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Balanced Approaches to Acute and Chronic Pain – Conference

Friday, September 21st, 2018

Sept. 21-23, 2018, Sheraton Atlanta Hotel. For more information, visit Southern Pain Society.

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Innovations in Interventional Pulmonology

Thursday, November 30th, 2017

By Venk Lakshminarayanan, MD, Ph.D.

Traditional bronchoscopy is a procedure allowing direct visualization of the tracheobronchial trees of the airway. Historically, the main types of bronchoscopy are rigid and flexible. Flexible bronchoscopy allows for visualization of the lumen, mucosa of the trachea, proximal airways and segmental airways to the third generation of segmental bronchi.

This device allowed for focused obtainment of specimens as part of the evaluation for infectious, malignant or alternative etiologies. Additionally, it is used to diagnose or treat abnormalities within or adjacent to these airways.

Extrinsic compression of the airway from a mass can be assessed as well as direct sampling of peribronchial masses with transbronchial needle aspiration (TBNA). With the advent and initiation of fluoroscopic guidance, there was increased sensitivity in the ability to biopsy peripheral lung lesions which were not directly visualized in an airway.

Bronchoscopy has evolved greatly over the past decade with advances in endoscopic and pathological technologies. Traditional use of fiberoptic bronchoscopy limited tissue sampling to larger (> 2 cm) and more central lesions. With the development of electromagnetic navigation bronchoscopy (ENB) and radial probe ultrasound guidance, we can now access and obtain diagnostic tissue from the peripheral lung nodules with greater sensitivity and at smaller sizes.

Figure 1 - Interventional Pulmonology

Figure 1: Right lower paratracheal lymph node 4R in a patient with a right upper lobe lung mass right mediastinal lymph adenopathy. The white arrow indicates the lymph node. The blue arrow notes the lower border of the azygous vein. Samples taken by L-EBUS were consistent with non-small cell lung cancer. This was consistent with the previously biopsied right upper lobe mass.

These procedures enable the experienced interventionalist to access most mediastinal lymph nodes to provide a complete staging procedure. ENB, which combines bronchoscopy with electromagnetic navigation, allows the interventional bronchoscopist to sample significantly smaller and more peripheral lesions. The use of a linear probe EBUS (L-EBUS) allows for sampling of enlarged mediastinal, hilar lymph nodes or masses, potentially eliminating the need for mediastinoscopy. Endobronchial ultrasound-guided TBNA is a less-invasive alternative in staging of lung cancer in addition to diagnosis.

The presence of lymph node metastasis remains one of the most adverse factors for prognosis in non-small cell lung cancer (NSCLC). The presence of mediastinal lymph node involvement may indicate the presence of stage IIIA or IIIB, thereby suggesting either inoperability or the need for adjuvant chemotherapy and/or radiotherapy.1

Sampling Lymph Nodes and Peripheral Modules

There are three techniques involved in interventional pulmonology in the diagnosis, staging and treatment of potential lung cancers: endobronchial ultrasound (EBUS), electromagnetic navigational bronchoscopy (EMB) and photodynamic therapy (PDT).

Endobronchial ultrasound (EBUS) is a bronchoscopic technique that uses ultrasound to visualize structures adjacent to the wall of the bronchus. It allows for rapid pathologic staging of mediastinal and hilar lymph nodes,1 as well as for pathologic evaluation of nodal disease, which may be seen during radiographic staging.

EBUS is different than endoscopic ultrasound (EUS). While both visualize and guide sampling of lymph nodes, EBUS is performed during bronchoscopy for mediastinal lymphadenopathy. There are two types of EBUS: radial probe EBUS (RP-EBUS) and linear probe EBUS (L-EBUS). The RP-EBUS provides 360-degree circumferential images of the airway wall and surrounding structures.

Figure 2

Figure 2: Electromagnetic Navigational Bronchoscopy (ENB). Image 2A demonstrates the 3-D reconstructing virtual image of the mass following CT scan. Images 2B, 2C and 2D demonstrate the left lower lobe mass by CT imaging. Figure 2E demonstrates the ENB-generated directed pathway to the nodule.

