Calcified uterine leiomyoma from an 18th-century nunnery in North Italy.

OBJECTIVE: To develop a differential diagnosis of a mass retrieved alongside skeletal remains in the crypt of the church of Santissima Annunziata of Valenza (Province of Alessandria, Northern Italy). MATERIAL: A calcified mass measuring 40 × 39 mm and 17.62 × 16.3817.62 × 16.38 mm. METHOD: The analysis utilized macroscopic assessment and histologic examination (including histochemical and immunohistochemical analyses). RESULTS: Morphological traits include an irregular and spongy external surface. Holes of different sizes lead toward the inner part of the object. A section of the mass shows an "intertwined bundle" pattern, confirmed by microscopic examination. CONCLUSIONS: Differential diagnosis determined the mass to be consistent with calcified leiomyoma. SIGNIFICANCE: Identifying uterine leiomyoma adds to the paucity of paleopathological literature on the condition and to calcified tumors more broadly. It also allows for an important discussion of women's gynecological health in the past and potentially among nulliparous women. LIMITATIONS: Neither histochemical staining nor immunohistochemical analysis demonstrated the certain muscular nature of the specimens due to the rehydration and decalcification processes, for which there are no gold standards. SUGGESTIONS FOR FURTHER RESEARCH: Calcified masses are common in the clinical literature but remain rare in paleopathological literature. Careful excavation and improved recognition of apparently calcified masses are necessary to improve recognition, diagnosis, and interpretation.

Pregnancy complications after allogeneic hematopoietic stem cells transplantation: Focus on the placenta.

INTRODUCTION: hematopoietic stem cells transplantation (HSCT) is a treatment option for malignant and non-malignant haematological diseases. Because of the improved survival rates and the more widespread use of reproductive technologies in the last two decades, the number of patients who conceive is increasing while the pathogenesis of some obstetrical complications observed is not yet fully clarified. METHODS: we present complete data about two pregnancies in women who had previously undergone HSTC, with conditioning regimen including total body irradiation. One pregnancy is spontaneous and one after oocytes donation. RESULTS: In both pregnancies we observed relevant intrauterine growth retardation, attributable to a deficit in implantation and placentation. Ultrasound and histological data point to a defective placenta development, possibly sustained by uterine vessel damage caused by irradiation. A deeper understanding of factors influencing placentation post total body irradiation and HSCT, including the possible role of donor's sex and graft versus host disease, is pivotal to improve pregnancy outcomes in this specific population.

A Rare Case of Fatal Thyroid Hemorrhage After Fine-Needle Aspiration: Case Report and Review of the Literature.

ABSTRACT: Sudden death due to massive hemorrhage after a mini-invasive ambulatory diagnostic procedure is extremely rare. Fine-needle aspiration (FNA) of thyroid nodules is very safe, displaying a low rate of complications, all of which mild and often self-limiting. In few cases do these complications necessitate surgical decompression, and rarely does FNA of a thyroid nodule lead to the death of the patient.We report a case of sudden death caused by respiratory insufficiency after compression of the vascular and nervous structures of the neck and obstruction of the upper airways by hemorrhages dissecting the thyroidal and perithyroidal tissues in a 78-year-old woman. These hemorrhages were the result of vascular lacerations caused during diagnostic FNA of a nodule suspected of malignancy. In such cases, it is important to conduct a complete autopsy and histological analysis to ascertain the origin of massive hemorrhage involving the structures of the neck and to attribute the cause of death to the aforementioned procedure. The forensic pathologist must bear in mind that even extremely small damage, such as that produced by a fine needle, may cause a fatal hemorrhage in subjects with a subverted anatomo-pathological picture (such as, for example, the massive fibrosis of an organ).

Placental Characteristics of a Large Italian Cohort of SARS-CoV-2-Positive Pregnant Women.

