceral graft that included the stomach, duodenum, pancreas and intestine.
 
The study found the patient survival rate was 90 percent at one year, 74 percent at three years, 56 percent at five years, and 43 percent at 10 years. Inclusion of the donor liver was associated with better long-term survival outcome with a 10-year survival rate of 57 percent. All survivors achieved full nutritional autonomy, enjoying an unrestricted oral diet after transplant.
 
“The success we’ve seen in our patients is an indicator that transplant offers real hope to Crohn’s patients who have been debilitated by this disease,” Dr. Costa said.
category: Abdominal Transplant, Gastroenterology, Intestinal Transplantation, Transplantation, UPMC
tags: , , , , ,

Liver Disease and Liver Transplantation Update 2012

Posted by UPMC Physician Resources on Monday, November 19th 2012     

On Wednesday, November 28, 2012, this event will feature highlights from the annual meetings of American Association for the Study of Liver Diseases (AASLD); Digestive Diseases Week (DDW); and American Transplant Congress (ATC). 

UPMC experts will present on topics including:

  • Liver disease
  • Liver transplantation
  • Management of hepatocellular carcinoa
  • Hepatitis C

Course Director
Kapil B. Chopra, MD
Associate Professor of Medicine
Director of Hepatology
Medical Director, Liver Transplantation
Medical Director, Comprehensive Liver Program, UPMC Liver Pancreas Institute
Director, Transplant Hepatology Fellowship Program

Download the event program and registration information.

For more information, or to register, contact Brigid Tigano of the American Liver Foundation at 412-434-7040, or btigano@liverfoundation.org.

category: Gastroenterology, Liver Transplantation, Transplantation, UPMC

Genetic Link Between Pancreatitis and Alcohol Consumption

Posted by UPMC Physician Resources on Monday, November 12th 2012     
PITTSBURGH, Nov. 12, 2012 – A new study published online today in Nature Genetics reveals a genetic link between chronic pancreatitis and alcohol consumption.  Researchers from the University of Pittsburgh School of Medicine and more than 25 other health centers across the United States found a genetic variant on chromosome X near the claudin-2 gene (CLDN2) that predicts which men who are heavy drinkers are at high risk of developing chronic pancreatitis.
 
This finding enables doctors to identify people with early signs of pancreatitis or an attack of acute pancreatitis who are at very high risk for progressing to chronic pancreatitis, allowing them to take preventative action to slow the development of the disease, and give the pancreas a chance to heal. Once an individual develops pancreatitis it takes several years for the pancreas to deteriorate.
 
“The discovery that chronic pancreatitis has a genetic basis solves a major mystery about why some people develop chronic pancreatitis and others do not,” said David C. Whitcomb, M.D., professor of medicine, cell biology and physiology, and human genetics at the University of Pittsburgh School of Medicine and lead author of the report. “We also knew there was an unexpected higher risk of men developing pancreatitis with alcohol consumption, but until now we weren’t sure why. Our discovery of this new genetic variant on chromosome X helps explain this mystery as well.”
 
Over 100,000 Americans suffer from chronic pancreatitis, a progressive inflammatory disease characterized by abdominal pain and permanent damage to the pancreas. Most studies report excessive alcohol consumption as the major risk factor for adult-onset chronic pancreatitis. However, according to Dr. Whitcomb, who also is chief of the Division of Gastroenterology, Hepatology and Nutrition, only 3 percent of individuals who are alcoholics develop chronic pancreatitis, suggesting a pancreas-specific risk factor.
 
The study was conducted over 10 years and involved more than 2,000 patients, all of whom underwent DNA testing in a study funded by the National Institutes of Health. Researchers discovered that there was a common DNA variant on the X chromosome that is present in 26 percent of men without pancreatitis, but jumps to nearly 50 percent of men diagnosed with alcoholic pancreatitis. Women have two X chromosomes, so most women with the high-risk DNA variant on one X chromosome appear to be protected from alcoholic chronic pancreatitis by the other X chromosome, if it is normal. Men have one X chromosome and one Y chromosome, so if they inherit a high-risk X chromosome, there is no protection. 
 
