A Novel Approach to Making Organ Transplants Successful

Study co-authors, from left: Zahi Fayad, PhD, Director of the Translational and Molecular Imaging Institute; and Willem J.M. Mulder, PhD, Professor of Radiology, and Oncological Sciences.

The nearly 35,000 individuals who receive organ transplants each year in the United States face a harsh reality: the immunosuppressive drugs they must take to maintain organ survival also weaken the immune system, breaking down the body’s critical defenses against cancer, infection, and more. Researchers at the Icahn School of Medicine at Mount Sinai recently developed an innovative type of immunotherapy based on nanotechnology that they hope will address this conundrum. Their findings, published in the November 6, 2018, issue of Immunity, have demonstrated the technology’s feasibility of long-term organ acceptance in mice.

“This is a whole new approach to programming the immune system, not just another small molecule drug that’s going to help with organ transplantation,” says Zahi Fayad, PhD, Director of the Icahn School of Medicine at Mount Sinai’s Translational and Molecular Imaging Institute, which conducted the work. Dr. Fayad is also Professor of Diagnostic, Molecular, and Interventional Radiology, and Medicine (Cardiology). “Because of the many problems this approach addresses—the risk of rejection, the shortage of organs for transplant, the cost of these procedures—we believe it can be transformative for the organ transplant field.”

Jordi Ochando, PhD

The immunotherapy works by regulating innate immune memory, or trained immunity, which the investigators found to play a central role in organ rejection. In trained immunity, immune cells known as myeloid cells initiate the body’s immune system response by activating T cells, which then attack the transplanted organ.

“By inhibiting trained immunity, we prevent activation of the myeloid cells and their subsequent activation of T cells,” says Jordi Ochando, PhD, the study’s co-senior author, who is Assistant Professor of Medicine (Nephrology), Oncological Sciences, and Pathology at the Icahn School of Medicine. “This novel technology preserves the normal function of the T cells, which is to protect the body against cancer and infections.”

Identifying trained immunity as a target enabled the Mount Sinai scientists to focus on a signaling pathway known as mammalian target of rapamycin (mTOR), which regulates immune cell metabolism. The team developed an injectable nanoimmunotherapy based on high-density lipoprotein (HDL) nanomaterials and the existing mTOR inhibitor rapamycin.

“These nanomaterials essentially deliver the rapamycin to the myeloid cells, and that changes the metabolic state of the cells and prevents their activation,” says co-senior author Willem J.M. Mulder, PhD, Professor of Radiology, and Oncological Sciences at Icahn School of Medicine, and Director of the Nanomedicine Program. The absence of myeloid cell and T cell activation, Dr. Mulder points out, could drastically reduce the need for transplant patients to take lifelong immunosuppressive medicines to prevent graft rejection.

A Rare Bladder Condition, and in Need of a Kidney Transplant: Little Lexi’s Extraordinary Medical Journey

Lexi Isler got a kiss from her father, Luther, before the kidney transplant surgery in January.

In 2009, when a prenatal ultrasound showed an abnormal kidney, Luther and Ashley Isler knew that their daughter, Lexi, would be born with a urinary problem. What they did not expect, however, was that Lexi would also be born without a bladder, a condition known as bladder agenesis that has only 20 known survivors worldwide.

Today, 8-year-old Lexi is among those remarkable survivors as she continues an extraordinary medical journey supported by her loving family and an interdisciplinary team of Mount Sinai physicians that has included pediatric urologists and nephrologists, and transplant surgeons, along with nurses and countless other caring staff over the years.

When Lexi was 2 years old, doctors at Mount Sinai Kravis Children’s Hospital confirmed by magnetic resonance imaging that urine had been backing up into her kidney—because she did not have a bladder. While she was in diapers, not having a bladder was not immediately obvious, but as she grew older, Lexi would need a way to both hold and pass urine. Meanwhile, her kidneys—damaged by her urinary outflow anatomy—had been steadily deteriorating and doctors realized that she would eventually need a kidney transplant.

Lexi’s urology and pediatric doctors formed a close team to strategize about her case from the earliest stages. “Long before a transplant, our team first had to think about how to make a bladder and how to get it to work,” says Jeffrey M. Saland, MD, Chief of Pediatric Nephrology and Hypertension at Mount Sinai Kravis Children’s Hospital and Medical Director of the Pediatric Kidney Transplant Service.

