SARS-CoV-2 and Placenta: New Insights and Perspectives

The study of SARS-CoV-2 positive pregnant women is of some importance for gynecologists, obstetricians, neonatologists and women themselves. In recent months, new works have tried to clarify what happens at the fetal–placental level in women positive for the virus, and different pathogenesis mechanisms have been proposed. Here, we present the results of a large series of placentas of Coronavirus disease (COVID) positive women, in a reference center for COVID-positive pregnancies, on which we conducted histological, immunohistochemical and electron microscopy investigations. A case–control study was conducted in order to highlight any histopathological alterations attributable to SARS-CoV-2. The prevalence of maternal vascular malperfusion was not significantly different between cases and controls (54.3% vs. 43.7% p = 0.19), whereas the differences with regard to fetal vascular malperfusion (21.1% vs. 4.2% p < 0.001) were significant. More frequent in cases with respect to controls were decidual arteriopathy (40.9% vs. 1.4% p < 0.0001), decidual inflammation (32.4% vs. 0.7% p < 0.0001), perivillous fibrin deposition (36.6% vs. 3.5% p < 0.0001) and fetal vessel thrombi (22.5% vs. 0.7% p < 0.0001). No significant differences in the percentage of terminal villous hyperplasia and chorioamnionitis were observed between the two groups. As the pandemic continues, these studies will become more urgent in order to clarify the possible mechanism of maternal–fetal transmission of the virus.     

Traumatic brain injury and subarachnoid haemorrhage are conditions at high risk for hypopituitarism: screening study at 3 months after the brain injury

OBJECTIVE: Acquired hypopituitarism in adults is obviously suspected in patients with primary hypothalamic-pituitary diseases, particularly after neurosurgery and/or radiotherapy. That brain injuries (BI) can cause hypopituitarism is commonly stated and has been recently emphasized but the management of BI patients does not routinely include neuroendocrine evaluations. AIM: To clarify the occurrence of hypopituitarism in patients after traumatic brain injury (TBI) or subarachnoid haemorrhage (SAH) 3 months after the BI. SUBJECTS AND METHODS: The occurrence of hypopituitarism in conscious patients after traumatic brain injury [TBI, n = 100, 31 women, 69 men; age 37.1 +/- 1.8 years; body mass index (BMI) 23.7 +/- 0.4 kg/m(2); Glasgow Coma Scale (GCS) 3-15] or subarachnoid haemorrhage [SAH, n = 40, 14 men, 26 wpmen, 51.0 +/- 2.0 years; 25.0 +/- 0.6 kg/m(2); Fisher's scale 1-4] was studied in a multicentre study 3 months after the BI. All patients underwent wide basal hormonal evaluation; the GH/IGF-I axis was evaluated by GHRH + arginine test and IGF-I measurement. RESULTS: In TBI patients, some degree of hypopituitarism was shown in 35%. Total, multiple and isolated deficits were present in 4, 6 and 25%, respectively. Diabetes insipidus was present in 4%. Secondary adrenal, thyroid and gonadal deficit was present in 8, 5 and 17%, respectively. Severe GH deficiency (GHD) was the most frequent pituitary defect (25%). In SAH patients, some degree of hypopituitarism was shown in 37.5%. Despite no total hypopituitarism, multiple and isolated deficits were present in 10 and 27.5%, respectively. Diabetes insipidus was present in 7.5%. Secondary adrenal, thyroid and gonadal deficit was present in 2.5, 7.5 and 12.5%, respectively. Severe GHD was the most frequent defect (25%). CONCLUSIONS: TBI and SAH are conditions associated with high risk of acquired hypopituitarism. The pituitary defect is often multiple and severe GHD is the most frequent defect. Thus neuroendocrine evaluations are always mandatory in patients after brain injuries.     

Key elements of preparedness for pandemic coronavirus disease 2019 (COVID-19) in nuclear medicine units

European Journal of Nuclear Medicine and Molecular Imaging -     

A new mutation in GJC2 associated with subclinical leukodystrophy

Recessive mutations in GJC2, the gene-encoding connexin 47 (Cx47), cause Pelizaeus–Merzbacher-like disease type 1, a severe dysmyelinating disorder. One recessive mutation (p.Ile33Met) has been associated with a much milder phenotype––hereditary spastic paraplegia type 44. Here, we present evidence that a novel Arg98Leu mutation causes an even milder phenotype––a subclinical leukodystrophy. The Arg98Leu mutant forms gap junction plaques in HeLa cells comparable to wild-type Cx47, but electrical coupling was 20-fold lower in cell pairs expressing Arg98Leu than for cell pairs expressing wild-type Cx47. On the other hand, coupling between Cx47Arg98Leu and Cx43WT expressing cells did not show such reductions. Single channel conductance and normalized steady-state junctional conductance–junctional voltage (G _j–V _j) relations differed only slightly from those for wild-type Cx47. Our data suggest that the minimal phenotype in this patient results from a reduced efficiency of opening of Cx47 channels between oligodendrocyte and oligodendrocyte with preserved coupling between oligodendrocyte and astrocyte, and support a partial loss of function model for the mild Cx47 associated disease phenotypes.     

