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1rem

Authors

Myre is a medical oncologist with Elmhurst Hematology Oncology Group in Elmhurst, Illinois.

"We feel a more appropriate approach would be to retain true Gleason 6 as a cancer of extremely low metastatic potential requiring close follow-up," write Harris et al.

Letter: Declassifying Gleason 6 as a cancer would do more harm than good

The FDA has accepted a Biologics License Application (BLA) seeking approval of nivolumab (Opdivo) co-formulated with Halozyme’s proprietary recombinant human hyaluronidase (rHuPH20), or subcutaneous nivolumab, for the treatment of patients with all previously approved solid tumor indications for nivolumab as a monotherapy, monotherapy maintenance following completion of combination therapy with nivolumab plus ipilimumab (Yervoy), or in combination with chemotherapy or cabozantinib (Cabometyx).

Nivolumab is currently approved under several indications, including in combination with ipilimumab for the first-line treatment of patients with intermediate- or poor-risk advanced renal cell carcinoma (RCC), in combination with cabozantinib for the first-line treatment of patients with advanced RCC, for the treatment of patients with advanced RCC who have received prior anti-angiogenic therapy, and in combination with cisplatin and gemcitabine for the first-line treatment of patients with unresectable or metastatic urothelial carcinoma.

The FDA is set to have a decision regarding the subcutaneous nivolumab formulation on or by December 29, 2024.

 According to a news release from Bristol Myers Squibb,

 approval of the formulation would make it the first and only subcutaneously administered PD-1 inhibitor.

“We believe subcutaneous nivolumab has the potential to make a significant difference in the lives of patients, which is reinforced by the FDA’s acceptance of our application,” said Gina Fusaro, PhD, vice president, global program lead, Bristol Myers Squibb, in the news release.

 “Opdivo is a foundational PD-1 inhibitor approved for many different types of cancer, and our continued investment in research that puts patients first remains a priority. If approved by the FDA, the subcutaneous administration of nivolumab would provide patients and their physicians with a new option that delivers the same well-known benefits as IV Opdivo but with the improved convenience of an injection administered in 3 to 5 minutes rather than a 30-to-60-minute infusion.”

The BLA submission is supported by findings from the phase 3 CheckMate-67T trial (NCT04810078), in which subcutaneous nivolumab met the study’s co-primary end points by demonstrating noninferiority to intravenous (IV) nivolumab regarding time average nivolumab serum concentration over 28 days (C

; geometric mean ratio [GMR}, 2.098; 90% CI, 2.001-2.200) and minimum serum concentration at a steady state (C

Data from the study, which were presented at the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium in San Francisco, California,

 also showed that subcutaneous nivolumab demonstrated noninferiority to IV nivolumab in the key powered secondary end point of objective response rate (ORR). Specifically, the subcutaneous arm demonstrated an ORR of 24.2% (95% CI, 19.0-30.0) per blinded independent central review (BICR), compared with 18.2% (95% CI, 13.6-23.6) in the IV arm.

The safety profile for subcutaneous nivolumab was consistent with that of the IV formulation. Among patients who received the subcutaneous formulation, 8.1% experienced injection-site reactions, with all being low-grade and transient. Deaths due to study drug toxicity occurred in 3 patients in the subcutaneous arm and 1 patient in the IV arm. Most deaths that occurred during the study were due to disease progression.

In total, the phase 3, open-label CheckMate-67T trial enrolled 495 patients with advanced or metastatic ccRCC who had received prior systemic therapy. Patients were randomly assigned 1:1 to receive 1200 mg subcutaneous nivolumab plus rHuPH20 every 4 weeks (n = 248) or to 3 mg/kg IV nivolumab every 2 weeks (n = 247) for up to 2 years of treatment or until disease progression, unacceptable toxicity, withdrawal, or death.

The co-primary pharmacokinetic end points for noninferiority testing were C

 of subcutaneous nivolumab vs IV nivolumab. The key secondary end point was ORR per BICR.

Final completion of the CheckMate-67T study is expected in January 2026.