When Lexi was 5 years old, Jeffrey A. Stock, MD, Associate Professor of Urology, and Pediatrics, Icahn School of Medicine at Mount Sinai, and Chief of the Division of Pediatric Urology at Mount Sinai Kravis Children’s Hospital, performed the complex, six-hour surgery to create an artificial bladder.

“We removed part of her colon and connected the ends to create a bowel pouch that functioned as a bladder,” says Dr. Stock. “Then, we used her appendix to create a urethra to drain urine from the neobladder.” The neobladder can store, but not empty, urine so Lexi has learned to use a catheter in the bathroom to empty her new bladder. The neobladder procedure is rare. Dr. Stock, who specializes in the surgical reconstruction of genitourinary birth defects, has done only four such procedures in his 25 years of practice.

By January 2018, Lexi’s kidney function was so compromised that at one point, she was unresponsive for days. The situation remained critical all year with very little improvement, and in December 2018, the need for a kidney transplant could not be deferred. Fortunately for Lexi, when she was 3, her father had been identified as a match for her. “It was an easy decision,” says Mr. Isler. “I felt blessed that I was a match.”

Victoria Caselnova, RN, BSN, left, and Stacey Brooks, RN, BSN, with a smiling Lexi Isler on the day she was discharged from the hospital.

In January 2019, as Lexi was about to go into kidney failure, surgeons from the Recanati/Miller Transplantation Institute at Mount Sinai performed the transplant using her dad’s kidney. “We had all of our firepower available,” says Ron Shapiro, MD, Professor of Surgery, and Surgical Director of the Kidney and Pancreas Transplant Program, referring to the expert team of surgeons involved with the transplant and the bladder creation. A smiling Lexi was discharged after spending nine days in the hospital for the transplant surgery.

Still, says Dr. Saland, “This is a work in progress. Lexi remains at higher risk for urinary tract infections and we’ll need to make ongoing adjustments for drainage as well as in her anti-rejection medications. But at Mount Sinai, we believe we have all the expertise and resources we need to treat all aspects of Lexi’s condition.”

“I have the utmost respect for the doctors and nurses at Mount Sinai,” says Ms. Isler. “They all treated Lexi with so much respect and love. The nurses even came to her bedside when their shifts were over to paint with her.”

Despite periodic hospital stays, Lexi is happy and back at school, facing her health challenges with grace and an amazingly positive attitude for a girl her age, says Ms. Isler. Lexi recently found the courage to stand before her classmates and tell them about the condition she was born with and how it was treated. “Her classmates have been very supportive, and they don’t treat her like she’s different,” says Ms. Isler.

At home, the child who had been taking dance classes since the age of 2 has newfound energy and dances around the house with a lack of inhibition, Mr. Isler says. “With a lot of support, our goal is to enable Lexi to live a long, happy, and healthy life,” says Dr. Stock.

To learn more about organ donation, visit www.LiveOnNY.org.

What Are the Early Signs of Hearing Loss in Babies?

Hearing is critically important for a baby and is closely linked to language development in the first few years of life. Because of this, it is important to identify potential hearing loss as soon as possible so that early intervention can be arranged. Maura Cosetti, MD, Director, Otology/Neurotology, Mount Sinai Downtown, Associate Director, Ear Institute, New York Eye and Ear Infirmary of Mount Sinai (NYEE), and  Aldo Londino, MD,  Assistant Professor of Pediatric Otolaryngology at the Mount Sinai Health System and Chief of the Division of Pediatric Otolaryngology at the Mount Sinai Kravis Children’s Hospital, detail what parents need to know about spotting—and addressing—hearing loss in babies.

How common is pediatric hearing loss and what are the causes?

Approximately two to three infants per 1,000 are born deaf or with severe to profound hearing loss. Causes range from hereditary hearing loss to improper development of the inner ear. Hearing loss can also occur after birth and may be related to infections or other medical problems that occurred around the time of delivery.

How and when are babies tested for hearing loss?

All newborns are given a mandatory hearing test before leaving the hospital. This non-invasive screening helps identify babies who are deaf or hard of hearing by monitoring for either an ear or a brain response to a sound.

What does it mean if my baby “fails” the newborn hearing screening? 

There are many reasons that your baby may have failed the newborn screening test.  Because it is a screening, failing does not always mean your child has permanent or severe hearing loss. It is important to have a trained audiologist perform additional testing to assess your baby’s condition.