The variety of placental morphological findings with SARS-CoV-2 maternal infections has raised the issue of poor agreement in histopathological evaluation. The aims of this study were: to describe the histopathological placental features of a large sample of SARS-CoV-2-positive women who gave birth in Italy during the COVID-19 pandemic, to analyse the factors underlying these lesions, and to analyse the impact of placental impairment on perinatal outcomes. From 25 February 2020 to 30 June 2021, experienced perinatal pathologists examined 975 placentas of SARS-CoV-2-positive mothers enrolled in a national prospective study, adopting the Amsterdam Consensus Statement protocol. The main results included the absence of specific pathological findings for SARS-CoV-2 infections, even though a high proportion of placentas showed signs of inflammation, possibly related to a cytokine storm induced by the virus, without significant perinatal consequences. Further research is needed to better define the clinical implications of placental morphology in SARS-CoV-2 infections, but the results of this large cohort suggest that placentas do not seem to be a preferential target for the new Coronavirus infection.

Comparison of Bone-Level and Tissue-Level Implants: A Pilot Study with a Histologic Analysis and a 4-Year Follow-up.

This study clinically and histologically evaluated the performance of implants with different crestal morphologies: tissue-level implants and bone-level implants. Nine patients received at least two adjacent implants in an edentulous area: one bone-level implant (EO) and one tissue-level implant (TG) (total: 23 implants), placed beside each other using a single-stage delayed loading protocol. The implants were rehabilitated with screw-retained fixed partial dentures. Plaque Index (PI), bleeding on probing (BOP), probing depth (PD), and peri-implant bone level were recorded at various postsurgical follow-ups, including 2 and 6 months as well as 1 and 4 years. At 3 months postsurgery, soft tissue biopsy samples were taken from all implant sites and histologically analyzed. Longitudinal assessment of the results (TG vs EO implants) was performed using a linear mixed model with random intercept and by using Spearman correlation or chi-square after visual inspection of the probability distribution. Student t test was used to compare means, and chi-square test was used for dichotomic variables. P < .05 was considered statistically significant. All implants were functional at 4 years. Peri-implant bone resorption was limited, with means of 1.20 ± 0.71 mm and 1.24 ± 0.82 mm for TG and EO implants, respectively. No significant differences in clinical parameters were identified between EO and TG implants. Histologic analysis revealed normal peri-implant soft tissue healing with poor inflammatory infiltrate. Differences in the histologic appearance of soft tissues were more related to patients than implant type. Both implants appeared to be suitable for partial rehabilitation of edentulous arches without differences in the investigated clinical and histologic parameters. However, TG implants showed a greater risk of implant collar exposure.

Sudden Onset of Severe Pulmonary Hypertension in a Preterm Infant: A Case Report on the Role of Maternal Use of Serotonin Re-Uptake Inhibitors During Pregnancy and Concurrent Risk Factors.

Persistent pulmonary hypertension of the newborn (PPHN) is a severe condition caused by failed circulatory adaptation at birth. Pulmonary hypertension is most common in full-term infants and rare in preterms, although it is increasingly diagnosed also in extremely preterm infants. Previous studies demonstrated the association between maternal use of selective serotonin re-uptake inhibitors during gestation and pulmonary hypertension. This brief report describes the complex physiopathological correlations that were identified in a case of severe pulmonary hypertension in a fetal growth restricted (FGR) preterm infant, with a history of maternal use of antidepressants during pregnancy. Perinatal factors, triggers and aggravating mechanisms caused a dramatic clinical course. Maternal history of escitalopram therapy throughout pregnancy was noted. Uteroplacental insufficiency, fetal hypoxia, FGR, preeclampsia, preterm delivery, antenatal steroids, and cesarean section were documented as concurrent risk factors. Myocardial immaturity and dysfunction, secondary to FGR and prematurity aggravated the hemodynamic compromise. The short time gap between pharmacological ductal closure and the onset of PPHN may suggest a cause-effect relationship, as observed in previous reports. Placental histopathologic findings are reported.

Proteomic profiling of human amnion for preterm birth biomarker discovery.