1. U.S. Food and Drug Administration accepts Bristol Myers Squibb’s application for subcutaneous nivolumab (nivolumab and hyaluronidase). News release. Bristol Myers Squibb. May 6, 2024. Accessed May 7, 2024. https://news.bms.com/news/corporate-financial/2024/U.S.-Food-and-Drug-Administration-Accepts-Bristol-Myers-Squibbs-Application-for-Subcutaneous-Nivolumab-nivolumab-and-hyaluronidase/default.aspx

2. Bristol Myers Squibb announces updated action date by the U.S. Food and Drug Administration for subcutaneous nivolumab (nivolumab and hyaluronidase). News release. Published online and accessed May 21, 2024. https://investors.bms.com/iframes/press-releases/press-release-details/2024/Bristol-Myers-Squibb-Announces-Updated-Action-Date-by-the-U.S.-Food-and-Drug-Administration-for-Subcutaneous-Nivolumab-nivolumab-and-hyaluronidase/default.aspx

3. George S, Bourlon TB, Chacon MR, et al. Subcutaneous nivolumab (NIVO SC) vs intravenous nivolumab (NIVO IV) in patients with previously treated advanced or metastatic clear cell renal cell carcinoma (ccRCC): Pharmacokinetics (PK), efficacy, and safety results from CheckMate 67T. 

4. A study of subcutaneous nivolumab versus intravenous nivolumab in participants with previously treated clear cell renal cell carcinoma that is advanced or has spread (CheckMate-67T). ClinicalTrials.gov. Last updated March 1, 2024. Accessed May 7, 2024. https://clinicaltrials.gov/study/NCT04810078

The FDA is set to have a decision regarding the subcutaneous nivolumab formulation on or by December 29, 2024. 

News

FDA accepts BLA for subcutaneous nivolumab in solid tumors

Vikram M. Narayan, MD, discusses an ongoing study to evaluate the use of augmented reality to simulate surgical procedures for resident training.

Vikram Narayan, MD, on the use of augmented reality to assist in resident training

, discusses an ongoing study to evaluate the use of augmented reality to simulate surgical procedures for resident training. Narayan is an assistant professor of urology at Emory University and the director of urological oncology at Grady Memorial Hospital in Atlanta, Georgia. 

One of the roles that I have here at Emory is to help train the next generation of surgeons. I think the importance is how best to get those surgeons ready for their own independent practice. Historically, in surgical education, simulation has been a big area of interest and focus. I don't think we, to date, have a surgical simulator that matches the fidelity or realism of being at a patient's bedside.

One of the things that we are exploring here at Emory is the use of augmented and mixed reality and potentially virtual reality to try and help educate some of our resident surgeons. We have a recently approved, IRB approved study that I'm doing together with my colleague in the department of radiology, Dr. Elias Kikano, to use Apple Vision Pro to essentially do 3D simulation with imaging as well as review of surgical videos in an immersive space so as to try and improve the pre-operative and post-operative experience that a resident has, essentially trying to think through the best way to help augment their education. Put another way, with Apple Vision Pro, what we're hoping to do is have our residents be able to put on a headset and walk through a case before they actually walk into an operating room.

This is very important because right now, the way we do that is through didactic teachings. We'll have videos that are on a 2-dimensional screen, that don't necessarily capture the depth of being at a patient's bedside. We're hoping that with these sorts of tools, we'll be able to improve the comfort and readiness that a resident has by the time they show up in the operating room to assist in a case. It's very early days, but some of the things that we're doing are, with our residents, sitting them down, having them be in headset, in a vision Pro headset—which is a very new technology; it was only released earlier this year in February. So, we're very excited to have this IRB approved study to look at ways in which an attending physician can walk a resident through a case in headset and then figure out the next steps in terms of performance evaluation, that sort of thing.

This transcript was AI generated and edited by human editors for clarity.

Pictured in the video: Vikram M. Narayan, MD, Assistant Professor of Urology, and Donald Fedrigon, MD, PGY-5, reviewing 3D robotic surgery footage in Apple Vision Pro as part of a pre-procedure planning and didactics. October 29, 2024.

Augmented reality is being explored for surgical training at Emory University, led by Dr. Vikram M. Narayan. The study, in collaboration with Dr. Elias Kikano, utilizes Apple Vision Pro to create 3D simulations and immersive surgical video reviews. This approach aims to enhance the pre-operative and post-operative educational experiences of resident surgeons, moving beyond traditional didactic methods. The goal is to improve residents' comfort and readiness for real surgeries. The study is in its early stages, focusing on performance evaluation and educational augmentation.