If hearing loss—whether permanent or temporary—is suspected, follow up testing with a pediatric audiologist is necessary to determine the amount of hearing loss and the appropriate interventions.  Interventions may range from observation, to hearing aids, and even cochlear implant evaluations.

My baby did not fail the newborn hearing screening. What are the signs of potential hearing loss as my child develops?

Signs and symptoms of hearing loss in babies vary, as children may reach milestones at different ages. However, the earlier hearing loss is diagnosed, the earlier it can be treated and the better the outcome for your child’s future development. Be aware of the following age-related guidelines to help gauge your child’s progress:

From birth to three months, your baby should:
  • React to loud sounds with a startle reflex
  • Turn their head to you when you speak
  • Be awakened by loud voices and sounds
From three to six months, your baby should:
  • Look or turn toward a new sound
  • Respond to “no” and changes in tone of voice
  • Begin to produce their own voice
From 6 to 10 months, your baby should:
  • Respond to their own name
  • Understand words for common items or phrases (mama, dada, milk, bottle, bye-bye)
  • Make babbling sounds
From 10 to 15 months, your baby should:
  • Look at familiar objects or point to people when asked to do so
  • Say simple words and sounds; may use a few single words meaningfully
  • Enjoy games like peek-a-boo and pat-a-cake

What steps should I take if my baby begins exhibiting signs of hearing loss?

If you feel that your baby is not meeting their developmental milestones to speak, play, or communicate, you should ask your pediatrician for a referral to a pediatric ear, nose, and throat specialist. Since hearing loss can affect your child’s ability to develop speech, language, and communication skills, it is of the utmost importance that your child receive appropriate services and treatment, which may include hearing aids, as soon as possible.

Maura K. Cosetti, MD

Maura K. Cosetti, MD

Director, Otology/Neurotology, Mount Sinai Downtown and Associate Director, Ear Institute

Dr. Cosetti specializes in the diagnosis and treatment of pediatric and adult hearing disorders, facial nerve disorders, and other complex conditions, as well as cochlear implantation, endoscopic ear surgery, and skull base surgery.

Aldo Londino, MD

Aldo Londino, MD

Assistant Professor of Pediatric Otolaryngology and Chief, Division of Pediatric Otolaryngology, Mount Sinai Kravis Children’s Hospital.

Dr. Londino specializes in the treatment of children with complex medical problems of the ears, nose, and throat.

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The Ear Institute at NYEE houses a team of highly specialized and skilled ear, nose and throat physicians, otologists-neurotologists, audiologists, speech-language pathologists, early intervention specialists, and other professionals who work collaboratively and are backed by the full services and resources of the Mount Sinai Health System. 

How to Manage Seasonal Allergies

As winter comes to an end, we look toward the warmth of spring, the budding of flowers, and the greening of grasses and trees. Unfortunately for some, the season also signals the onset of seasonal allergies. Also called “hay fever,” the condition brings about itchy and watery eyes, nasal congestion, sore throat, malaise, and rash. Joseph Feldman, MD, FACEP, an emergency physician, and Medical Director for Mount Sinai Urgent Care, explains what you can do to manage your allergy symptoms and when you should consult a physician.

What should I do to combat seasonal allergies?

Seasonal allergies can be caused by pollen from flowers, grasses, weeds, and even mold spores. The first-line treatment is to avoid pollen where and whenever possible. This is best accomplished by keeping the windows closed in your home and car and using the air conditioner.  It is important to frequently clean the filters of the air-conditioning unit to wash away the offending pollen.

It is also helpful to exercise indoors and to shower when entering your home, to wash away the pollen that may be on your body and clothes from being outdoors. Using nasal rinses, like the neti pot, may also help to eliminate the irritants and counteract the symptoms they cause. Drinking lots of fluids and remaining well hydrated will also improve symptoms.

What medications can I take to lesson my symptoms?

The three main types of medications used to treat allergies are antihistamines, decongestants, and steroids. These medications are available over the counter in the form of pills, nasal sprays, eye drops, and ointments.

It can be difficult to choose which medication is right for you. Remember, the correct medication depends on your symptoms, not a brand.