Spontaneous preterm birth (PTB) complicates about 12% of pregnancies worldwide, remaining the main cause of neonatal morbidity and mortality. Spontaneous preterm birth PTBs is often caused by microbial-induced preterm labor, mediated by an inflammatory process threatening both maternal and newborn health. In search for novel predictive biomarkers of PTB and preterm prelabor rupture of the membranes (pPROM), and to improve understanding of infection related PTB, we performed an untargeted mass spectrometry discovery study on 51 bioptic mid zone amnion samples from premature babies. A total of 6352 proteins were identified. Bioinformatics analyses revealed a ranked core of 159 proteins maximizing the discrimination between the selected clinical stratification groups allowing to distinguish conditions of absent (FIR 0) from maximal Fetal Inflammatory Response (FIR 3) stratified in function of Maternal Inflammatory Response (MIR) grade. Matrix metallopeptidase-9 (MMP-9) was the top differentially expressed protein. Gene Ontology enrichment analysis of the core proteins showed significant changes in the biological pathways associated to inflammation and regulation of immune and infection response. Data suggest that the conditions determining PTB would be a transversal event, secondary to the maternal inflammatory response causing a breakdown in fetal-maternal tolerance, with fetal inflammation being more severe than maternal one. We also highlight matrix metallopeptidase-9 as a potential predictive biomarker of PTB that can be assayed in the maternal serum, for future investigation.

L1CAM variants cause two distinct imaging phenotypes on fetal MRI.

Data on fetal MRI in L1 syndrome are scarce with relevant implications for parental counseling and surgical planning. We identified two fetal MR imaging patterns in 10 fetuses harboring L1CAM mutations: the first, observed in 9 fetuses was characterized by callosal anomalies, diencephalosynapsis, and a distinct brainstem malformation with diencephalic-mesencephalic junction dysplasia and brainstem kinking. Cerebellar vermis hypoplasia, aqueductal stenosis, obstructive hydrocephalus, and pontine hypoplasia were variably associated. The second pattern observed in one fetus was characterized by callosal dysgenesis, reduced white matter, and pontine hypoplasia. The identification of these features should alert clinicians to offer a prenatal L1CAM testing.

Multidisciplinary study of sudden unexpected infant death in Liguria (Italy): a nine-year report.

INTRODUCTION: We conducted a retrospective analysis of cases of sudden unexpected infant death (SUID) referred to the SIDS-ALTE Center of the Liguria Region (Italy) from 2010 to 2018. In all cases, the death scene was inspected, and a multidisciplinary post-mortem evaluation was conducted. Our aim was to analyze the epidemiological data and etiological distribution. EVIDENCE ACQUISITION: We examined 15 cases initially classified as sudden infant death. EVIDENCE SYNTHESIS: In all cases, the death was initially unexplained. Seven cases involved males and eight involved females. Their mean age was 67.47 days; the youngest victim was 2 days old, while the oldest was 8.5 months (253 days). In 7 cases, the post-mortem analysis showed an infection of lung. In 4 cases, the prone position of the infant during sleep was identified as a risk factor. Only in one case the cause of death remains unexplained, and it was classified as sudden infant death syndrome II according to San Diego Classification. CONCLUSIONS: In the forensic approach to cases of SUID, it is always important to conduct a thorough multidisciplinary investigation. In order to avoid procedural errors that might compromise the post-mortem investigation, it is necessary to consider the medical and social history of both mother and child, in addition to the circumstances of the death. Moreover, a complete pediatric post-mortem examination and multidisciplinary discussion are required in order to identify potentially important causative or contributory factors.

Sudden and unexpected death in childhood due to an undiagnosed hepatoblastoma: Case report and review of literature.