A major advantage of RP-EBUS is its ability to visualize the layers of the airway wall in detail. In contrast, the L-EBUS provides a view that is parallel to the shaft of the bronchoscope with view 30 degrees forward of oblique. Color flow and Doppler features permit identification of vascular, ductal, and cystic structures. The major advantage of L-EBUS is its ability to guide real-time sampling. Coupled with rapid onsite evaluation (ROSE) by a cytopathologist allows for expedited pathologic staging of lymph node. Figure 1 demonstrates a right lower paratracheal lymph node (4R station) seen with an L-EBUS probe, in a patient with a peripheral lung mass with associated adenopathy.

Another area of interventional pulmonology that has rapidly developed recently is electromagnetic navigation bronchoscopy (ENB). ENB allows for more accurate targeting of peripheral lung lesions for biopsy over traditional bronchoscopy with fluoroscopy.The combined modalities of ENB and RP-EBUS can increase the sensitivity of diagnostic yields, especially with peripheral lung nodules, which is of great advantage for nodules as small as 10 mm.

Figure 2 demonstrates a left lower lobe lung nodule biopsied under ENB. Coupled with L-EBUS, this two-staged procedure allowed for diagnostic sampling of the peripheral lung mass and mediastinal lymph nodes. This allowed pathologic staging of this lung mass, and the mediastinal adenopathy results in an expedited diagnostic pathway with increased sensitivity in lung cancer staging. The goal of these combined modalities is to provide a greater patient experience and reduce time to initiate treatment.

Figure 3

Figure 3A: the initial obstructing right main-stem mass consistent with known metastatic adenocarcinoma.

Surgical resection of some early-stage tumors may be contraindicated because of concerns regarding reduced postoperative pulmonary function, ventilation or poor preoperative functional status. Up to 10 percent of patients successfully resected with lung cancer subsequently develop a second primary lung neoplasm.2

Using varying doses of low-intensity laser irradiation, cell growth functions can be stimulated or inhibited.4 One such treatment strategy used on cancer cells PDT, in which cancer cells are treated with a photosensitizer (PS) in combination with laser irradiation. Individually, they are non-toxic. However, with light-activation, reactive oxygen species are generated inducing cancer cell death.4 Cell-specific photosensitizers are in development for future cancer treatment.

Figure 4

Figure 3B: the mass following Photfrin© and first laser light treatment. The mass appears mucoid and less vascular.

After a photosensitizer is administered and the tumor is visualized, the light fiber is introduced through the working channel of the bronchoscope, and the rigid cylindrical tip of the light fiber is embedded into the lesion. This not only protects healthy mucosa from light exposure, but also delivers more energy to the tumor itself.

When the laser light is applied to the target area at the appropriate wavelength, the photosensitizer is activated, causing ROS generation that results in cancer cell death.5 A repeat bronchoscopy is planned 48 hours after the laser light exposure, when the inflammatory response is decreasing and tumor necrosis is achieved. At that time, all debris should be removed bronchoscopically.6

Figure 5

Figure 3C: the mass following the second light exposure and completion of debridement. Note that the right mainstem is patent and there is minimal scarring noted in the airway.

If a second operation may not be feasible for a patient, PDT can provide a therapeutic alternative that spares functional lung tissue required in lung cancer patients.3 Indications for PDT include treatment of micro-invasive endobronchial NSCLC in patients for whom surgery and radiotherapy are not indicated.3 Additionally, PDT can also be used to palliate symptoms in patients with completely or partially obstructing endobronchial masses due to non-small cell lung cancers.3

Figures 3A, 3B and 3C demonstrate a patient with a large right main-stem lesion recurrent NSCLC. In Figure 3A, the obstructing mass is noted in the right main-stem bronchus. Following the initial laser light therapy, the obstructing tumor was noted to have a more mucoid appearance allowing for initiating of debridement (Figure 3B). Serial light exposure and mechanical debridement allowed for local debridement of the complete obstructing mass (Figure 3C).

