Histology Atlas of the Developing Mouse Placenta

The use of the mouse as a model organism is common in translational research. This mouse–human similarity holds true for placental development as well. Proper formation of the placenta is vital for development and survival of the maturing embryo. Placentation involves sequential steps with both embryonic and maternal cell lineages playing important roles. The first step in placental development is formation of the blastocyst wall (approximate embryonic days [E] 3.0-3.5). After implantation (∼E4.5), extraembryonic endoderm progressively lines the inner surface of the blastocyst wall (∼E4.5-5.0), forming the yolk sac that provides histiotrophic support to the embryo; subsequently, formation of the umbilical vessels (∼E8.5) supports transition to the chorioallantoic placenta and hemotrophic nutrition. The fully mature (“definitive”) placenta is established by ∼E12.5. Abnormal placental development often leads to embryonic mortality, with the timing of death depending on when placental insufficiency takes place and which cells are involved. This comprehensive macroscopic and microscopic atlas highlights the key features of normal and abnormal mouse placental development from E4.5 to E18.5. This in-depth overview of a transient (and thus seldom-analyzed) developmental tissue should serve as a useful reference to aid researchers in identifying and describing mouse placental changes in engineered, induced, and spontaneous disease models.

The Cross-sectional Average Inequality in Lifespan (CAL†): A Lifespan Variation Measure That Reflects the Mortality Histories of Cohorts

Lifespan variation is a key metric of mortality that describes both individual uncertainty about the length of life and heterogeneity in population health. We propose a novel and timely lifespan variation measure, which we call the cross-sectional average inequality in lifespan, or CAL†. This new index provides an alternative perspective on the analysis of lifespan inequality by combining the mortality histories of all cohorts present in a cross-sectional approach. We demonstrate how differences in the CAL† measure can be decomposed between populations by age and cohort to explore the compression or expansion of mortality in a cohort perspective. We apply these new methods using data from 10 low-mortality countries or regions from 1879 to 2013. CAL† reveals greater uncertainty in the timing of death than the period life table–based indices of variation indicate. Also, country rankings of lifespan inequality vary considerably between period and cross-sectional measures. These differences raise intriguing questions as to which temporal dimension is the most relevant to individuals when considering the uncertainty in the timing of death in planning their life courses.

The cross-sectional average inequality in lifespan (CAL†): A lifespan variation measure that reflects the mortality histories of cohorts

Lifespan variation is a key metric of mortality that describes both individual uncertaintyabout the length of life and heterogeneity in population health. We propose a novel andtimely lifespan variation measure, which we call the Cross-sectional Average Inequality in Lifespan. This new index provides an alternative perspective on the analysis of lifespan inequality by combining the mortality histories of all cohorts present in a cross-sectional approach. We demonstrate how differences in the Cross-sectional Average Inequality in Lifespan measure can be decomposed between populations by age and cohort to explore the compression or expansion of mortality in a cohort perspective. We apply these new methods using data from ten low-mortality countries from 1879 to 2013. The Cross-sectional Average Inequality in Lifespan measure reveals greater uncertainty in the timing of death than the period life table-based indices of variation indicate. Also, country rankings of lifespan inequality vary considerably between period and cross-sectional measures. These differences open intriguing questions as to which temporal dimension is the most relevant to individuals when considering the uncertainty in the timing of death in planning their life courses.

Timing and Causes of Death in Severe COVID-19 Patients

Introduction: Although early identified as a deadly infectious disease, the precise mortality rate of the most severe forms of COVID-19 is a matter of debate. To the best of our knowledge, no study investigated so far, the causes that ultimately led to death as well as the relation between timing and causes of death.Material & Methods: We performed a retrospective study in eight ICU within eight French hospitals. All consecutive adult patients (aged≥ 18 years old) admitted in the ICU with a PCR-confirmed SARS-CoV-2 infection and acute respiratory failure were included in the analysis. Causes and timing of death were reported based on medical records. A binomial logistic regression statistical analysis was performed to identify the determinants associated with ICU-mortality.Results: From March 1st, 2020 to April 28th, 287 patients were admitted to ICU for SARS-CoV-2 related acute respiratory failure. COVID-19 related multiple organ dysfunction syndromes (MODS) was the leading cause of death (29%, n=27/93). End-of-life decisions occurred in 25% of patients (n=23/93). Secondary infections-related MODS accounted for 21% of ICU death, with a majority of ventilator-associated pneumonia. Fatal ischemic events (venous or arterial) occurred in 12% of patients. Refractory hypoxemia was a relatively uncommon cause of death and occurred only in 8 cases (9%). Regarding the timing of death, only one death occurred during the first three days of ICU admission. Determinants associated with ICU-mortality in logistic regression were age >65, requirement for vasopressors, renal replacement therapy and extracorporeal membrane oxygenation.Conclusion: Our data suggest the existence of a specific pattern of outcome in severe COVID-19 patients compared to severe bacterial and viral pneumonia, consisting in a high proportion of delayed COVID-19 related MODS.

Survival and causes of death in extremely preterm infants in the Netherlands

ObjectiveIn the Netherlands, the threshold for offering active treatment for spontaneous birth was lowered from 25+0 to 24+0 weeks’ gestation in 2010. This study aimed to evaluate the impact of guideline implementation on survival and causes and timing of death in the years following implementation.DesignNational cohort study, using data from the Netherlands Perinatal Registry.PatientsThe study population included all 3312 stillborn and live born infants with a gestational age (GA) between 240/7 and 266/7 weeks born between January 2011 and December 2017. Infants with the same GA born between January 2007 and December 2009 (N=1400) were used as the reference group.Main outcome measuresSurvival to discharge, as well as cause and timing of death.ResultsAfter guideline implementation, there was a significant increase in neonatal intensive care unit (NICU) admission rate for live born infants born at 24 weeks’ GA (27%–69%, p<0.001), resulting in increased survival to discharge in 24-week live born infants (13%–34%, p<0.001). Top three causes of in-hospital mortality were necrotising enterocolitis (28%), respiratory distress syndrome (19%) and intraventricular haemorrhage (17%). A significant decrease in cause of death either complicated or caused by respiratory insufficiency was seen over time (34% in 2011–2014 to 23% in 2015–2017, p=0.006).ConclusionsImplementation of the 2010 guideline resulted as expected in increased NICU admissions rate and postnatal survival of infants born at 24 weeks’ GA. In the years after implementation, a shift in cause of death was seen from respiratory insufficiency towards necrotising enterocolitis and sepsis.

Timing of death of a dead born foetus determined at medico-legal autopsy refuted the allegation of medical negligence

The case concerns a dead newborn. The family alleged that his death was due to delay in delivery by the attending doctors. Medico-legal autopsy was performed three days later which showed maceration changes suggestive of the foetus lying dead-in-utero for about 24 h which prima facie refuted the allegation of negligence.