After she had a miscarriage, psychologist Jessica Zucker wanted to help other women tackle the stigma.
Jessica Zucker, M.P.H., Ph.D., was 16 weeks pregnant with her second child when she had a miscarriage in 2012. Zucker, a Los Angeles-based psychologist specializing in women’s reproductive and maternal mental health, had spent almost a decade treating women after pregnancy loss. But it wasn’t until it happened to her that she truly understood the stigma and silence surrounding miscarriages. After her own pregnancy loss, she set about telling her own story through essays and using the hashtag #IHadAMiscarriage. In 2015, she started the @IHadAMiscarriage Instagram account, where women can submit their own stories of pregnancy loss.
Sadly, miscarriages are incredibly common. But women often feel alone when it actually happens to them.
According to the American Congress of Obstetricians and Gynecologists (ACOG), 10 percent of clinically recognized pregnancies end in miscarriage, and many more people will lose a pregnancy before they even knew they were expecting. Most miscarriages happen in the first trimester, and as ACOG notes, around 50 percent are caused by chromosomal abnormalities.
Zucker’s own traumatic miscarriage happened in her second trimester. “My first pregnancy was smooth and simple and fine,” she says. “All the while I was coming across women in my practice talking about miscarriage, stillbirth, infant loss…. It didn’t pique my anxiety, I felt like I would be fine. Several years later we decided to try again. We got pregnant again quickly but at 16 weeks, I started spotting.”
She went into labor and delivered alone at home, cut the umbilical cord herself, and began hemorrhaging. Her husband returned home and rushed her to the hospital, where she underwent an unmedicated dilation and curettage to remove the placenta and the remnants of the pregnancy.
“Two hours later I went back to my house and was no longer pregnant,” Zucker recalls. “That was pretty much the most profound thing that ever happened in my life. The most traumatic.”
Medical tests revealed the fetus had chromosomal abnormalities, and Zucker would likely have made the decision to terminate had she known this. She and her husband began trying again when they were ready, and she eventually gave birth to a rainbow baby. “I was [debilitated], psychologically, through my subsequent pregnancy,” Zucker says. “Pregnancy after loss…you’re basically returning to the very place of your trauma. You are meant to be there for nine months, every single day.”
Zucker’s own experience informed her clinical practice going forward. “My loss really scared a lot of my patients and comforted other people,” she says. “In the most profound way it changed my lens on my work. I was able to understand these women from the inside out now.”
Ever since her pregnancy loss, Zucker has worked to spread awareness about just how common miscarriages are and help women deal with their feelings of shame and helplessness.
“My personal experience was a way to model for other women around the world that there is absolutely no shame in loss,” she says. “The research overwhelmingly points to women experiencing shame, self-blame, and guilt following pregnancy and loss. I had to really think it through. As a psychologist, you don’t typically share the details of your life. But [pregnancy loss] doesn’t mean anything about who you are, or your body being a failure.”
Each year in October, Zucker commemorates National Pregnancy and Infant Loss Awareness Month with a project. One year she released a line of sympathy cards specifically designed for women who have lost a pregnancy; another she made T-shirts encouraging women to have intergenerational conversations with their mothers and grandmothers about miscarriages. Through her Instagram account and the #IHadAMiscarriage hashtag, Zucker hopes to show other women that they are absolutely not alone.
“By putting it out there in the world and sharing it with women globally, people then feel this sense of recognition and a robust community,” she says. “I don’t have to know you, because it’s social media, but I know those feelings so well. In so many of comments or messages people say, ‘I could have written this myself.’ Part of the point is to really show that we’re more similar than we think.”
Check out some of the stunning posts from @IHadAMiscarriage below.
View original post here – http://www.self.com/story/antidepressant-use-during-pregnancy
The success of transplantations with Human Leukocyte Antigen (HLA) mismatches depends on donor Natural Killer (NK) cell alloreactivity which plays an important role in mediating Graftversus Leukemia (GvL) effect without Graft versus Host Disease (GvHD) in recipients. However, there is still a debate on whether Killer Immunoglobulin Receptor (KIR) ligand incompatibility between donor and recipient might favor Natural Killer (NK) cell alloreactivity after Unrelated Cord Blood Transplantation (UCBT) in Acute Myeloid Leukemia (AML) patients, hence the rationale for this study.