Interventional pulmonology is a rapidly burgeoning field providing novel and innovating, less-invasive ways of diagnosing and treating a variety of lung diseases. These are just a few of the novel diagnostic and therapeutic procedures available within the field of interventional pulmonology.


References

1. Spira A, Ettinger DS. Multidisciplinary management of lung cancer. N Engl J Med 2004; 350: 379–392

2. Chiaki E, Akira M, Akira S., et al. Results of Long-term Follow-up of Photodynamic Therapy for Roentgenographically Occult Bronchogenic Squamous Cell Carcinoma. Chest 2009; 136(2):369–375)

3. Moghissi K and K Dixon. Update on the current indications, practice and results of photodynamic therapy (PDT) in early central lung cancer (ECLC). Photodiagnosis Photodyn Ther. 2008 Mar;5(1):10-8

4. Crous, A., and H. Abrahamse: Lung cancer stem cells and low-intensity laser irradiation: a potential future therapy? Stem Cell Res Ther. 2013; 4(5):129.

5. El-Hussein A, Harith H, Abrahamse H. Assessment of DNA damage after photodynamic therapy using a metallophthalocyanine photosensitizer. International Journal of Photoenergy. 2012; 2012:1–10).

6. Edell ES, Cortese DA: Photodynamic therapy. Its use in the management of bronchogenic carcinoma. Clin Chest Med. 1995; 16(3):455).

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Georgia Neurosurgical Society Annual Fall Meeting

Friday, December 1st, 2017

December 1-3. The Ritz Carlton Reynolds , Lake Oconee, Greensboro, GA. For more information, visit the Georgia Neurosurgical Society.

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Georgia Emergency Medicine Leadership & Advocacy Conference

Thursday, November 30th, 2017

November 30 – December 1. The Ritz Carlton Reynolds , Lake Oconee, Greensboro, GA. For more information, visit Georgia College of Emergency Physicians.

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VillageMD and Quality Care Providers Team up to Form VillageMD-Georgia

Wednesday, October 4th, 2017

VillageMD, a national primary care provider, in collaboration with Quality Care Providers, Inc. (QCPI), an independent primary care physician network in Georgia, has formed VillageMD-Georgia. This new organization will support providers across Georgia.

QCPI, located in metropolitan Atlanta, Georgia, was founded in 1993. With over 1500 physician members, it is the largest independent network of primary care physicians in Georgia.

VillageMD-Georgia continues VillageMD’s expansion into the Southeast, and contributes to the growth of the VillageMD network of primary care physicians throughout the country. VillageMD partners with over 2,000 primary care providers across six states.

Michael J. Kinstler, MD

Michael J. Kinstler, MD

“Our relationship with VillageMD marks a critical next step in helping our physician members enrich and expand their high-quality services to support the total patient across the continuum of care leading to better outcomes and lower costs,” said Michael J. Kinstler, MD, President and Chief Medical Officer, QCPI. “VillageMD’s mix of technology, enhanced contracts and an advanced business model will also enable physicians to succeed under value-based care, and for the first time, access rewards for providing great patient care.”

VillageMD-Georgia will leverage VillageMD’s data analytics, physician-based care coordination, and on-the-ground support resources. VillageMD’s clinical care model also aids its physician partners in providing personalized attention, education, and support to patients via integrated care teams of health coaches, diabetes educators, pharmacists, and resource coordinators to address patients’ medical, emotional and social needs.

“We joined forces with QCPI because we share a common mission—to lead physicians into an era of primary care delivery that is more proactive, highly coordinated and complete,” said Tim Barry, chief executive officer, VillageMD.

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Georgia Academy of Family Physicians – Annual Scientific Assembly

Wednesday, October 25th, 2017

October 25-28. Westin, Buckhead, Atlanta. For more information, visit Georgia Academy of Family Physicians.