  • Look for products containing a nondrowsy antihistamine if you suffer from sneezing or a runny nose.
  • Use a combination of an antihistamine and a decongestant if your sinuses are stuffed up. NOTE: Hypertensive patients should not use decongestants as it can raise blood pressure.
  • A steroid nasal spray can be used on its own or in conjunction with an antihistamine nasal spray to quickly clear the nasal passages. Be sure to do a saline rinse prior to using a nasal spray in order to wash away pollen and ensure better penetration of the medication.
  • Itchy, watery eyes can be treated by trying artificial tears to wash away the offending pollen or antihistamine eye drops can be prescribed.

Pregnant women and small children should always consult a physician before using any medication.

When should I consult a physician about my allergies?

Seasonal allergies can occur at any time in life and can wax and wane in occurrence and severity. If your over-the-counter allergy medication is no longer working you can see your Primary Care Provider or visit one of our conveniently located Urgent Care Centers.  If necessary, you can be referred to an allergist.

Symptomatic treatment in combination with prescribed medications can successfully treat most situations.  An allergist can conduct skin testing to see what specific substances you are allergic to.  If so, arrangements can be made for you  to receive allergy injections that can help desensitize you to the offending allergens.  However, this takes time and does not afford immediate relief of symptoms.

You can start taking preventative measures and your medications as soon as you start being symptomatic.

At Mount Sinai Urgent Care, we want your experience to be fast, easy, and as stress-free as possible. You can walk in without an appointment during our convenient daytime, evening, and weekend hours. Our physicians will prescribe medication and, if needed, obtain an allergist referral. We accept all insurance, many without a co-pay.

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How to Cope With Difficulty Swallowing

Difficulty swallowing (medically termed dysphagia), can occur in both children and adults. Diana N. Kirke, MD, MPhil, Assistant Professor of Otolaryngology – Head and Neck Surgery at the Icahn School of Medicine at Mount Sinai and a laryngologist/head and neck surgeon at The Grabscheid Voice and Swallowing Center, explains the condition and answers some of the most frequently asked questions.

What are the symptoms of dysphagia and what causes the condition?

People suffering from dysphagia may experience symptoms such as gagging or choking, excessive throat clearing, food or liquid “going down the wrong way,” increased eating time, unexplained weight loss, coughing during or after eating/drinking, and/or painful swallowing.

Various medical issues can lead to this condition. However, dysphagia is more common in the elderly and in those with neurological conditions such as stroke, brain injury, and dementia.

When should I see a health care provider about difficulty swallowing?

Acute dysphagia, in which symptoms persist for 24 hours, requires immediate evaluation in the emergency room, as it may be related to food impaction or an ingested foreign body. Symptoms of difficulty swallowing that are present for more than 10 days should be assessed in an outpatient office setting.

What can I expect during my office visit?

Your physician will perform a complete head and neck examination to assess your upper aerodigestive system, which includes the mouth, throat, and windpipe. A fiber-optic nasal endoscopy may also be conducted. Using a topical anesthetic, a fiber-optic endoscope will be passed through your nostril to examine the nasal cavity and throat. This procedure generally does not last longer than one minute. An assessment by a speech therapist will also be undertaken either at the same visit or at a later visit. The speech therapist will assist in gathering diagnostic information regarding the swallow and may provide swallow therapy techniques in order to overcome swallowing difficulty.

Will I need further evaluations?

Depending on your initial assessment, the physician and the speech therapist may perform the following in-office or out-of-office swallow evaluations:

  • Using local anesthetic, a transnasal esophagoscopy may be performed to view the esophagus. During the procedure, a small camera is passed through the nostril.
  • To view the throat before and after drinking, a static endoscopic evaluation of swallow (SEES) may be performed. During this procedure, a rigid camera is passed into the mouth for observation. SEES can also be used to assess vocal cord vibration.
  • Speaking and swallowing tasks may be examined during a flexible endoscopic examination of swallow which is performed using a fiber-optic endoscope.
  • To assess the functionality of all phases of swallowing, a modified barium swallow may be performed. During this fluoroscopic X-ray exam, you will ingest barium-containing liquids and coated food. The procedure will also assess whether any food or liquid is entering into the lungs.

What is swallowing therapy?

Following a complete assessment by your treating physician and speech therapist, you may be prescribed swallowing therapy. This may entail dietary modifications and/or exercises that aim to coordinate and strengthen the swallowing muscles. Generally a treatment plan is prescribed and you will be reassessed again at a later date.

Will I need surgery?

