Taking the pulse of brain death: A meta-analysis of the natural history of brain death with somatic support.

BACKGROUND AND PURPOSE: The conceptualization of brain death (BD) was pivotal in the shaping of judicial and medical practices. Nonetheless, media reports of alleged recovery from BD reinforced the criticism that this construct is a self-fulfilling prophecy (by treatment withdrawal or organ donation). We meta-analyzed the natural history of BD when somatic support (SS) is maintained. METHODS: Publications on BD were eligible if the following were reported: aggregated data on its natural history with SS; and patient-level data that allowed censoring at the time of treatment withdrawal or organ donation. Endpoints were as follows: rate of somatic expiration after BD with SS; BD misdiagnosis, including "functionally brain-dead" patients (FBD; i.e. after the pronouncement of brain-death, ≥1 findings were incongruent with guidelines for its diagnosis, albeit the lethal prognosis was not altered); and length and predictors of somatic survival. RESULTS: Forty-seven articles were selected (1610 patients, years: 1969-2021). In BD patients with SS, median age was 32.9 years (range = newborn-85 years). Somatic expiration followed BD in 99.9% (95% confidence interval = 89.8-100). Mean somatic survival was 8.0 days (range = 1.6 h-19.5 years). Only age at BD diagnosis was an independent predictor of somatic survival length (coefficient = -11.8, SE = 4, p < 0.01). Nine BD misdiagnoses were detected; eight were FBD, and one newborn fully recovered. No patient ever recovered from chronic BD (≥1 week somatic survival). CONCLUSIONS: BD diagnosis is reliable. Diagnostic criteria should be fine-tuned to avoid the small incidence of misdiagnosis, which nonetheless does not alter the prognosis of FBD patients. Age at BD diagnosis is inversely proportional to somatic survival.

Brain death in pregnancy: a systematic review focusing on perinatal outcomes.

OBJECTIVE: Brain death (BD) during pregnancy might justify in select cases maternal somatic support to obtain fetal viability and maximize perinatal outcome. This study is a systematic review of the literature on cases of brain death in pregnancy with attempt to prolong pregnancy to assess perinatal outcomes. DATA SOURCES: We performed a systematic review of the literature using Ovid MEDLINE, Scopus, PubMed (including Cochrane database), and CINHAIL from inception to April 2020. STUDY ELIGIBILITY CRITERIA: Relevant articles describing any case report of maternal brain death were identified from the aforementioned databases without any time, language, or study limitations. Studies were deemed eligible for inclusion if they described at least 1 case of maternal brain death. METHODS: Only cases of brain death in pregnancy with maternal somatic support aimed at maximizing perinatal outcome were included. Maternal management strategy, diagnosis, clinical course, fetal monitoring, delivery, and fetal and neonatal outcome data were collected. Mean, range, standard deviation, and percentage calculations were used as applicable. RESULTS: After exclusion, 35 cases of brain death in pregnancy were analyzed. The mean gestational age at diagnosis of brain death was at 20.2±5.3 weeks, and most cases (68%) were associated with maternal intracranial hemorrhage, subarachnoid hemorrhage, and hematoma. The most common maternal complications during the study were infections (69%) (eg, pneumonia, urinary tract infection, sepsis), circulatory instability (63%), diabetes insipidus (56%), thermal variability (41%), and panhypopituitarism (34%). The most common indications for delivery were maternal cardiocirculatory instability (38%) and nonreassuring fetal testing (35%). The mean gestational age at delivery was 27.2±4.7 weeks and differed depending on the gestational age at diagnosis of brain death. Most deliveries (89%) were via cesarean delivery. There were 8 cases (23%) of intrauterine fetal demise in the second trimester of pregnancy (14-25 weeks), and 27 neonates (77%) were born alive. Of the 35 cases of brain in pregnancy, 8 neonates (23%) were described as "healthy" at birth, 15 neonates (43%) had normal longer-term follow-up (>1 month to 8 years; mean, 20.3 months), 2 neonates (6%) had neurologic sequelae (born at 23 and 24 weeks of gestation), and 2 neonates (6%) died (born at 25 and 27 weeks of gestation). Mean birth weight was 1,229 grams, and small for gestational age was present in 17% of neonates. The rate of live birth differed by gestational age at diagnosis of brain death: 50% at <14 weeks, 54.5% at 14 to 19 6/7 weeks, 91.7% at 20 to 23 6/7 weeks, 100% at 24 to 27 6/7 weeks, and 100% at 28 to 31 6/7 weeks. CONCLUSION: In 35 cases of brain death in pregnancy at a mean gestation age of 20 weeks, maternal somatic support aimed at maximizing perinatal outcome lasted for about 7 weeks, with 77% of neonates being born alive and 85% of these infants having a normal outcome at 20 months of life. The data of this study will be helpful in counseling families and practitioners faced with such rare and complex cases.