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MAA – MAG Foundation Distracted Driving Forum

Saturday, December 2nd, 2017

December 2. Woodruff Health Sciences Center Administration Auditorium, Atlanta. For more information, visit Medical Association of Atlanta

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Medical Association of Georgia House of Delegates

Saturday, October 21st, 2017

October 21-22. Hyatt Regency, Savannah. For more information, visit Medical Association of Atlanta

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MAA House of Delegates Caucus Meeting

Wednesday, October 11th, 2017

October 11. Piedmont Hospital – Rich Auditorium, Atlanta. For more information, visit Medical Association of Atlanta.

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Immunizations

Monday, October 2nd, 2017

By Helen K. Kelley

While some diseases are becoming rare due to vaccinations, it’s important to acknowledge that they haven’t been completely eradicated. The viruses and bacteria that cause measles, mumps, chicken pox, flu, HPV and other illnesses still exist – and can easily be spread by people who have not been immunized.

We recently spoke with two Atlanta-area physicians who discussed the importance of immunizations for children and adults, improvements in vaccines and the challenges physicians face in ensuring that their patients know and understand the significance of receiving appropriate immunizations.

Advocacy for Pediatric Immunizations

Dr. Sam Gold

Dr. Sam Gold

Sam Gold, M.D., chair for pediatrics for WellStar Medical Group, began his career when new vaccines were just coming on the market for many common childhood diseases.

“I remember taking care of children who were in the intensive care unit for pneumococcal meningitis. We saw that scenario often, along with chicken pox and other diseases,” he says. “Seeing the big changes that were brought about by vaccines was exciting to me, and I became an advocate for children’s immunizations.”

Citing a resistance toward immunizations by many parents in the last 15-20 years, Gold says that he and his colleagues on WellStar’s pediatrics leadership team saw the need for improved communication, education and advocacy. This led to the creation of policies that standardize how WellStar pediatricians address the subject of immunizations with parents and deliver them to patients.

“In the past, each office determined how it handled the issue. Some offices allowed for parents who didn’t want to immunize their children, but that created problems with scheduling,” Gold says. “Choosing not to immunize creates risks not only for those kids, but also for others, especially infants who haven’t yet been vaccinated and children with nonfunctioning immune systems. Additionally, some parents would say they wanted to exclude only one particular vaccine.

“But our physicians have found that all childhood vaccines are important,” he adds. “Therefore, we require our patients to have all of the immunizations recommended by the Georgia Department of Health. Also, we have standardized, across the WellStar system, the manufacturers that supply our vaccines. This has helped reduce the potential for errors in efficacy of the vaccines.”

Gold adds that educating the public about immunizations is an important, albeit challenging, part of the advocacy puzzle.

“It is extremely difficult to get the true message out. With the rise of social media, there are many people who, even though they are not experts, can make claims to a large audience. It’s a pushback to science and hard to refute with expert proof,” he says. “We’re seeing a lack of understanding among parents because global health has improved so dramatically in the 20th century due to immunizations. Because they were immunized as children, parents today didn’t experiences measles and mumps and aren’t familiar with those diseases. It’s a double-edged sword. The vaccines have been so effective that they’ve made the reasons for having them seem so remote.”

Immunizations Important for Adults, Too

Dr. Sandra Fryhofer

Dr. Sandra Fryhofer

Sandra Fryhofer, M.D., agrees that education is the key to getting adult patients on board with the immunizations they need to stay healthy.

“Every year, thousands of adult Americans die of diseases that could have been prevented by vaccines. But some people are resistant to getting immunizations, often because they lack information,” she says. “That’s why a recommendation from a physician can go a long way toward helping patients understand why vaccination is important.”

Fryhofer, an internal medicine practitioner, says she includes a discussion of vaccines as a regular part of each patient’s annual physical exam.

“I might mention a particular vaccine and then let the patient read the vaccination statement about why they need it and what the possible risks are, so they can make an informed decision,” she says.

In addition to discussing standard vaccines such as flu, hepatitis B, HPV and pneumococcal pneumonia, Fryhofer counsels patients who are planning international travel about the immunizations they’ll need.