The sudden and unexpected death of an infant or child due to cancer is a particularly rare event. Most of the cases concern primary growths located in vital organs such as the heart or the brain. Only in an extremely small number of cases does it occur in infants or children affected by liver cancer. Herein we report the sudden and unexpected death of a 3-and-a-half-year-old infant, who due to an undiagnosed tumor of the liver, namely hepatoblastoma, suffered a major intra-abdominal (hemoperitoneum) bleed, leading to a fatal hemorrhagic trauma. In cases like these, it is of utmost importance to carry out both an autopsy as well as complete histological tests in order to determine if the hepatic tumor is the real cause of death or if it was a mere chance finding. In the case of sudden and unexplained deaths in infancy and childhood, the forensic pathologist should always consider that other complications, for example, those correlated with hepatoblastoma could, in fact, cause sudden death given that this particular tumor is often scarcely symptomatic and can remain undiscovered for a long period of time.

Complications related to in vitro reproductive techniques support the implementation of natural procreative technologies.

BACKGROUND AND AIM: Infertility affects ~20% of the couples in the world. Assisted reproductive technologies (ARTs) are currently the most common treatment option for infertility. Nevertheless, ARTs may be associated with complications for mothers and/or offspring. Natural procreative technology (NaProTechnology) is a natural treatment which minimizes these risks by seeking to identify the causes of infertility to enable better treatments. This narrative review summarizes the complications related to ARTs and clarifies how the NaProTechnology approach can help ARTs to achieve better results or be used in alternative to ARTs. METHODS: Data in the literature indicate that NaProTechnology is a natural approach for treating infertility. RESULTS: The percentage of live births obtained by NaProTechnology is similar to that of ARTs. CONCLUSIONS: An extensive search for the genetic defects causing infertility or subfertility through genetic testing can help both ARTs and NaProTechnology to achieve successful pregnancies. By discovering the underlying causes of infertility, genetic tests enable better family counseling, like the implications of transmitting risk- and disease-alleles to future generations.

Prenatal genetic diagnosis: Fetal therapy as a possible solution to a positive test.

BACKGROUND: Fetal abnormalities cause 20% of perinatal deaths. Advances in prenatal genetic and other types of screening offer great opportunities for identifying high risk pregnancies. METHODS: Through a literature search, here we summarise what are the prenatal diagnostic technique that are being used and how those techniques may allow for prenatal interventions. RESULTS: Next generation sequencing and non-invasive prenatal testing are fundamental for clinical diagnostics because of their sensitivity and accuracy in identifying point mutations, aneuploidies, and microdeletions, respectively. Timely identification of genetic disorders and other fetal abnormalities enables early intervention, such as in-utero gene therapy, fetal drug therapy and prenatal surgery. CONCLUSION: Prenatal intervention is mainly focused on conditions that may cause death or lifelong disabilities, like spina bifida, congenital diaphragm hernia and sacrococcygeal teratoma; and may be an alternative therapeutic option to termination of pregnancy. However, it is not yet widely available, due to lack of specialized centers.

Placental Pathology Findings and the Risk of Intraventricular and Cerebellar Hemorrhage in Preterm Neonates.

Placental pathology as a predisposing factor to intraventricular hemorrhage remains a matter of debate, and its contribution to cerebellar hemorrhage development is still largely unexplored. Our study aimed to assess placental and perinatal risk factors for intraventricular and cerebellar hemorrhages in preterm infants. This retrospective cohort study included very low-birth weight infants born at the Gaslini Children's Hospital between January 2012 and October 2016 who underwent brain magnetic resonance with susceptibility-weighted imaging at term-equivalent age and whose placenta was analyzed according to the Amsterdam Placental Workshop Group Consensus Statement. Of the 286 neonates included, 68 (23.8%) had intraventricular hemorrhage (all grades) and 48 (16.8%) had a cerebellar hemorrhage (all grades). After correction for gestational age, chorioamnionitis involving the maternal side of the placenta was found to be an independent risk factor for developing intraventricular hemorrhage, whereas there was no association between maternal and fetal inflammatory response and cerebellar hemorrhage. Among perinatal factors, we found that intraventricular hemorrhage was significantly associated with cerebellar hemorrhage (odds ratio [OR], 8.14), mechanical ventilation within the first 72 h (OR, 2.67), and patent ductus arteriosus requiring treatment (OR, 2.6), whereas cesarean section emerged as a protective factor (OR, 0.26). Inotropic support within 72 h after birth (OR, 5.24) and intraventricular hemorrhage (OR, 6.38) were independent risk factors for cerebellar hemorrhage, whereas higher gestational age was a protective factor (OR, 0.76). Assessing placental pathology may help in understanding mechanisms leading to intraventricular hemorrhage, although its possible role in predicting cerebellar bleeding needs further evaluation.