Stéphanie Nguyen from AP-HP, Hôpital Pitié Salpêtrière (AP-HP), Service d’Hématologie Clinique, Paris, France and colleagues discuss results from their prospective phase II study, which assessed the impact of KIR-ligand incompatibilities and NK cell reconstitution on clinical outcomes in AML patients in Complete Remission who underwent UCBT after a Reduced Intensity Conditioning (RIC). This study was conducted by the Société Française de Greffe de Moelle Osseuse et Thérapie Cellulaire and Eurocord. The results of the study were published ahead of print in Bone Marrow Transplantation on 26th June 2017.
In total, seventy-nine de novo AML patients (median age = 50 years) in CR were enrolled in 23 French hospitals from October 2007– September 2009 for this phase II study. Peripheral blood samples and DNA samples were collected in recipients and cords blood and analyzed in fifty-four AML patients in CR who underwent RIC-UCBT. The inhibitory KIRs, KIR2DL1, and KIR2DL2/3 bind KIR HLA ligand C2 and C1 respectively, resulting in inhibition of NK-cell mediated lysis. Recipients and Unrelated Cord Blood (UCB) were classified into C1 or C2 family depending on their HLA-C typing (C1-C1, C1-C2 or C2-C2).
The key results of the study were:
- Treatment Related Mortality (TRM) was associated with a low frequency of CD16 (Fc receptor found on the surface of NK cells) on NK cells; HR = 0.97, P = 0.043
- TRM incidence was significantly associated with a high level of HLA-DR (NK cell activation marker); HR = 1.08, P = 0.0008
- Low CD107a (NK cell degranulation marker) was significantly associated with a worse OS; HR = 0.95, P = 0.001
- Median Overall Survival (OS) in homozygous HLA-C2/C2 and heterozygous HLA- C1/C2 (C1/x) recipients; 3.8 vs 29.9 months, HR = 6.12, P = 0.001
- Compared to C1/x recipients, C2/C2 recipients had a higher Relapse Free Survival (RFS [HR = 5.04, P = 0.024]) and TRM incidence (HR = 9.44, P = 0.026)
In summation, homozygous HLA C2/C2 recipients have a worse clinical outcome after RIC-UCBT. Moreover, low expression of CD16 and CD107a were associated with increased incidence of TRM and worse OS respectively thus indicating an “impairment in the NK licensing process in HLA-mismatched” transplantation.
Overall, the authors concluded that “HLA-dependent and independent NK-cell features may play complementary roles in clinical outcomes after RIC-UCBT”. Additionally, they suggested that “further exploration should help in the development of future strategies to select optimal UCB units and enhance immune recovery”.
Unrelated cord blood transplantation (UCBT) after a reduced intensity conditioning regimen (RIC) has extended the use of UCB in elderly patients and those with co-morbidities without an HLA-identical donor, although post-transplant relapse remains a concern in high-risk acute myeloid leukemia (AML) patients. HLA incompatibilities between donor and recipient might enhance the alloreactivity of natural killer (NK) cells after allogeneic hematopoietic stem-cell transplantation (HSCT). We studied the reconstitution of NK cells and KIR-L mismatch in 54 patients who underwent a RIC-UCBT for AML in CR in a prospective phase II clinical trial. After RIC-UCBT, NK cells displayed phenotypic features of both activation and immaturity. Restoration of their polyfunctional capacities depended on the timing of their acquisition of phenotypic markers of maturity. The incidence of treatment-related mortality (TRM) was correlated with low CD16 expression (P=0.043) and high HLA-DR expression (P=0.0008), whereas overall survival was associated with increased frequency of NK-cell degranulation (P=0.001). These features reflect a general impairment of the NK licensing process in HLA-mismatched HSCT and may aid the development of future strategies for selecting optimal UCB units and enhancing immune recovery.
Immune cells with a general knack for recognizing and killing many types of infected or abnormal cells also can be engineered to hunt down cells with specific targets on them to treat cancer, researchers at The University of Texas MD Anderson Cancer Center report in the journal Leukemia.
The team’s preclinical research shows that natural killer cells derived from donated umbilical cords can be modified to seek and destroy some types of leukemia and lymphoma. Genetic engineering also boosts their persistence and embeds a suicide gene that allows the modified cells to be shut down if they cause a severe inflammatory response.
A first-in-human phase I/II clinical trial of these cord-blood-derived, chimeric antigen receptor-equipped natural killer cells opened at MD Anderson in June for patients with relapsed or resistant chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), or non-Hodgkin lymphoma. All are cancers of the B cells, another white blood cell involved in immune response.
“Natural killer cells are the immune system’s most potent killers, but they are short-lived and cancers manage to evade a patient’s own NK cells to progress,” said Katy Rezvani, M.D., Ph.D., professor of Stem Cell Transplantation and Cellular Therapy.