The factor on chromosome X does not appear to cause pancreatitis, but if pancreatic injury occurs for any reason such as gallstone pancreatitis or abdominal trauma, it is more likely that the person will develop chronic pancreatitis – especially if they also drink alcohol. 
 
“This information is important because the high-risk chromosome can be identified in patients who drink and have early signs of pancreatic injury,” said Dhiraj Yadav, M.D., M.P.H., associate professor of medicine, Division of Gastroenterology, Hepatology and Nutrition at Pitt, and a co-investigator on the study. “If pancreatic injury and acute pancreatitis occur, patients must stop drinking immediately.”
 
Nationally, 16 percent of men drink alcohol at levels defined by the National Institute on Alcohol Abuse and Alcoholism as high risk. Twenty-six percent of these men who drink heavily are at high risk of chronic pancreatitis following pancreas injury. Only 10 percent of women drink alcohol at dangerous levels, and of these only 6 percent have the X chromosome variant on both X chromosomes. 
 
“Previous discoveries show that chronic pancreatitis without alcohol involvement has a strong genetic link. This helps to eliminate the previous stigma that patients with chronic pancreatitis must also be heavy drinkers,” added Dr. Whitcomb. “This study proves that there is a genetic element to the disease.”
 
Referrals of at-risk patients are welcome at UPMC and other large academic centers. The Pancreas Clinic within the UPMC Digestive Disorder Center is designed to evaluate patients using genetic and other data to provide treatment that is individualized to each patient. In addition to clinical care, the physician-scientists who staff this clinic are actively involved in teaching physicians and trainees the art and science of personalized medicine for chronic pancreatitis.  
 
Collaborators on this study include Bernie Devlin, Ph.D., Adam Slivka, M.D., Ph.D., Dhiraj Yadav, M.D., M.P.H., Randall E. Brand, M.D., Vijay Singh, M.D., Alyssa M Krasinskas, M.D., all of the University of Pittsburgh; Jill P. Smith, M.D., of Pennsylvania State – Hershey; John P. Neoptolemos, M.D., of the University of Liverpool; Markus M. Lerch, M.D., of the University of Greifswald; and others.
 
This research was supported by National Institutes of Health grants DK061451, DK054709, DK063922, MH057881, CA117926, UL1 RR024153 and UL1TR000005.
category: Gastroenterology, UPMC
tags: , , , , , ,

Pitt Researchers Pinpoint Peptide that Blocks Hepatitis C Virus Entry

Posted by andrewsj3 on Tuesday, July 31st 2012     
PITTSBURGH, July 31, 2012 – Researchers at the University of Pittsburgh’s Graduate School of Public Health (GSPH) have identified a specific peptide that may block the entry of the hepatitis C virus (HCV) into the liver, representing  a potential target for new drug development.
 
The results are available online now and will be published in the August 2012 print edition of Hepatology, the official journal of the American Association for the Study of Liver Disease. 
 
“Viral entry is a multi-step process, involving a number of host factors; therefore, these findings represent a promising target for new antiviral drugs,” said Tianyi Wang, Ph.D., associate professor, Department of Infectious Diseases and Microbiology, GSPH, and the study’s lead author.
 
Previous research indicates that human apolipoprotein E (apoE), which occurs naturally in the body, forms complexes with HCV, the scientists said. They constructed peptides, dubbed hEP, containing the portions of apoE to which other proteins and lipids typically bind.
 
In lab tests, they found that hEP blocked the virus from binding to liver cells, preventing infection. That suggests apoE is involved with HCV’s initial entry into the cells, Dr. Wang said. It’s possible that hEP thwarts infection because it competes with HCV for a cell surface receptor. 
 