Unexpected and Sudden Death Due to Undiagnosed Moraxella catarrhalis Meningoencephalitis in a 40-day-old Infant: Case Report and Literature Review.

Acute bacterial meningitis in infants and newborns represents a medical emergency and a significant cause of mortality and morbidity worldwide. Moraxella catarrhalis has been considered a microorganism with low pathogenic potential, and only in exceptional cases has it been found to cause meningitis in infants and immunocompetent people. We will now document an unusual case of an unexpected and sudden death of a 40-day-old infant due to acute meningitis from M. catarrhalis, apparently asymptomatic and subsequently diagnosed by an autopsy. According to our knowledge this is the first case of unexpected infant death due to undiagnosed M. catarrhalis meningitis.The suggested case, as well as for the rarity of such a fatal event, should be considered a caution to pediatrics and neonatologists for M. catarrhalis can cause paucisymptomatic meningoencephalitis in infants which can be potentially fatal.From a forensic point of view, an autopsy accompanied by a multidisciplinary assessment is always necessary in cases of unexpected infant deaths to identify the causes.

Loss of Wwox Perturbs Neuronal Migration and Impairs Early Cortical Development.

Mutations in the WWOX gene cause a broad range of ultra-rare neurodevelopmental and brain degenerative disorders, associated with a high likelihood of premature death in animal models as well as in humans. The encoded Wwox protein is a WW domain-containing oxidoreductase that participates in crucial biological processes including tumor suppression, cell growth/differentiation and regulation of steroid metabolism, while its role in neural development is less understood. We analyzed the exomes of a family affected with multiple pre- and postnatal anomalies, including cerebellar vermis hypoplasia, severe neurodevelopmental impairment and refractory epilepsy, and identified a segregating homozygous WWOX mutation leading to a premature stop codon. Abnormal cerebral cortex development due to a defective architecture of granular and molecular cell layers was found in the developing brain of a WWOX-deficient human fetus from this family. A similar disorganization of cortical layers was identified in lde/lde rats (carrying a homozygous truncating mutation which disrupts the active Wwox C-terminal domain) investigated at perinatal stages. Transcriptomic analyses of Wwox-depleted human neural progenitor cells showed an impaired expression of a number of neuronal migration-related genes encoding for tubulins, kinesins and associated proteins. These findings indicate that loss of Wwox may affect different cytoskeleton components and alter prenatal cortical development, highlighting a regulatory role of the WWOX gene in migrating neurons across different species.

Natural small molecules as inhibitors of coronavirus lipid-dependent attachment to host cells: a possible strategy for reducing SARS-COV-2 infectivity?

BACKGROUND: Viral infectivity depends on interactions between components of the host cell plasma membrane and the virus envelope. Here we review strategies that could help stem the advance of the SARS-COV-2 epidemic. METHODS AND RESULTS: We focus on the role of lipid structures, such as lipid rafts and cholesterol, involved in the process, mediated by endocytosis, by which viruses attach to and infect cells. Previous studies have shown that many naturally derived substances, such as cyclodextrin and sterols, could reduce the infectivity of many types of viruses, including the coronavirus family, through interference with lipid-dependent attachment to human host cells. CONCLUSIONS: Certain molecules prove able to reduce the infectivity of some coronaviruses, possibly by inhibiting viral lipid-dependent attachment to host cells. More research into these molecules and methods would be worthwhile as it could provide insights the mechanism of transmission of SARS-COV-2 and, into how they could become a basis for new antiviral strategies.