It depends. Some cases of swallowing dysfunction, such as Zenker’s diverticulum, may be amenable to an in-office or surgical procedure. In other cases, an aesthetic neurotoxin like Botox® can be injected in the office to weaken the swallowing muscles and allow food to pass more easily. Botox is used to treat dysphagia-causing conditions such as cricopharyngeal spasm—in which throat muscles spasm uncontrollably— or esophageal web—in which thin membranes occur along the esophagus.

Should I wait to see if my swallowing problem resolves?

No. All dysphagia complaints should be assessed and you should see a doctor immediately if your symptoms are affecting your ability to consume food and drink. If you are able to eat and drink normally, you can observe your symptoms at home for up to 10 days before seeing a physician.

Diana N. Kirke, MD, MPhil

Diana N. Kirke, MD, MPhil

is an otolaryngologist-head and neck surgeon at Mount Sinai Doctors, 5 East 98th Street, and laryngologist at The Grabscheid Voice and Swallowing Center of Mount Sinai. Dr. Kirke cares for patients with voice, airway and swallowing disorders, head and neck cancers and general ear, nose and throat diseases.

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$4 Million Grant for Study of Sickle Cell Treatment

Jeffrey Glassberg, MD, left, administered a lung-function test to Eric Gay, a participant in the clinical trial.

An inhaled treatment that might improve lung function— and reduce the painful symptoms—of patients with sickle cell disease (SCD) is being studied in a clinical trial funded by a $4 million grant from the National Institutes of Health awarded to researchers at the Icahn School of Medicine at Mount Sinai.

“Inhaled corticosteroids, a well-established treatment for asthma, offer a creative new approach to treating sickle cell disease, with the potential to dramatically improve patient outcomes,” says Jeffrey Glassberg, MD, principal investigator of the study, and Associate Professor of Emergency Medicine, and Medicine (Hematology and Medical Oncology). SCD affects about 100,000 people in the United States and is more prevalent in certain ethnic groups, such as African Americans and Hispanics.

he inherited disease is caused by a mutation in hemoglobin, a protein inside red blood cells that carries oxygen from the lungs to the rest of the body. In SCD, abnormal hemoglobin forms long rods and distorts red blood cells into a sickle shape. The repeated damage to red cells causes the blood to become inflamed and sticky, causing pain, infections, stroke, and potentially, early death. The only organs in the body that can reverse sickling are the lungs, but they are highly inflamed in SCD. That is why researchers have proposed using inhaled steroids as a treatment.

“We hypothesize that if patients take an asthma medicine that reduces inflammation in the lungs, it might improve their ability to put oxygen into their blood and make their sickle cell better,” says Dr. Glassberg, Director of the Comprehensive Program for Sickle Cell Disease at the Icahn School of Medicine. The phase II trial—Inhaled Mometasone to Promote Reduction in Vaso-occlusive Event (IMPROVE 2)—is seeking to recruit 80 patients who have sickle cell disease but do not have asthma. They will be randomized, with one group receiving a placebo and the other receiving an inhaled treatment of the steroid mometasone furoate once a day for 48 weeks. The dose will be low, 220 micrograms, to avoid side effects associated with steroids, such as weight gain or bone disorders.

The primary outcome studied will be the level of a biomarker called soluble vascular cell adhesion molecule (sVCAM). “This is something that you measure in the blood, and it correlates very well with how bad somebody’s sickle cell disease is at the time,” says Dr. Glassberg. “The sVCAM level goes up when they are sick, and it goes back down when they get better.” Patients will also keep a daily diary of their pain and quality of life, and return regularly for tests of lung function.

A prior study, IMPROVE 1, established the feasibility of the current trial, with results published in March 2017 in the American Journal of Hematology. It involved 52 patients, who took the inhaled treatment for 16 weeks. Sickle cell symptoms tend to be seasonal, with some patients reporting more pain in colder months, so Dr. Glassberg says the longer IMPROVE 2 study will provide a broader understanding of the treatment. His group is seeking to enroll 20 people a year and to complete the study in June 2023.

Dr. Glassberg sees a future role for inhaled steroids as part of a drug “cocktail,” along with drugs like hydroxyurea that interfere with sickling. A low-dose inhaled steroid treatment would work in concert with these drugs, improving the flow of oxygenated blood. “This is especially appealing because inhaled steroids are inexpensive, widely available, and do not require sophisticated equipment, so they can be used anywhere in the world,” Dr. Glassberg says. “I think this treatment has the potential for a big health impact.”

For information about enrollment in the clinical trial, call 212-241-3650.

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