“Our cord-blood derived NK cells, genetically equipped with a receptor that focuses them on B-cell malignancies and with interleukin-15 to help them persist longer — potentially for months instead of two or three weeks — are designed to address these challenges,” Rezvani said.
Moon Shots Program funds project
The clinical trial is funded by MD Anderson’s Moon Shots Program™, designed to more rapidly develop life-saving advances based on scientific discoveries.
The chimeric antigen receptor (CAR), so-called because it’s added to the cells, targets CD19, a surface protein found on B cells.
In cell lines and mouse models of lymphoma and CLL, CD19-targeted NK cells killed cancer cells and extended survival of animals compared to simply giving NK cells alone. Addition of IL-15 to the CD19 receptor was crucial for the longer persistence and enhanced activity of the NK cells against tumor cells.
NK cells are a different breed of killer from their more famous immune system cousins, the T cells. Both are white blood cells, but T cells are highly specialized hunters that look for invaders or abnormal cells that bear a specific antigen target, kill them and then remember the antigen target forever.
Natural killers have an array of inhibitory and activating receptors that work together to allow them to detect a wider variety of infected, stressed or abnormal cells.
“By adding the CD19 CAR, we’re also turning them into guided missiles,” said Elizabeth Shpall, M.D., professor of Stem Cell Transplantation and Cell Therapy.
Using a viral vector, the researchers transduce NK cells taken from cord blood with the CD19 CAR, the IL-15 gene, and an inducible caspase-9-based suicide gene.
Cell line tests found the engineered NK cells to be more efficient killers of lymphoma and CLL cells, compared to unmodified NK cells, indicating the engineered cells’ killing was not related to non-specific natural killer cell cytotoxicity.
Another experiment showed the engineered cord blood NK cells killed CLL cells much more efficiently than NK cells taken from CLL patients and engineered, highlighting the need to transplant CAR-engineered NK cells from healthy cord blood rather than use a patient’s own cells.
Suicide gene to counter cytokine release syndrome
Mouse model lymphoma experiments using a single infusion of low dose NK cells resulted in prolongation of survival. At a higher, double dose, none of the mice treated with the CD19/IL-15 NK cells died of lymphoma, with half surviving for 100 days and beyond. All mice treated with other types of NK cells died by day 41.
A proportion of mice treated with the higher dose of engineered NK cells died of cytokine release syndrome, a severe inflammatory response that also occurs in people treated with CAR T cells.
To counteract this toxicity, the researchers incorporated a suicide gene (iC9) that can be activated to kill the NK cells by treatment with a small-molecule dimerizer. This combination worked to swiftly reduce the engineered NK cells in the mouse model.
Subsequent safety experiments were conducted in preparation for the clinical trial. Rezvani, the principal investigator of the clinical trial, says the protocol calls for vigilance for signs of cytokine release syndrome, treatment with steroids and tocilizumab for low-grade CRS with AP1903 added to activate the suicide gene for grade 3 or 4 CRS.
NK CARs available off the shelf
T cells modified with chimeric antigen receptors against CD19 have shown efficacy in clinical trials. In these therapies, a patient’s own T cells are modified, expanded, and given back to the patient, a process that takes weeks. Finding a matched donor for T cells would be a challenge, but would be necessary because unmatched T cells could attack the recipient’s normal tissue – graft vs. host disease.
Rezvani and Shpall have given patients cord-blood derived NK cells in a variety of clinical trials and found that they do not cause graft vs. host disease, therefore don’t have to be matched. NK cells can be an off-the-shelf product, prepared in advance with the necessary receptor and given promptly to patients.
“CAR NK cells are scalable in a way that CAR T cells are not,” Rezvani noted.
A strength of T cells is the development of memory cells that persist and repeatedly attack cells bearing the specific antigen that return. NK cells do not seem to have a memory function, but Rezvani says the experience of the longer-lived mice, which are now more than a year old, raises the possibility that a prolonged NK cell attack will suffice.
Shpall, Rezvani and colleagues are developing cord blood NK CARs for other targets in a variety of blood cancers and solid tumors.
MD Anderson and the researchers have intellectual property related to the engineered NK cells, which is being managed in accordance with the institution’s conflict-of-interest rules.
Shpall founded and directs MD Anderson’s Cord Blood Bank, originally established to provide umbilical cord blood stem cells for patients who need them but cannot get a precise donor match. Donated by mothers who deliver babies at seven Houston hospitals and two others from California and Michigan, the bank now has 26,000 cords stored. MD Anderson researchers pioneered the extraction and expansion of NK cells from umbilical cords.