“Put another way, with Apple Vision Pro, what we're hoping to do is have our residents be able to put on a headset and walk through a case before they actually walk into an operating room,” says Vikram M. Narayan, MD. 

The combination of tissue-based next-generation sequencing (NGS) with circulating tumor DNA (ctDNA) profiling increased the detection of genomic alterations in patients with renal cell carcinoma (RCC), according to data from a retrospective study presented at the 2024 Kidney Cancer Research Summit in Boston, Massachusetts.

The data were presented by Chinmay Jani, MD, a clinical fellow at the University of Miami Sylvester Comprehensive Cancer Center.

He explained, “Next generation sequencing of ctDNA can complement tissue NGS. The most important thing is it's a non-invasive test that can be conducted serially. Its application enhances the assessment of spatial as well as temporal molecular tumor heterogeneity, providing insights not into just progression, but also treatment response prognosis. However, limited studies have been conducted in RCC. The aim of our study was to investigate molecular alterations detected in circulating and tissue-derived DNA in patients with RCC.”

Overall, data from the study showed that NGS with both tissue and ctDNA sampling increased the detection of genomic alterations among patients with RCC. There was a higher concordance of somatic alterations between the 2 in patients with metastases vs those without, particularly between select genes such as 

 (55.9% vs. 9.1% for metastases vs non-metastases, respectively), 

 (25% vs. 0%). According to the authors, this finding suggests “the potential utility of ctDNA analysis in advanced stages of RCC.”

Among the tissue samples, the prevalence of pathogenic somatic short variants was 59% (n = 232) in 

. In ctDNA samples, the prevalence of molecular alterations was 23% (n = 91) in 

In total, the retrospective study included de-identified NGS data from 393 patients, collected from the Tempus multimodal database. All patients included for analysis had matched samples, meaning their tissue and ctDNA testing were conducted within 90 days of each other. The median time from tissue to blood collection 21 days (IQR, 7-39). The most common tissue biopsy sites were kidney (49%, n=189), bone (11%, n=43), lung (9%, n=34), lymph node (8%, n=29), liver (6%, n=23), and brain/CNS (4%, n=17).

The median age of patients in the study was 61 years, and 71% were male. Among all patients, 75% were white, 12% were African American, 4.8% were Asian, and 8% were of another race.

Overall, Jani concluded in the presentation, “Further research is warranted to illustrate how longitudinal ctDNA analysis can delineate biomarkers of response and resistance at both the mutation as well as at the ctDNA fraction levels. Understanding these dynamics will not only offer valuable insights, [but] it will [also] help us understand how to utilize this testing in disease progression and treatment outcomes and give personalized treatment to all patients with RCC.”

1. Jani C, Tran E, Hockenberry A, et al. Concordance analysis of tissue and circulating tumor DNA (ctDNA) in renal cell carcinoma (RCC): Insights from a multimodal real-world database. Presented at: 2024 Kidney Cancer Research Summit. July 11-12, 2024. Boston, Massachusetts. Abstract 12. Accessed July 17, 2024. https://kcrs.kidneycan.org/wp-content/uploads/2024/06/KCRS24-Abstract-Book-6.27.24.pdf

Combining tissue-based next-generation sequencing (NGS) with circulating tumor DNA (ctDNA) profiling enhances the detection of genomic alterations in renal cell carcinoma (RCC). This retrospective study, presented at the 2024 Kidney Cancer Research Summit, highlights the increased concordance of somatic alterations in metastatic patients, particularly in genes like BAP1, TP53, and VHL. The study analyzed data from 393 patients, revealing significant differences in the prevalence of pathogenic variants between tissue and ctDNA samples. Further research is needed to explore ctDNA's role in understanding treatment response and disease progression in RCC.

here was a higher concordance of somatic alterations between tissue and ctDNA testing in patients with metastases vs those without.

ctDNA profiling complements tissue-based NGS in renal cell carcinoma

, highlights 2 sessions that she took part in during the 2024 

American Urological Association (AUA) Annual Meeting

 in San Antonio, Texas on urodynamics in the context of the VALUE trial (NCT00803959) and the new wave of percutaneous tibial nerve stimulation (PTNS) devices. Syan is an assistant professor of clinical urology at the University of Miami in Florida.