Functional septate junctions between cyst cells are required for survival of transit amplifying male germ cells expressing Bag of marbles.

In adult stem cell lineages, the cellular microenvironment plays essential roles to ensure the proper balance of self-renewal, differentiation and regulated elimination of differentiating cells. Although regulated death of progenitor cells undergoing proliferation or early differentiation is a feature of many tissues, mechanisms that initiate this pruning remain unexplored, particularly in the male germline, where up to 30% of the germline is eliminated before the meiotic divisions. We conducted a targeted screen to identify functional regulators required in somatic support cells for survival or differentiation at early steps in the male germ line stem cell lineage. Cell type-specific knockdown in cyst cells uncovered novel roles of genes in germline stem cell differentiation, including a previously unappreciated role of the Septate Junction (SJ) in preventing cell death of differentiating germline progenitors. Loss of the SJ in the somatic cyst cells resulted in elimination of transit-amplifying spermatogonia by the 8-cell stage. Germ cell death was spared in males mutant for the differentiation factor bam indicating that intact barriers surrounding transit amplifying progenitors are required to ensure germline survival once differentiation has initiated.

The Management of a Thirteen Weeks Pregnant Woman Rendered Brain-Dead Following a Ruptured Aneurysm.

INTRODUCTION: The current lack of clear guidelines on how to manage cases of brain-dead pregnant patients makes this topic controversial and extremely difficult to deal with for both medical and ethical reasons. This report deals with such a situation. CASE PRESENTATION: A twenty-seven years old woman, thirteen weeks pregnant, with a ruptured brain aneurysm was admitted to an Intensive Care Unit. She presented with loss of all brain functions, but somatic support was sustained to enable the delivery of her baby. CONCLUSION: The case report gives a detailed account of the management of the mother before the successful delivery of her baby. It indicates the need for ongoing contributions to the debate on this delicate subject area to establish guidelines on how to manage brain-dead pregnant patients.

Decoding the Regulatory Logic of the Drosophila Male Stem Cell System.

The niche critically controls stem cell behavior, but its regulatory input at the whole-genome level is poorly understood. We elucidated transcriptional programs of the somatic and germline lineages in the Drosophila testis and genome-wide binding profiles of Zfh-1 and Abd-A expressed in somatic support cells and crucial for fate acquisition of both cell lineages. We identified key roles of nucleoporins and V-ATPase proton pumps and demonstrate their importance in controlling germline development from the support side. To make our dataset publicly available, we generated an interactive analysis tool, which uncovered conserved core genes of adult stem cells across species boundaries. We tested the functional relevance of these genes in the Drosophila testis and intestine and found a high frequency of stem cell defects. In summary, our dataset and interactive platform represent versatile tools for identifying gene networks active in diverse stem cell types.

Brain death during pregnancy and prolonged corporeal support of the body: A critical discussion.

AIM: To discuss corporeal support of the brain-dead pregnant woman and to critically examine important aspects of this complex situation that remain as yet unexplored. BACKGROUND: When brain death of the woman occurs during pregnancy, the fetus may be kept inside the corporeally supported body for prolonged periods to enable continued fetal growth and development. This has been increasingly reported in medical literature since 1982 and has received considerable media attention in the past few years. IMPLICATIONS FOR MIDWIVES AND NURSES: Sophisticated advances in medical technologies have altered the boundaries of conception and birth, life and death, Western biomedical and cultural conceptions of women and their bodies, fetal personhood, fetal rights and fetal patienthood, profoundly influencing maternal behaviors, medical decisions and the treatment of pregnant women. This is especially so in the rare, but fraught instance of brain death of the pregnant woman, where nurses and midwives working in High Dependency Care units undertake the daily care of the corporeally supported body that holds a living fetus within it. This discussion enables critical and ethical conversation around the complexities of developing appropriate discourse concerning the woman who suffers brain death during pregnancy and considers the complexities for nurses and midwives caring for the Woman/body/fetus in this context. The potential impact on the fetus of growing and developing inside a 'dead' body is examined, and the absence in the literature of long-term follow up of infants gestated thus is questioned.