“I routinely ask patients about their travel plans, because talking to a doctor about their trip probably isn’t on their radar,” she says. “Because we live in a developed country with clean water and food, most people haven’t considered the medical dangers of traveling abroad where resources are not as reliable. They also haven’t considered the possibility of bringing some diseases, like measles, back into the U.S., where they can be transmitted to other people.”

Fryhofer encourages those who are planning to travel out of the country to make sure they are up-to-date on basic immunizations like tetanus, Tdap and MMR and to be prepared if they are going to countries where they will need to be immunized against diseases like cholera and yellow fever.

“It’s important to know what you need well in advance. For example, right now there is actually a shortage of YF-VAX, the vaccine for yellow fever, due to a delay in the manufacturing process,” she says. “The good news is, the FDA is allowing the importation of Stamaril, a yellow fever vaccine made in Europe. It’s available only at a limited number of locations, though, so people will have to consult the travel page on the CDC’s website to find those clinics. The best advice physicians can give their patients who are planning to travel abroad is to be informed and not wait until the last minute to get what they need.”

Fryhofer adds that doctors can help their patients and their peers by entering vaccine information into the Georgia Registry of Immunization Transactions and Services (GRITS) database.

“Keeping track of immunization information can be a challenge. When a physician administers a vaccine and enters the information into GRITS, other physicians and public health officials can access it,” she says. “It’s a helpful tool, ensuring that patients are up to date on the immunizations they need to stay healthy.”

New Microneedle Patch for Flu Vaccination

flu microneedle

Applying a dissolving microneedle patch. The microneedles dissolve within minutes after insertion into skin to release encapsulated drug or vaccine. Georgia Tech.

A National Institutes of Health-funded study led by a team from the Georgia Institute of Technology and Emory University has shown that an influenza vaccine can produce robust immune responses and be administered safely with an experimental patch of dissolving microneedles. The method is an alternative to needle-and-syringe immunization; with further development, it could eliminate the discomfort of an injection as well as the inconvenience and expense of visiting a flu clinic.

“This bandage-strip sized patch of painless and dissolvable needles can transform how we get vaccinated,” says Roderic I. Pettigrew, Ph.D., M.D., director of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), which funded the study. “A particularly attractive feature is that this vaccination patch could be delivered in the mail and self-administered. In addition, this technology holds promise for delivering other vaccines in the future.”

The vaccine patch consists of 100 solid, water-soluble needles that are just long enough to penetrate the skin. Adhesive helps the patch grip the skin during the administration of the vaccine, which is encapsulated in the needles and is released as the needle tips dissolve, within minutes. The patch is peeled away and discarded like a used bandage strip.

The researchers enrolled 100 adult participants, dividing them into four random groups: vaccination with microneedle patch given by a healthcare provider; vaccination with microneedle patch self-administered by the study participant; vaccination with intramuscular injection given by a healthcare provider; and placebo microneedle patch given by a healthcare provider. The researchers used an inactivated influenza vaccine formulated for the 2014-15 flu season to inoculate participants other than those in the placebo group.

The researchers found that vaccination with the microneedle patches was safe, with no serious related adverse events reported. Some participants developed local skin reactions to the patches, described as faint redness and mild itching that lasted two to three days.

The results also showed that antibody responses generated by the vaccine, as measured through analysis of blood samples, were similar in the groups vaccinated using patches and those receiving intramuscular injection, and these immune responses were still present after six months. More than 70 percent of patch recipients reported they would prefer patch vaccination over injection or intranasal vaccination for future vaccinations.

The prospective vaccine technology could offer economic and manufacturing advantages. The manufacturing cost for the patch is expected to be competitive with prefilled syringe costs. The patch, however, can dramatically reduce the cost of vaccination, since self-administration can eliminate the need to have health workers oversee the process. It can be easily packaged for transportation, requires no refrigeration and is stable.

The team plans to conduct further clinical trials to pursue the technology’s ultimate availability to patients. They also are working to develop microneedle patches for use with other vaccines, including measles, rubella and polio.

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