This transcription has been edited for clarity.

At this year’s AUA, you were a part of the session, “UDS and Female SUI in the Era of the VALUE Trial: Is it Needed? Debate and Panel Discussion of Cases with Audience Response.” Could you provide an overview of this discussion?

Urodynamics is a study to evaluate bladder function. It's minimally invasive, but it's still invasive; it requires a catheter in the bladder. It's not a painful procedure, but it's uncomfortable. It does require patients interacting with providers while they're urinating, so patients don't really look forward to the study. However, it provides excellent diagnostic understanding of bladder function during filling and emptying. So, it's a really valuable tool, but we don't want to overuse it either. The guidelines published by the AUA and SUFU [Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction] focused on the uncomplicated patient with stress urinary incontinence. Do they really need to undergo urodynamics prior to undergoing surgical therapy for stress urinary incontinence? That's what the VALUE trial was aiming to [understand]. They had pretty strict criteria to define an uncomplicated straightforward stress incontinence patient. They randomized to either undergo majority sling, some bulking vs urodynamics and then a sling. They show that urodynamics had no impact on patient outcomes, patient quality of life, or success of the operation. So, really in the uncomplicated patient, you don't need to perform urodynamics.

Now, the uncomplicated patient is the minority. The majority of patients have some degree of other bladder issues. It might be over activity, it might be under activity, there may be some component of obstruction. Even in the VALUE trial, only 33% of patients met criteria for being the uncomplicated patient. So, the debate really is, "Okay, so how far can we push the findings from VALUE trial? How much can we avoid an unnecessary procedure in our patient population?" And I argue the side that we should use diagnostics when there are hints of possible underlying other disorders, because this will help us with patient counseling and management of post-operative outcomes, if they elect for surgery, and other treatment options if they exist.

At the AUA, you also participated in the session, “Panel Discussion: Management of Refractory OAB - The New Crop of Implantable PTNS Device.” Could you provide an overview of this discussion?

Overactive bladder is a very common disorder that people experience, and unfortunately, it can be quite resistant to treatment. A lot of oral therapies exist out there, but they're limited in efficacy. Fortunately, we have amazing innovations in device developments that can really improve overactive bladder. One of them is the classic percutaneous tibial nerve stimulation. The way I describe it to patients is it's like a tiny little acupuncture needle; it doesn't cause any bleeding. We insert it right at the ankle where the tibial nerve is. The tibial nerve connects all the way back up at the spinal cord level to the big nerve, S3, that goes to the bladder. By coming to clinic once a week for 30 minutes for 12 weeks, patients just get a little electrical therapy session, [they can] bring a book and for 30 minutes get a little buzz sensation in their ankle. It's quite effective; it's 70%, effective at improving overactive bladder.

The big challenge is patients have to travel once a week. Visits to the clinic are really burdensome, and we're talking about 3 months of weekly visits. Also, as we know, in America, access to specialized care is really limited outside of our major cities. Fortunately, companies have developed the opportunity for implantable devices. There are 2 FDA approved devices, called the BlueWind Revi and the Valencia eCoin. [They are] very similar in that they involve the implantation of a small component. With BlueWind, you wear a little ankle sock that allows you to give therapy to yourself. When you're at home, you just turn it on. The eCoin, once it's implanted, you don't have to think about it. eCoin turns on and off on its own. Really, the advent of these new therapies is to improve access to care for patients and [provide] less burdensome care in terms of transportation and time off work. The debate is to decide which one is better. It's a blessing and a curse to be in a field that has so much innovation. It's a blessing because innovation is good for patients and for physicians and for everybody. Curse, because how do we decide which one? That's really what the debate was about, helping clinicians decide which one to pursue or which one is right for one patient vs another.

Building off that, how do you determine which device is better suited for each patient?

I think that's really the challenge, right? Some patients like the idea of having complete control. The BlueWind Revi allows for that. It's almost like a little tiny capsule that we place under the skin. You can barely feel it. The patient decides when they want to give themselves the therapy. They actually wear this little ankle brace, and they turn it on and off. They have complete control in that scenario.