Period pain isn’t always normal – excruciating pain can be a sign of endometriosis. Now it seems that the severity of pain is a sign of how extensive the condition is, with very bad pain linked with fertility problems.
Although around 10 per cent of women have endometriosis, little is known about the condition. It involves uterus cells turning up elsewhere in the body, where they bleed every month, which appears to cause scar tissue and pain. These out-of-place cells are usually found on the ovaries or fallopian tubes, but they have also been found on the intestines and even on the lungs and the brain.
Over time, endometriosis might lead to fertility problems; around a third of women with the condition may be infertile. And while some people experience only a little pain, for others it can be much worse.
No one knows why the symptoms of endometriosis can vary so much between women, says Mathilde Bourdon at Descartes University, Paris. “Some women have little or no symptoms, while others have major impairments to their quality of life,” she says.
To find out if the severity of endometriosis pain might be linked to how many uterus cells have spread, where they have spread to, and the damage they have caused, Bourdon and her colleagues spoke to women who had been treated for the condition between 2004 and 2017.
The team identified 422 women who had been unable to conceive naturally after a year. When they were asked to score their endometriosis pain on a scale of 1-10, 289 of them rated it as a seven or higher.
By looking at surgical reports, Bourdon’s team found that those who reported worse pain had more extensive disease – the patches of endometriosis were deeper in the body, and more likely to be found on the intestines. Those who rated their pain as six or lower were less likely to have deep lesions and less likely to have endometriosis on their intestines.
Women who reported being in more pain also took significantly longer to get pregnant, and ended up needing more surgery and more fertility treatments before doing so. Bourdon presented her findings at the annual meeting of the European Society of Human Reproduction and Embryology in Geneva, Switzerland, this month.
Andrew Horne, at the University of Edinburgh, UK, hopes these findings will raise awareness of endometriosis among doctors. It currently takes between seven and 11 years for a woman with endometriosis to receive a diagnosis.
But the issue of pain in endometriosis is far from settled, says Horne. “We still don’t fully understand why women with endometriosis experience pain.”
Bourdan thinks it is vital that doctors pay close attention when a woman says she has pelvic pain. “Women with endometriosis require specific care, preferably in a specialist centre,” she says.
But women’s pelvic pain is often seen by doctors as a normal experience, says Federica Facchin at the Catholic University of Milan in Italy, who is studying the effects of endometriosis on mental health. This can be why it takes so long to get diagnosed with endometriosis, she says.
Horne advises women to seek specialist treatment for endometriosis. “If you’re not getting it, persevere,” he says.
Read more: New treatment for endometriosis preserves fertility
View original article here – https://www.newscientist.com/article/2140643-women-with-worse-endometriosis-pain-have-more-fertility-problems/
Women exposed to cigarette smoke while in their mothers’ wombs are more likely to experience miscarriage as adults, according to a study.
University of Aberdeen researchers found the link remained even after taking account of the smoking habits of the women themselves who miscarried.
But no link was found between exposure to cigarette smoke in the womb and a decrease in fertility.
The study examines data from 12,321 women born before 31 December 1972.
The university said an analysis of the data also showed that women exposed to cigarette smoke in the womb were more likely to have a pregnancy than those whose mothers did not smoke.
Women exposed to cigarette smoke in the womb were also likely to have a pregnancy earlier than those not exposed.
Dr Sohinee Bhattacharya, a pregnancy and childbirth expert from the University of Aberdeen, said previous research had suggested there may be a “small decrease” in the fertility of women whose mothers smoked in pregnancy.
“This study used a databank in Aberdeen to look at the birth records of more than 12,000 women and followed them through for 40 years to see whether being born to a smoker had any impact on women’s future fertility,” she said.
“The study did not find a link between mothers’ smoking and a decrease in fertility in their daughters.
“Women whose mothers smoked were more likely to have a pregnancy, but this study suggests that this could simply be linked to the fact that they were also more likely to get pregnant at an earlier age and could be related to socioeconomic status.
“Worryingly the study did find a significant increase in the chances of having a miscarriage among the women whose mothers had smoked when pregnant with them. ”
The lead author of the paper, Sam Tweed, completed the work as part of his undergraduate degree and graduated from the University of Aberdeen’s Medical School in June.
The research was published in the Human Reproduction Open journal.
Original article – http://www.bbc.com/news/uk-scotland-north-east-orkney-shetland-40593245