In addition, researchers determined that the ability of hEP to block the virus appears to be dependent on the peptide’s length and sequence. Shorter versions could not stop infection, possibly because the shape of the proteins—and thus their binding ability—was altered.
 
“Our findings highlight the potential of developing peptides that mimic hEP as new hepatitis C viral inhibitors,” said Dr. Wang.
 
Worldwide, more than 170 million people are infected with the hepatitis C virus, which often is asymptomatic and can cause severe liver disease and liver cancer. There is no cure for HCV and no vaccine. Existing treatments are effective in only 40 percent to 80 percent of patients and can cause severe side effects.   
 
Despite the recent U.S. Food and Drug Administration approval of two new antiviral drugs designed to treat chronic HCV infection, patients may rapidly develop resistance. Much like current HIV therapies, successful treatment of HCV may involve multiple inhibitors of different targets, researchers said. 
 
“New antiviral drugs are urgently needed to treat HCV infection independently, or in combination with current therapies,” said Dr. Wang.
Collaborators on the studies include Shufeng Liu, Ph.D., and Kevin D. McCormick, M.S., Department of Infectious Diseases and Microbiology, GSPH, University of Pittsburgh; Wentao Zhao, Ph.D., and Daping Fan, Ph.D., Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina; and Ting Zhao, Department of Pathology, University of Pittsburgh School of Medicine.
 
The research was funded by grants R21AI083389, R01DK088787, and R21HL106325 from the National Institutes of Health.
category: Gastroenterology
tags: , , , , , , , , , ,

Pitt Researchers Developing Liver and Joint “Tissue Chips” to Better Predict Drug Safety

Posted by andrewsj3 on Friday, July 27th 2012     
PITTSBURGH, July 27, 2012 – Researchers at the University of Pittsburgh School of Medicine have been awarded federal grants to create micro-models of the liver and an arthritic joint as part of a national effort to build 3-D chips of cells and tissues that could  provide a more rapid and accurate method of predicting toxicity of experimental therapies, as well as foster greater understanding of myriad diseases.
 
Of the 17 projects being funded by the National Institutes of Health (NIH), two will be led by Pitt researchers and could receive more than $10 million over the next five years. NIH plans to commit up to $70 million over five years for the Tissue Chips for Drug Screening program, which was launched by its new National Center for Advancing Translational Sciences (NCATS). Other awardees include Johns Hopkins University, Harvard University and Duke University.
 
“Tissue chips could provide a more accurate and less expensive way of testing new drugs and reduce our reliance on animal studies, which often don’t reliably reflect toxicity profiles later seen during human testing,” noted Arthur S. Levine, M.D., senior vice chancellor for the health sciences and dean, Pitt School of Medicine. “It is terrific that our stellar scientists will be able to build two of these chips here and contribute to the evolution of drug testing.”
 
The Pitt projects are:
 
  • 3-D Micro-Liver: D. Lansing Taylor, Ph.D., Allegheny Foundation Professor of Computational and Systems Biology, and director, University of Pittsburgh Drug Discovery Institute, will lead a team at Pitt and Massachusetts General Hospital to create a three-dimensional microfluidic structure made entirely of human cells that will mimic the acinus, the smallest functional unit of the liver. The team also will develop a panel of sentinel “biosensor cells” that will indicate liver toxicity with exposure to different drugs.
  • The current gold standard of testing is not very gold,” Dr. Taylor said. “In humans, the liver plays a key role in processing drugs, and many experimental agents have failed in the late stages of human testing because preclinical studies didn’t predict their impact on the liver, along with other organs. This project aims to solve that problem so that we have greater success in drug discovery and development.”
  • 3-D Micro-Arthritic Joint System: Rocky Tuan, Ph.D., the Arthur J. Rooney Sr. Professor of Sports Medicine and executive vice chair for research, Department of Orthopaedic Surgery, will lead a team to create a tissue chip that includes stem cell-produced bone and cartilage cells that simulate joint surfaces to better understand how arthritis develops and how to prevent it.
  • This system will allow us to explore the effects of not only inflammatory molecules and the wear-and-tear of aging on the entire joint, but also mechanical injuries, such as a hit or a sprain, both immediately and over time in molecular detail, which is not feasible with existing techniques,” said Dr. Tuan, who also is director of the Center for Military Medicine Research, director of the Center for Cellular and Molecular Engineering in the Department of Orthopaedic Surgery, and co-director of the McGowan Institute for Regenerative Medicine.