Some other patients may not want to think about it at all. They want the little device to do the work for them. That would be the Valencia eCoin, which as I mentioned, it's just on and off on its own. The patient doesn't have control over it. It really comes down to what patients feel about the control or lack thereof that they want of their device. As someone who does do a lot of implantation, specifically sacral neuromodulation, I can tell you patients know what they want. They know whether they want to be aware or unaware. Again, it's really great to be able to provide patients the option.

Are there any emerging applications for these devices or additional potential in the field?

One of the innovations that I think the field needs to turn to is neuromodulation efficacy in neurogenic bladder. We really shied away from looking at neuromodulation in this population because previously, these devices were MRI incompatible, and patients with neurologic diseases often need MRI imaging. Other issues are when you lack sensation, you may not feel pain or infection. So, it's a really under explored area. With the implementation of these low-risk, minor procedures, placing it in the clinic, I think the opportunity to examine neuromodulation efficacy in various neurologic conditions—MS, stroke, Parkinson's disease, spinal cord injury, incomplete spinal cord injury—is really where we should turn our attention and explore.

Dr. Raveen Syan participated in sessions at the 2024 AUA Annual Meeting, discussing urodynamics in the context of the VALUE trial and advancements in PTNS devices. The VALUE trial indicated that urodynamics may not be necessary for uncomplicated stress urinary incontinence patients, though most patients present with additional bladder issues. Innovations in PTNS devices, such as BlueWind Revi and Valencia eCoin, offer improved access and convenience for managing refractory overactive bladder. The choice between devices depends on patient preference for control. Future exploration may focus on neuromodulation efficacy in neurogenic bladder conditions.

Raveen Syan, MD, highlights 2 sessions that she took part in during the 2024 AUA Annual Meeting in San Antonio, Texas on urodynamics in the context of the VALUE trial and the new wave of percutaneous tibial nerve stimulation devices.

Dr. Syan recaps AUA 2024 sessions on urodynamics, PTNS devices

Raveen Syan, MD, FPMRS, shares her thoughts on the 2024 Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction Winter Meeting

Dr. Syan shares her thoughts on SUFU 2024

 shares her thoughts on the 2024 Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction Winter Meeting. Syan is an assistant professor in clinical urology at the University of Miami Desai Sethi Urology Institute in Miami, Florida.

SUFU in 24 was another great meeting. The best thing about SUFU is always that you see the young trainees really start to build their skills as speakers and presenting their research. I was moderating the fellows forum, and [there is] really great research coming out of these different institutions. You really see rising stars. [It's] so wonderful to see young trainees getting engaged in the world of urogynecology and pelvic reconstruction. A lot of what they were focusing on were things like quality-of-life outcomes, or outcomes related to new innovations, such as new implantable tibial devices. That was really exciting. It's always good to see the emerging young doctors succeed and have interest. It was very interesting to hear about all these new implantable tibial devices and hear how well they're doing. What's interesting is they're all slightly nuanced, so I think as a provider, it will be a journey to figure out what I would recommend the most, what I think is best for the patient. But at the end of the day, it's nice to have a tailored approach and options available for the individual patient. Other things that stood out to me at the talk [included] the basic science component at SUFU. It starts off the course. It's always great for someone who's not a basic scientist like myself, to hear a really good summary, which is what was done on Friday morning. It was really interesting to hear that apparently umbrella cells are the new hot cell of the bladder, and I am excited to hear more about that, and how that may influence the physiology of the bladder and bladder symptoms. It was also a great hotel; they chose an excellent spot in beautiful Fort Lauderdale. And at the end of the meetings, a lot of us would meet at night, and it was just a great way to interact on an informal level and continue to build our networking and collaboration. It's a really important thing to create that interfacing; that's how new research [and] new ideas are formulated. One of the very interesting talks was the SOTA Lecture, where Dr. Andrew C. Peterson describes the end stage bladder, and it's always great to hear from experts and experienced clinicians about how they handle these very difficult cases. And I think that's one of the things SUFU does best, which is showcase these challenging, difficult-to-treat situations and really helps contextualize it. He did a great job of explaining how should we define the end stage bladder? Because that's a little vague. And then how do we talk to patients about it, and most importantly, what do patients have to say? And he shared a beautiful video by a patient who talked about how difficult that decision was to do some major surgery and how incredibly impactful in a positive way undergoing that surgery was. So it was great to hear, as a younger clinician, how others talk to patients, how patients do, how do we face these difficult challenges. SUFU is a fantastic organization where they're very much focused on partnership between all stages of your career: research, clinical care, outcomes. And SUFU really leads the nation in terms of defining urogynecologic problems and how we should treat [them] expertly with care and with attention to what's important to patients. It's a meeting I look forward to every year because I learn so much. I have the opportunity, I feel, to share what I am learning and every time I leave the meeting, I just feel reinvigorated, refreshed, and excited about this field that we're a part of.

