ZSX 2nd Quarter 2010 Newsletter

Hello again and happy summer from ZSX Medical! This newsletter exists to serve those who want to keep up to date with what we're doing as a company. In this newsletter, we will briefly outline a few key developments in the company over the past three months, and discuss a topic of clinical interest. In this issue, the clinical topic is healing of the uterus after cesarean delivery.

Recent News
The big news is that we have completed our proof-of-concept studies! For many months, we have been testing and refining prototypes, making a product that would meet the needs of obstetricians. In our design and testing, we have accomplished each of the following:

1.    We made a series of clips that can close a uterine incision.
2.    We made our absorbable patch able to stick to the wall of the uterus.
3.    We reduced post-operative adhesions in both severity and extent using our absorbable patch in a pre-clinical model.

These studies, together, demonstrate proof-of-concept for Zip-Stitch™.
We are now moving forward into our second stage of development. This stage will require our formal introduction to the FDA as we continue through large animal trials, human trials, FDA market clearance, and ultimately, commercial success. Animal trials are costly, but will represent a huge jump in the value of ZSX. If we demonstrate safety and efficacy at this stage, our path to market becomes very bright.

As described in our previous newsletter, we presented at the most recent Angel Venture Fair in April of this year. Since that time, we have progressed into advanced investment discussions and due diligence with government agencies, individual investors, and angel investment groups. Interested, accredited investors are welcome to contact us for more information.

Uterine Healing after Cesarean Delivery
Cesarean delivery is, without a doubt, the greatest advance in the history of obstetrics. Cesarean delivery has saved the lives of many millions of mothers and babies. In the modern developed world, cesarean delivery has become so commonplace that we can forget that it is a serious, life-preserving surgery. When we hear of people talk of cesarean delivery as if it were no big deal, it is merely a testament to the high standard of care in cesarean delivery.

Nonetheless, cesarean delivery is major surgery, which causes significant internal damage and entails a long and difficult recovery period. We can observe the superficial incision as it heals, but even more important is the hidden scar on the uterus. How well does that scar heal?
It's hard to know right away how well the uterus is healing. Doctors have known for a long time that the tissue right next to a sutured incision becomes weakened.(1) But the uterus shrinks from the size of a basketball to the size of a fist in the first six weeks after delivery, and it isn't physically challenged again until it has to carry another baby. We could look at the uterus with ultrasound, and measure the scar, but there usually isn't sufficient reason to do that. So it may not be until a later pregnancy and delivery that we find out how well the uterus has healed.

What if Healing is not Complete? 
If the uterus isn't fully healed, it will be weaker than it was prior to cesarean delivery. When the uterus is "challenged" during labor, it will be more likely to tear near the location of the scar. This is called a dehiscence or a rupture, depending on how severe the tear is. Uterine dehiscence/rupture is almost three times as likely for women attempting a trial of labor after cesarean than for the laboring population as a whole,(2-4) so we know that the uterus after cesarean is often weaker than before cesarean.

Dehiscence is a rare complication, occurring in less than 2% of women undergoing a trial of labor after cesarean delivery. Nonetheless, it is serious enough that it affects standard of care. For example, if a woman who has never had a cesarean delivery carries a pregnancy for too long, doctors will give a medicine to cause her to go into labor. If the woman has had a prior cesarean, on the other hand, doctors will not give the medicine, but instead will do a cesarean delivery because the risk of rupture is too great.

VBAC_CS_Stats
Incidence of VBAC and CS from 1990-2010

Dehiscence is not the only problem with incomplete uterine healing. Other rare birth complications, such as placenta previa and placenta abruptio, are elevated in the post-cesarean sub-population. Furthermore, there are increasing reports of "Cesarean scar ectopic pregnancy," which is a complication early in pregnancy that is fatal for the baby, and dangerous for the mother if not identified and treated early.(5,6)

All this evidence of incomplete healing after cesarean delivery has led to a steep decline in vaginal birth after cesarean delivery (VBAC) in the past 15 years. In 1995, VBAC represented 28% of births after cesarean delivery in the U.S., but that number had dropped below 10% as of 2006.(7)

What Can We Do About It?
These rare but serious side effects could lead one to think we should abandon cesarean delivery altogether. This is not an option. As stated above, cesarean delivery is, in many cases, a life-saving procedure. But as a company developing surgical products, we don't have to be satisfied with the current standard-of-care, either. Sutures have been used to close the uterine incision for well over one hundred years. There have been various improvements in techniques and materials over time, but the fundamentals of closure by sutures have not changed: sutures close an incision by piercing through tissue and applying very high local stresses.

Our desire at ZSX Medical is to bring real improvement to the way the uterus heals. We are exploring a totally new way to hold closed the uterine wound: a method that does not pierce tissue, a method that does not apply high local stresses. This new method of closure opens the possibility of a real change in the way the uterus heals after cesarean delivery.

Cesarean Delivery in the News
For more popular press discussing the difficulties associated with cesarean delivery, see the recent Philadelphia Inquirer article, "Dangerous delivery shows peril of multiple C-sections," by Dr. Alex Friedman. Dr. Freidman closes his article with this strong warning, "With a first cesarean, the up-front costs - a few more days in the hospital, a longer recovery - may seem reasonable. Only in retrospect can the true costs become apparent."

Also, the Cortlandt Forum, an online journal for the medical community, recently published this article that talks about some of the lesser-known post-operative complications of cesarean delivery.

Keeping in Touch
ZSX Medical is reachable through www.zsxmedical.com or www.ZipStitch.com. In addition to this newsletter, we may use our site periodically as a mechanism to keep interested parties informed as to our progress. Check back often!
Dan Mazzucco, President & CTO
Eric Rugart, COO

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Bibliography

  1. Hastings JC, Winkle WV, Barker E, Hines D, Nichols W. Effect of suture materials on healing wounds of the stomach and colon. Surgery, gynecology & obstetrics. 1975;140(5):701-707. 
  2. Rossi AC, D'Addario V. Maternal morbidity following a trial of labor after cesarean section vs elective repeat cesarean delivery: a systematic review with metaanalysis. American journal of obstetrics and gynecology. 2008;199(3):224-231. 
  3. Akasheh F. Rupture of the uterus. Analysis of 104 cases of rupture. American journal of obstetrics and gynecology. 1968;101(3):406-408 
  4. Van der Merwe JV, Ombelet WU. Rupture of the uterus: a changing picture. Archives of gynecology. 1987;240(3):159-171
  5. Rotas MA, Haberman S, Levgur M. Cesarean scar ectopic pregnancies: etiology, diagnosis, and management. Obstetrics and gynecology. 2006;107(6):1373-1381. 
  6. Fylstra DL. Ectopic pregnancy within a cesarean scar: a review. Obstetrical & gynecological survey. 2002;57(8):537-543.
  7. HCUPnet, Healthcare Cost and Utilization Project. Agency for Healthcare Research and Quality. Available at: http://hcupnet.ahrq.gov/. Accessed March 11, 2010.

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