Vertical Transmission of SARS-CoV-2 in Second Trimester Associated with Severe Neonatal Pathology

The effects of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in women on the gestation course and the health of the fetus, particularly in the first and second trimesters, remain very poorly explored. This report describes a case in which the normal development of pregnancy was complicated immediately after the patient had experienced Coronavirus disease 2019 (COVID-19) at the 21st week of gestation. Specific conditions included critical blood flow in the fetal umbilical artery, fetal growth restriction (1st percentile), right ventricular hypertrophy, hydropericardium, echo-characteristics of hypoxic-ischemic brain injury (leukomalacia in periventricular area) and intraventricular hemorrhage at the 25th week of gestation. Premature male neonate delivered at the 26th week of gestation died after 1 day 18 h due to asystole. The results of independent polymerase chain reaction (PCR), mass spectrometry and immunohistochemistry analyses of placenta tissue, umbilical cord blood and child blood jointly indicated vertical transmission of SARS–CoV-2 from mother to the fetus, which we conclude to be the major cause for the development of maternal vascular malperfusion in the studied case.     

Structure-Based Neuron Retrieval Across Drosophila Brains

Comparing local neural structures across large sets of examples is crucial when studying gene functions, and their effect in the Drosophila brain. The current practice of aligning brain volume data to a joint reference frame is based on the neuropil. However, even after alignment neurons exhibit residual location and shape variability that, together with image noise, hamper direct quantitative comparison and retrieval of similar structures on an intensity basis. In this paper, we propose and evaluate an image-based retrieval method for neurons, relying on local appearance, which can cope with spatial variability across the population. For an object of interest marked in a query case, the method ranks cases drawn from a large data set based on local neuron appearance in confocal microscopy data. The approach is based on capturing the orientation of neurons based on structure tensors and expanding this field via Gradient Vector Flow. During retrieval, the algorithm compares fields across cases, and calculates a corresponding ranking of most similar cases with regard to the local structure of interest. Experimental results demonstrate that the similarity measure and ranking mechanisms yield high precision and recall in realistic search scenarios.     

Prognostic factors and efficacy of different chemotherapeutic regimens in patients with mediastinal nonseminomatous germ cell tumors

Purpose

Patients (pts) with mediastinal nonseminomatous germ cell tumors (MNGCT) are belonged to poor prognostic group by IGCCCG. We retrospectively studied the prognostic factors and efficacy of different chemotherapeutic regimen in pts with MNGCT.

Methods

We analyzed data on 61 pts with MNGCT. Conditional induction chemotherapy BEP was performed in 38 %, TBEP—in 28 %, CBOP—in 28 %, accelerated (two weekly) version of BEP—in 6 % pts. Based on similar efficacy of CBOP and TBEP regimens, we combines pts with CPOB and TBEP regimen in one group—55.8 % and different variants of BEP regimen in the second group—44.2 %. Multivariate Cox regression analysis was performed to determine independent factors, which influenced on overall survival.

Results

We revealed the following independent negative prognostic factors: age ≥24 years (p = 0.07), size of the primary mediastinal tumor ≥19 cm (p = 0.03). Median overall survival (OS) has not been reached, and 2-year OS was 66 % in pts with good prognosis (age <24 years and/or size of mediastinal tumor <19 cm) versus 15 months and 40 % in pts with poor prognosis (p = 0.03). Objective marker negative response was revealed more often in pts with CPOB/TBEP group: 26/34 (76.5 %) versus 14/27 (52 %), p = 0.08. Median OS was also higher in pts with CPOB/TBEP group: nonreached versus 15 months (p = 0.01).

Conclusion

CPOB and TBEP regimen were significantly associated with better outcome in pts with MNGCT. Age ≥24 years and size of the primary mediastinal tumor ≥19 cm were found as independent negative prognostic factors.     

The prognostic significance of early treatment response in pediatric relapsed acute myeloid leukemia: results of the international study Relapsed AML 2001/01

The prognostic significance of early response to treatment has not been reported in relapsed pediatric acute myeloid leukemia. In order to identify an early and easily applicable prognostic factor allowing subsequent treatment modifications, we assessed leukemic blast counts in the bone marrow by morphology on days 15 and 28 after first reinduction in 338 patients of the international Relapsed-AML2001/01 trial. Both day 15 and day 28 status was classified as good (≤20% leukemic blasts) in 77% of patients. The correlation between day 15 and 28 blast percentages was significant, but not strong (Spearman correlation coefficient = 0.49, P<0.001). Survival probability decreased in a stepwise fashion along with rising blast counts at day 28. Patients with bone marrow blast counts at this time-point of ≤5%, 6–10%, 11–20% and >20% had 4-year probabilities of survival of 52%±3% versus 36%±10% versus 21%±9% versus 14%±4%, respectively, P<0.0001; this trend was not seen for day 15 results. Multivariate analysis showed that early treatment response at day 28 had the strongest prognostic significance, superseding even time to relapse (< or ≥12 months). In conclusion, an early response to treatment, measured on day 28, is a strong and independent prognostic factor potentially useful for treatment stratification in pediatric relapsed acute myeloid leukemia. This study was registered with ISRCTN code: 94206677.     

Prekallikrein inhibits innate immune signaling in the lung and impairs host defense during pneumosepsis in mice

Prekallikrein (PKK, also known as Fletcher factor and encoded by the gene KLKB1 in humans) is a component of the contact system. Activation of the contact system has been implicated in lethality in fulminant sepsis models. Pneumonia is the most frequent cause of sepsis. We sought to determine the role of PKK in host defense during pneumosepsis. To this end, mice were infected with the common human pathogen Klebsiella pneumoniae via the airways, causing an initially localized infection of the lungs with subsequent bacterial dissemination and sepsis. Mice were treated with a selective PKK-directed antisense oligonucleotide (ASO) or a scrambled control ASO for 3 weeks prior to infection. Host response readouts were determined at 12 or 36 h post-infection, including genome-wide messenger RNA profiling of lungs, or mice were followed for survival. PKK ASO treatment inhibited constitutive hepatic Klkb1 mRNA expression by >80% and almost completely abolished plasma PKK activity. Klkb1 mRNA could not be detected in lungs. Pneumonia was associated with a progressive decline in PKK expression in mice treated with control ASO. PKK ASO administration was associated with a delayed mortality, reduced bacterial burdens, and diminished distant organ injury. While PKK depletion did not influence lung pathology or neutrophil recruitment, it was associated with an upregulation of multiple innate immune signaling pathways in the lungs already prior to infection. Activation of the contact system could not be detected, either during infection in vivo or at the surface of Klebsiella in vitro. These data suggest that circulating PKK confines pro-inflammatory signaling in the lung by a mechanism that does not involve contact system activation, which in the case of respiratory tract infection may impede early protective innate immunity. © 2019 Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.