This transcription was edited for clarity.

The 2024 Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction Winter Meeting highlighted the development of young trainees in urogynecology and pelvic reconstruction, focusing on quality-of-life outcomes and innovations like implantable tibial devices. The meeting emphasized the importance of networking and collaboration in advancing research and clinical practice. Key discussions included the role of umbrella cells in bladder physiology and the management of end-stage bladder conditions. The event underscored SUFU's commitment to integrating research, clinical care, and patient-centered approaches in urogynecology.

"Every time I leave the meeting, I just feel reinvigorated, refreshed, and excited about this field that we're a part of," says Raveen Syan, MD, FPMRS.

Max D. Sandler discusses findings on patient preference toward humor or professionalism in urologists

Study: Humor-centric approach to ED care may not resonate with all patients 

 highlights the background and key findings from the study, “Prospective Patient Preferences for Humor in Urologists Treating Erectile Dysfunction: A Survey Study,” for which he served as the lead author. Sandler is a third-year medical student at the University of Miami Miller School of Medicine in Miami, Florida.

Could you describe the background for this study?

First, just wanted to thank you for the opportunity to speak with you today. At least in my experience, urologists tend to be some of the funniest and most approachable physicians in the hospital. So, I thought it would be interesting to see how those traits made patients feel, especially for patients who might have a stigmatized condition like erectile dysfunction. So, unfortunately, there's not a lot of research on humor. It's hard to standardize; it's hard to study. So, I couldn't find that much literature out there, but I was able to find one study by an author named [Elisabeth] Sartoretti, and they found that women who received a funny business card during a routine mammogram screening tended to remember the radiologist's name better, they tended to rate the encounter as more positive overall. That's the background that helped guide me when I started thinking about how I wanted to do this project.

We created 5 pairs of mock business cards. They were for physicians; the business cards were physician business cards. In each pair, one was a humorous card, and one was a professional card. The funny card alluded to erections. For example, had a symbol of a diamond and the caption was "harder is better" on the business card, while the professional card just advertised expertise in health care, and didn't mention ED or anything. We posted an anonymous survey online to a website where respondents completed short tasks like surveys. Our survey basically asked them to imagine that they had erectile dysfunction and they're seeking a urologist to help them. Then they were asked which urologist they'd rather see based on the business cards of Dr. Smith or Dr. Jones, which were just the names that we assigned to the funny or the professional business card in each question. Respondents were able to pick Dr. Smith, Dr. Jones, I wouldn't care if I saw either urologist, or neither––they don't want to see either of them.

We had almost 1000 participants. The results showed a preference for the professional card in almost all questions. Across the whole survey, an average of 66% preferred the professional card. The highest rate of selection of the humorous card in a single question was only 38.4%. So, honestly, it was a bit of a surprise to us. We had a suspicion that participants would enjoy or appreciate a little bit of humor. We thought maybe it'd be more enjoyable for participants to seek out a physician who embraces humor, which would be similar to the results of the radiology study that I mentioned earlier. But something to keep in mind is that the participants in our study were prospective patients. So, they might not really have erectile dysfunction. They were completing tasks online, and they were being compensated, so efficiency might be a goal of theirs. We thought maybe they just might have seen this as a medical themed survey. So, they might have just chosen a professional card due to medicine's inherent ties to expertise. We think that the results of this study perhaps would be pretty different if it was conducted in a real clinic [with] real patients who actually have a stigmatized condition like erectile dysfunction, because they feel a stigma. People with a stigma may better appreciate humor to break the ice and create a trustworthy atmosphere with physicians.

“Across the whole survey, an average of 66% preferred the professional card. The highest rate of selection of the humorous card in a single question was only 38.4%,” says Max D. Sandler.  

Brian Myre, MD

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