According to NIH, the Tissue Chips program is the result of collaboration between NIH, the Defense Advanced Research Projects Agency (DARPA) and the U.S. Food and Drug Administration, and was established by the NIH’s Common Fund and the National Institute of Neurological Disorders and Stroke.

“Serious adverse effects and toxicity are major obstacles in the drug development process,” said Thomas R. Insel, M.D., NCATS acting director. “With innovative tools and methodologies, such as those developed by the Tissue Chips program, we may be able to accelerate the process by which we identify compounds likely to be safe in humans, saving time and money, and ultimately increasing the quality and number of therapies available for patients.”

Drs. Taylor and Tuan’s projects also will receive support from the University of Pittsburgh Clinical and Translational Science Institute.

category: Gastroenterology
tags: , , , , , , , ,

UPMC Clinches Top-Ten Spot on U.S. News & World Report Honor Roll of America’s Best Hospitals

Posted by andrewsj3 on Tuesday, July 17th 2012     

PITTSBURGH – UPMC rose to 10th place in U.S. News & World Report’s annual Honor Roll of America’s Best Hospitals – making it the highest-ranked medical center in Pennsylvania. U.S. News & World Report ranked UPMC first in the state and first in Pittsburgh.

“This national recognition is a testament to the skill and dedication of our physicians, nurses and staff and to the superb care they provide every day at UPMC. Our patients and our community have come to expect this level of excellence and we are committed to assuring we deliver. Our proudest achievements come when we make a difference in the lives and health of our patients,” said Elizabeth Concordia, executive vice president of UPMC and president of the Hospital and Community Services Division. “When patients require care, the choice is clear; the nation’s best care is here at UPMC.”

Nationally, UPMC is ranked for excellence in 15 adult specialty areas and is among the top 10 in nine specialty areas: Ear, Nose & Throat; Gastroenterology; Geriatrics; Gynecology; Nephrology; Neurology and Neurosurgery; Orthopaedics; Psychiatry and Pulmonology.

Last month, U.S. News named its 2012 Honor Roll of America’s Best Children’s Hospitals, on which Children’s Hospital of Pittsburgh of UPMC ranked ninth. This year marks UPMC’s 13th appearance on the Honor Roll. Last year, the list placed UPMC 12th nationally.

“A stellar ranking such as this validates what we know to be true – that UPMC is one of the very few academic medical centers in the nation that brings together the best in patient care, top-notch facilities and superior scientists,” added Steven Shapiro, M.D., senior vice president and chief medical and scientific officer, UPMC. “The exceptional clinical services that UPMC provides, fortified by Pitt’s academic research, work hand-in-hand to help us care for patients when they need us.”

About UPMC

UPMC is a $10 billion global health enterprise with more than 55,000 employees headquartered in Pittsburgh, Pa., and is transforming health care by integrating more than 20 hospitals, 400 doctors’ offices and outpatient sites, a health insurance services division, and international and commercial services. Affiliated with the University of Pittsburgh Schools of the Health Sciences, UPMC is redefining health care by using innovative science, technology and medicine to invent new models of accountable, cost-efficient and patient-centered care. For more information on how UPMC is taking medicine from where it is to where it needs to be, go to UPMC.com.

category: Gastroenterology, Geriatrics, Gynecology, Neurology, Neurosurgery, Orthopaedic Surgery, Otolaryngology, Psychiatry, Pulmonology, UPMC
tags: , , , , , , , , , , , , , , , ,
Page 1 of 4:1 2 3 4 »