Statistical notes. From superiority to non-inferiority clinical trials: a leap in the dark?]

In these "statistical notes", equivalence and non-inferiority randomized controlled clinical trials (RCCT) are considered. Equivalence trials are designed to confirm the absence of a meaningful difference between the effect of two treatments. Non-inferiority trials are designed to prove that the new treatment is no less effective than an existing one: it may be more effective or it may have a similar effect. In this note the attention is addressed to suitable criteria for the choice of the tolerance margin epsilon, i.e. the largest difference which is clinically acceptable, so that a difference bigger than that would matter in practice. In particular, the procedures for the determination of the margin epsilon, used by the authors of the non-inferiority RCCT COBALT and INJECT, are presented and discussed in detail. The ethical implications of equivalence and non-inferiority RCCT are here considered and the reader is repeatedly invited to consider the appropriateness of the basic arguments asserted by the supporters of this kind of studies.     

Cardiotoxicity from Capecitabine Chemotherapy: Prospective Study of Incidence at Rest and During Physical Exercise

BackgroundPhysical activity may increase the risk of cardiotoxicity (myocardial ischemia, major arrhythmias) of 5-Fluorouracil, but this risk has never been investigated for its prodrug capecitabine.Patients and MethodsOne hundred and ninety-two consecutive patients undergoing capecitabine chemotherapy from December 1, 2010 through July 31, 2016 were prospectively evaluated. The baseline evaluation included electrocardiography (ECG) and echocardiography (2DE); a follow-up evaluation, including ECG and exercise stress testing (2DE in case of ECG abnormalities), was done after ≥10 days of treatment. Cardiotoxicity was suspected from ischemic ECG changes, new kinetic abnormalities at 2DE, Lown classification ≥2 ventricular arrhythmia, symptomatic arrhythmias, or positive stress test, and confirmed by a negative stress test after capecitabine washout.ResultsCardiotoxicity was diagnosed in 32 patients (16.7%): six at rest and 26 during exercise. All 32 patients had ECG abnormalities: ST-segment changes (24 patients), negative T-waves (2) and/or arrhythmias: ventricular arrhythmias (14 cases), supraventricular tachycardia (2), complete heart block (1). Eight patients had typical symptoms, 6 had atypical symptoms, 1 had syncope, 17 (53%) were asymptomatic. Cardiotoxicity was more common in patients with atypical symptoms during daily life (OR = 15.7) and in those on a therapeutic schedule of 5 days/week (OR = 9.44).ConclusionCapecitabine cardiotoxicity is frequent, and often elicited by physical effort. Oncologists, cardiologists, and general practitioners should be aware of this risk. Active cardiotoxicity surveillance with ECG (and echocardiogram and/or stress testing in suspected cases) during therapy is recommended.Clinical Trials registration numberCRO-2010-17.     

Long-term outcome of neoadjuvant systemic therapy for locally advanced breast cancer in routine clinical practice

Purpose

The aim of this study is to evaluate the long-term outcome of patients with locally advanced breast cancer treated with neoadjuvant systemic chemotherapy (NST) in routine clinical practice.

Methods

Four hundred and nine patients were identified between January 1999 and December 2011. All patients received NST followed by surgery, adjuvant treatments and radiotherapy, as appropriate.

Results

At Kaplan–Meier analysis, patients with surgical stage III disease were more likely to develop distant metastasis and die from breast cancer (p < 0.001). Luminal A and luminal B/HER2-negative patients had better prognosis; moreover, patients with hormone receptor (HR)-positive tumors had a significantly longer DRFS (p < 0.0049) and OS (p < 0.0001) compared with patients with HR-negative tumors as well as patients who underwent breast-conserving surgery (DRFS and OS: p < 0.001). In multivariate analysis, HR negativity (p < 0.001 for both DRFS and OS), mastectomy (DRFS: p = 0.009; OS: p = 0.05) and stage III disease (DRFS: p < 0.001; OS: p = 0.003) were associated with shorter DRFS and OS.

Conclusions

HR negativity, mastectomy and pathological stage III disease are the variables independently associated with a worse outcome in our cohort of patients. These data are of high interest since they derive from a very heterogeneous group of patients, treated with different neoadjuvant/adjuvant regimens outside of clinical trials and with a long follow-up period.     

Multi-Technique Diagnostic Analysis of Plasters and Mortars from the Church of the Annunciation (Tortorici,Sicily)

Plasters and mortars of the Church of the Annunciation (Tortorici, Sicily) were characterized, for the first time, both at the elemental and molecular levels, by means of portable X-ray fluorescence (XRF) and Raman spectroscopy, to achieve information on the “state of health” of the whole structure. The understanding of their degradation mechanisms and the identification of consequent degradation patterns can define the environmental factors responsible for interpreting the potential pathological forms that can impact the general building vulnerability. In this sense, the results obtained in this article provide relevant information to identify and address both the characterization of building materials and the fundamental causes of their deterioration. At the same time, if coupled with the attempt to supply a chronological order of the major restoration interventions carried out on the investigated site, they provide new insights to calibrate the models for building vulnerability studies.