Controversy in the Determination of Death: Cultural Perspectives.

The definitions of death have changed throughout recorded history to include not just cardiac death but death by neurological criteria as well. Given the many cultures present in the world, it comes as no surprise that declaring death takes many forms. In the Western world, brain death has gained common acceptance (though not universal), while other cultures and religions have struggled with this issue, especially as it surrounds the controversy of donated organs. There is legal precedent to support death by neurological criteria, as well as support for hospital systems and physicians to terminate somatic support of the brain-dead patient; however, these laws differ greatly from country to country. When dealing with a controversial topic, differing laws, and grief-laden families, it becomes especially crucial that health care staffs are educated regarding varying cultural beliefs surrounding death. In the majority of cases, with kindness and compassion, common ground between science and social perspectives can be found, leading to resolution of care for this group of patients.

Somatic support following cardiac arrest for 90 days leading to a healthy baby boy: A case report.

Due to a lack of published case reports regarding the somatic support of brain dead pregnant patients, each one adds to the limited knowledge that directs care for this patient population. A young woman experienced a cardiac arrest and was subsequently determined to be approximately 20 weeks pregnant following cardio pulmonary resuscitation. Soon after, she was diagnosed as brain dead, but her family chose to keep her supported in hopes of the delivery of a healthy child. She was transferred to our facility, where she was supported after being diagnosed as brain dead for a total of 90 days and delivered a healthy baby boy at almost 32 weeks gestational age. Following delivery, the pregnant patient expired per brain death protocol. The following case report outlines the details of her care and the outcome of our somatic support to share and collaborate with other healthcare professionals caring for this rare patient population.

Healthy baby delivered vaginally from a brain-dead mother.

Case: A pregnant (20 gestational weeks) 32-year-old woman was found in cardiac arrest. Spontaneous circulation returned after 15 min. She became brain dead on the 13th hospital day. The patient was in stable circulatory condition under nasal desmopressin and 20-30 mg/day of hydrocortisone. On the 92nd hospital day at gestational week 33 + 3 days, natural labor began and a healthy 2,130-g girl (Apgar 6/8) was delivered vaginally with minimum assistance. Outcome: The baby was discharged 40 days after birth and followed up regularly. Conclusion: Brain death remains a hopeless condition for patients, but a brain-dead woman may still be able to naturally deliver a healthy baby.

A brain-dead pregnant woman with prolonged somatic support and successful neonatal outcome: A grand rounds case with a detailed review of literature and ethical considerations.

There are increased reports in the medical literature of brain death during pregnancy. In these rare cases, the decision was either to consider discontinuing homeostatic support and mechanical ventilation with an understanding that the fetus then will also die, or to continue full support in an attempt to prolong pregnancy for the purpose of maintaining the fetus alive until maturity. We report the first case in the United Arab Emirates and in literature of somatic support that extended up to 110 days with the successful delivery of a viable fetus. A 35-year-old woman suffered intracranial hemorrhage during the 16(th) week of pregnancy that lead to brain death despite maximal surgical and medical management. Upon confirmation of this diagnosis, the patient received full ventilatory and homeostatic support required to prolong gestation and improve the survival prognosis of her fetus. The status of the patient was discussed in a multidisciplinary approach and with the full involvement of her family. Somatic support continued until the patient was 32 of weeks gestation. Obstetric complications of the patient were frequently assessed and managed. Lower segment cesarean section (LSCS) was then performed. A preterm male in breech presentation was delivered with an average weight of 750 gm, and an Apgar score of 6, 7, and 9 at 1, 5, and 10 minutes, respectively. Prolonging somatic support in a pregnant woman with brain death to allow fetal survival resulted in a successful outcome in terms of saving the life of the fetus. The results are consistent with previous published case reports in the literature on the appropriateness and safety of such a strategy that involved an intensive multidisciplinary approach. Despite being a tragedy, maternal death can represent an opportunity to save the life of the fetus and for organ donation. Consensus future recommendations that can guide the management of similar conditions may also be adapted, especially with the growing medical experience in this context.